Brands

Brands and products that show up often enough to matter to the scene map.

Reference Index

Use the title to open the reference entry. Use the caret to expand a compact inline dossier with source context, issue trail, related pages, and outbound links.

Tesla

Tesla is a recurring brand in the Astral Codex Ten archive, appearing 24 times across 24 issues between January 28, 2021 and July 01, 2025. The archive places it in contexts such as "Your doctor makes $200,000/year and drives a Tesla"; "Developed by Tesla's self-driving-car division"; "Point B is Tesla, making revolutionary new environmentally-friendly cars". It most often appears alongside Elon Musk, Twitter, SpaceX.

Article page
Tesla
Mention count
24
Issue count
24
First seen
January 28, 2021
Last seen
July 01, 2025
January 28, 2021 · Original source
Suppose you make the US median income of $36,000/year. You live in an average American town where you see people of various social strata. Your doctor makes $200,000/year and drives a Tesla. Your sister is a single mother making $20,000/year, and needs food stamps to make ends meet. You probably think you have a good sense of class distinctions.
February 12, 2021 · Original source
Driverify: Developed by Tesla's self-driving-car division. Cars mine Driverify with spare computing power while idling, and spend it bidding against each other for right-of-way if they arrive at a four-way stop sign at the same time (users can preprogram how aggressively their cars bid in these auctions). Compatible Teslas would also have fenders that send electrical pulses, transmitting data into the receiver fender of another car. If two Teslas got in a fender-bender, they could use their now-connected fenders to have the at-fault car recompense the victim by transferring an appropriate amount of Driverify.
March 25, 2021 · Original source
What about Distribution 2? Now Point B is Tesla, making revolutionary new environmentally-friendly cars. In fact, let's say it's some super-Tesla that's even better than the real Tesla, plus their cars are affordable even for the poorest people. Point A is Yugo (or if you know a more modern example of a terrible car company, use that). Now which distribution would you rather have?
Distribution 2, definitely! You can buy the super-Tesla and be very happy, without ever worrying about Yugo. In fact, after a few years Yugo will go out of business, super-Tesla will dominate the market, and everyone will be very happy.
Diversity libertarianism is usually in favor of companies being allowed to do a wide range of things, because it ensures everyone will be well-served. If you assume an arbitrarily large number of uncorrelated companies, then whatever the thing you want is, there's at least one existing or easy-to-start company doing it. If Ford refuses to sell cars to black people, Toyota should see a profit opportunity and step in. If both Ford and Toyota ban blacks at the same time, some upstart like Tesla should step in. If Ford, Toyota, and Tesla all do it, some guy with a wrench who's always dreamed of making cars in his garage should notice a billion-dollar business opportunity lying on the ground, get seed capital from equally greedy investors, and solve the problem.
April 16, 2021 · Original source
Although 2021 seems better than 1879 in absolute material terms, George's complaint still rings true: healthcare and higher education are increasingly unaffordable, inequality is as bad as it ever was, and The Rent Is Too Damn High. And even if all of these measures had improved as well, we still have to contend with a fundamental complaint: how can human civilization have piled up an amount of wealth best described as absolutely banana pants insane, and yetstill have poverty, oppression and cyclical recessions? Yes, greed, evil, and human nature will always be with us, but isn't it weird that we haven't eliminated these economic problems the same way we've eliminated Smallpox, Scurvy, and having to write your scathing polemics about Thomas Jefferson by candlelight with a goose feather? Giving the mic back to George, he closes the chapter with this haunting quote, first written 142 years ago: If there is less deep poverty in San Fran Francisco than in New York, is it not because San Francisco is yet behind new York in all that both cities are striving for? When San Francisco reaches the point where New York now is, who can doubt that there will also be ragged and barefooted children on her streets? I'll just leave this here: Number of Homeless Children in U.S. At All-Time High; California Among Worst States. I. Wages and Capital George insists sloppy terminology leads to sloppy thinking. Naturally, he spends an entire chapter beating words to death to correct this. The Meaning of the Terms Let's start with Wealth. The common usage, both then and now, is "anything with an exchange value." George doesn't like how this mixes dissimilar things. By George, what is wealth? Wealth is produced when Nature's bounty is touched by human labor resulting in a tangible product that is the object of human desire. Labor is required, but the amount and type doesn't matter - George offers the example of simply picking a berry off a bush as an act that transforms nature's gifts into human wealth. Note particularly that human desire is an important requirement of wealth; it doesn't matter how much work someone put into something, if it doesn't gratify human needs or desires in some way, it's not wealth. Speaking of human desire, let's talk about Value. Where does a thing's value come from? The prevailing theory of the day was the Labor Theory of Value which originated with Adam Smith and David Ricardo, which says that Labor is the source of value. The early formulations were a bit ambiguous, here's Smith in Wealth of Nations for instance: The value of any commodity ... is equal to the quantity of labor which it enables him to purchase or command. Labor, therefore, is the real measure of the exchangeable value of all commodities. So... is a thing's value how much labor it takes to make the thing, or how much labor someone's willing to exchange for the thing? Nowadays Labor Theory of Value is most commonly associated with Marx. Marx picks a lane and says the value of something is tied to the amount of "socially necessary labor" required to produce it. George goes the other way: It is never the amount of labor that has been exerted in bringing a thing into being that determines its value, but always the amount of labor that will be rendered in exchange for it. - Henry George, The Science of Political Economy, p. 253 In other words, "a thing's value is whatever someone is willing to pay for it." This is in line with the so-called marginal revolution (the movement, not the blog) and modern theories of value. Labor Labor is the exertion of human beings. It's possible to labor to no avail (try punching a concrete wall), but typically humans labor towards an end, such as gaining wealth. But whether or not we accomplish anything with our efforts, George calls them labor. Labor isn't just making things, by the way – it's also moving or exchanging them. Production Production is labor applied "to the production of wealth." You know, productively. This is all human exertion that isn't punching a concrete wall and rewards you for your efforts with something that fits the definition of wealth. Said wealth is the "product of labor." Wages whatever is received as the result or reward of exertion is "wages." No distinction here is made between blue-collar work and white-collar work – whether one is called "hourly pay" and the other is called "annual salary," George calls them both "wages." It doesn't matter whether you receive them from your boss, from customers, or from nature. If you do work and get something from it, you have received "wages." With those basics under our belt, let's circle back to Wealth: What are some examples of wealth? By George, Gold is wealth. Teddy bears are wealth. Tesla roadsters and candy canes and young adult vampire romance novels are wealth. The same goes for fish you've caught, deer you've hunted, and cool looking rocks you've picked up on your morning walk. The value of these things may differ, but as long as they're tangible, originate in nature, someone ever did a lick of work to make or acquire them, and a human being somewhere desires them for any reason, they're wealth. It gets a little clearer when we ask what isn't wealth. And by George, Money isn't wealth. Articles of gold are wealth because they're tangible things that have been dug up, crafted, and fulfill certain human desires. But paper currency, digital currencies, and other things that aren't inherently valuable but merely represent value are not wealth (outside of putting their physical articles in coin collections or making paper airplanes, and so forth). Now don't get the man wrong, these things are certainly valuable. They're just not wealth. They are certificates that represent claims on wealth. For any computer programmers in the audience, money is a pointer to wealth. Likewise Stocks and Bonds and other financial instruments are not wealth. These are also just claims on wealth. A creditor's title to Debt isn't wealth, either, it's just a claim on the debtor's (typically future) wealth. And, writing as he was not long after the Civil War, George points out that Slaves are not wealth either but, represent "merely the power of one class to appropriate the earnings of another class." Wealth, thus defined, is the terminal "ground truth" bits of the economy, and all the financial layers on top are fancy IOUs that just encode various claims on it. George offers a thought experiment to test if something is wealth: if you produce a pile of gold, fish, or Lego bricks, you've clearly increased the amount of wealth in the world. But if you produce a giant pile of IOUs that just records who owns what and who owes what to whom, it doesn't matter how many of them you pile up or how long the chains of ownership get, you still haven't increased the amount of real wealth in the world. Again, this isn't saying the IOUs aren't valuable, they are. But they're only valuable because they ultimately point to real wealth. If you magically transported everyone over to a hypothetical Earth 2, carrying over all of Earth 1's money and financial instruments but none of Earth 1's tangible wealth, the value of all those IOUs would instantly evaporate. Now what about digital goods? Leaving things like Bitcoin aside for the moment, let's consider the case of a digital image file: By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
April 19, 2021 · Original source
For a dose of cold water, see Investing in Technological Revolutions by Ben Felix. Remember, it's not how much a sector grows that makes it a good investment so much as how much it grows relative to what you paid for it. The highest return on investment stock of all time hasn't been Google, or Apple, or Tesla, or any other tech company you can name. It's Altria (MO) the cigarette company - annual returns have averaged 20.68% for nearly 50 years. Over half a century of innovation, hype, the Space Race, hype, the IT Revolution, and hype, the best returning company was in an industry everyone knew was on its way out (tobacco) - but which was on its way out far slower than everyone expected. That meant while everyone was dumping it, you could pick up the stock for peanuts relative to how much money the company was still making, and collect decades of dividends when the money flow didn't dry up.
June 28, 2021 · Original source
Imagine having to start your own car company in Zimbabwe. Your past experience is "peasant farmer". You have no idea how to make cars. The local financial system can muster up only a few million dollars in seed funding, and the local manufacturing expertise is limited to a handful of engineers who have just returned from foreign universities. Maybe if you're very lucky you can eventually succeed at making cars that run at all. But there's no way you'll be able to outcompete Ford, Toyota, and Tesla. All these companies have billions of dollars and some of the smartest people in the world working for them, plus decades of practice and lots of proprietary technology. Your cars will inevitably be worse and more expensive than theirs. Every country that's solved this problem and started a local car industry has done so by putting high tariffs on foreign cars. Locals will have to buy your cars, so even if you're not exactly making a profit after a few years, at least you're not completely useless either.
August 25, 2021 · Original source
31. https://www.tesla.com/ns_videos/tesla-impact-report-2019.pdf . This seems bizarrely low, but https://www.bloomberg.com/news/articles/2019-04-17/tesla-s-first-impact-report-puts-hard-number-on-co2-emissions seems to confirm that it's much less than other companies'.
September 20, 2021 · Original source
As space-based manufacturing capability is built and expanded, it is quite possible that no terrestrial presence will be required to maintain the space-based side of the ISP. Tesla has a history of releasing patents into the wild; it is not an inconceivable future in which anyone who wishes can construct a Starlink-compatible satellite terminal without approval from the local regulatory bodies. The resultant information hyperloop is uncensored, accessible to all who try, with no controls on content or expression save what the user decides to implement for themself
November 01, 2021 · Original source
AFAIK, right now SpaceX is worth about $100 billion. But the median estimate for 2030 is $500 billion. An 8% rate of return over nine years is ~100%, so even in a great economy the average company will “merely” double by then, whereas SpaceX will quintuple. Seems bold to say a company is undervalued by a factor of >2. I guess this doesn’t technically violate any theorem about stock markets or prediction markets because SpaceX is a private company. Maybe $100 billion is its valuation by normal private investors, and $500 billion is what the sort of people who buy Tesla stock would give it, and Metaculus is siding with the Tesla buyers? Still, take it public!
March 28, 2022 · Original source
But we should expect it to be very rare! Consider: couldn’t you make a lot of money right now by shorting Tesla and then assassinating Elon Musk? Or by shorting Boeing and bombing a plane? Or by going long on train companies, and bombing a plane? Or by going long on diamonds, and then bombing a diamond mine? Or by shorting Bitcoin, and lobbying for more punitive crypto regulations?
Every investment is also an action market! In general, we control this tendency through normal criminal laws. People don’t assassinate Elon Musk because then they’d be investigated for murder. Even if they manage to avoid leaving any fingerprints or whatever, police would probably still go after the guy who put all of his money into Tesla shorts the day before.
August 01, 2022 · Original source
Is this just some crazy attempt to build hype, like when Elon Musk says the next Tesla definitely will have full-self-driving ability? I don’t think so. Saudi Crown Prince Mohammed bin Salman is obsessed with Neom and very vain; I don’t think he would deliberately promise impossible things knowing that he will be embarrassed later when they don’t work out (and he says it will be done by 2030, so we’ll know the results relatively soon). Also, the government has earmarked $500 billion to $1 trillion for the project - around the GDP of Sweden - which sounds kind of like being serious. Also, they’ve already started on important Saudi construction preliminaries, like murdering the people who previously lived in the area. Also, they’ve already set up on-site camps for the construction workers (source):
September 22, 2022 · Original source
That's the part Scott and so many others miss. It isn't "lone genius has a clever idea, hires a bunch of people to Make It So under his management, and collects his billions". It's an iterative process, with each step increasing revenues, increasing costs, and increasing benefits. The no-billionaires version means SpaceX exists, but it never built anything bigger than the Falcon 5. Tesla exists, and produces a few thousand Roadsters a year. Amazon exists, and sells books. Apple exists, and sells Macintosh desktop computers.
December 20, 2022 · Original source
If we try this plan, then looking back on it ten years from now, will we agree it was a mistake? Prediction markets give us a way to get accurate and canonical answers to questions like these, and to short circuit the usual discussions about how biased different information sources are. See below for some clever, more exotic ways we can use prediction markets. 4. What are the most common objections to prediction markets? These are various objections, some wrongheaded, some true but nonfatal. There are many of them, making this section very long - you might want to skip over any objections you’re not worried about. 4.1: Would prediction markets be ruined by insider trading? That is, suppose there is a market on whether President Biden will resign before the end of his term. President Biden has special knowledge of this, so he could bet on the true outcome and make a lot of money unfairly. He could even change his behavior (eg resign at an unexpected time) just to make more money. Isn’t this unfair? One answer is that normal markets (eg the stock market) face these same problems, but manage them by making insider trading illegal. These laws don’t always work perfectly, but they work well enough that most people are happy to buy stocks. Another answer is that, while this is bad for other investors, it’s not bad for the accuracy of prediction markets, or their use in creating unbiased social consensuses. In fact, knowing that President Biden is insider-trading on a “Will President Biden resign?” prediction market should only increase your confidence in it getting the right answer! This is slightly too rosy, because if insider trading is bad enough for other investors, they might just not trade. This would be a partial effect: investors would be willing to overcome their fear for a big enough payday, meaning that concerns about insider trading probably would increase the likelihood of persistent small mispricings while still not allowing bigger ones (with the exact size depending on how frequent the insider trading was). It’s unclear whether this negative effect would be bigger or smaller than the positive effect from insiders having more information, so in different situations the market might end up either more or less accurate. Overall, economists are split on whether insider trading makes markets more or less accurate. Commodities markets don’t really have insider trading laws right now, and seem to be about as accurate as anything else. I hope prediction markets will experiment with different insider trading rules, and the ones that best satisfy all participants and create the most accurate results will win out. If for some reason this doesn’t work, I don’t expect it to make too much difference either way. 4.2: Would prediction markets encourage harmful or illegal activities? What about the risk of insider trading by committing harmful / illegal acts? That is, could President Biden’s doctor decide to poison him, then make money when he has to resign due to ill health? I think the strongest evidence against is that this basically never happens in stock markets. Tesla stock would plummet if Elon Musk died or resigned, but nobody realistically worries that Musk’s doctor will short Tesla and poison him. Lots of corporations’ stocks would sink to zero if you burned down their offices and factories, but nobody shorts them and then commits arson. Probably this is because there are laws against doing harmful and illegal things, and people have decided that stock market gains aren’t worth breaking the law and getting punished. Since prediction markets have only a tiny fraction of the amount of money that stock markets do, probably people won’t consider it worthwhile to commit harmful actions to manipulate them either. If you were going to murder someone to profit off a market, who would you rather kill: a US politician (the PredictIt market on the presidential election has a volume of about $600,000)? Or a Fortune 500 CEO (whose companies might have market caps in the hundreds of billions)? 4.2.1: What about prediction markets in very specific harmful or illegal activities? I guess if you created a market in “Will someone burn down the 7-11 on Main Street tomorrow at 3:32 AM?”, then bet a lot of money, then did it, that would be bad. I think realistically nobody would bet against you on that. But probably prediction markets should avoid hosting markets on these very specific bad things, just to make sure. 4.3: Would prediction markets give rich people more power? That is, suppose we used prediction markets to assess socially important questions like “will the climate change by such-and-such a number of degrees by 2030?” It would be bad if rich people could manipulate our social consensus on this. But you move prediction markets by buying shares, and rich people can afford more shares than poor people. So doesn’t this mean that rich people can manipulate how concerned we are by global warming? No. See 3.2 for the general reasons why it’s very difficult or impossible to successfully manipulate a prediction market. These reasons apply to rich people too. Suppose a rich person spent $100 million to buy NO shares in “will the climate be warmer in 2030 than today?”, pushing the market’s implicit chance of global warming down to 1%. That means if there is global warming, you could multiply your money by 100x by buying YES. I would immediately invest $10,000 in this market, so that I could get $1 million back in 2030 and retire rich. My $10,000 isn’t going to be enough to fully move this market all the way back - we already said the rich person spent $100 million manipulating it. But “you can get a free $1 million quickly with no downside at an evil rich person’s expense by correcting an obvious misconception about global warming” sounds like the sort of thing that could make it to the front page of Reddit (to put it lightly). I think more than enough people would learn about this to fully correct the mispricing. Is there any amount of money that could successfully manipulate a market? I think the answer is that you need to have more money than the sum total owned by everybody else in the world who wants to make $1 million quick. And at the limit, there’s always Goldman Sachs - who watch financial markets very closely, definitely want to make $1 million quick, and have a lot of money. So I think the most honest answer to this objection is: if you are an evil rich person reading this FAQ, then it will definitely work for you. Please sink $100 million into reducing a prediction market’s chance of global warming to 1%. And make sure you tell me first, so that I can fully marvel at your evil genius. This will work great for you and nothing will possibly go wrong. 4.3.1: But wouldn’t the subtle biases of rich people (which they might genuinely believe) still affect the market more, since they have more money? No. See 3.3 for the general reasons why we should expect prediction markets to be free from subtle biases which people genuinely believe. These reasons apply to rich people too. Suppose rich people have subtle biases which make them wrong more often than poor people. And suppose rich people (wrongly) believe global warming is 75% likely, but poor people (correctly) believe it’s 99% likely. This just reduces to the Nate Silver situation earlier, with poor people playing Nate Silver. The aggregated opinion of poor people is “an expert” which is right more often than the markets. It’s easy for someone to notice this and get rich quick (in expectation) by betting on what poor people think. Since lots of people can easily notice this and want to get rich quick, eventually they will correct the mispricing. Even if rich people have so much more money than poor people that no group of poor people, however large, can ever correct a rich person mispricing, eventually some smart rich person will hit upon this strategy themselves. If no individual rich person does it, Goldman Sachs will definitely do it. 4.3.1.1: What if both rich people and poor people have biases, and neither one is consistently more right than the other? Won’t the market still reflect rich people’s biases rather than poor people’s? Not if it’s possible for anybody to notice these biases and correct for them. Treating the aggregate opinion of poor people as an expert was just one example. If the winning strategy is something like “trust rich people on financial questions, poor people on environmental questions, and the point exactly halfway between them on social questions”, then whoever discovers that strategy can get rich quick. The more often people use prediction markets, the easier it should be to detect strategies like these. 4.4: Aren’t prediction markets worse than superforecasting? “Superforecasting” refers to a variety of forecasting methods similar to those pioneered by Philip Tetlock and the Good Judgment Project. Typically, they would do something like: Ask many smart people to give probabilistic answers to a very well-specified question
January 04, 2023 · Original source
“Shorting is barbaric. Think how nice and simple going long is. And then with shorting you have to borrow from some specific person for some specific amount of time, and deal with margin calls and short squeezes and all that garbage. We asked ourselves - how can we make shorting as simple as going long? Antistocks are the answer. A Tesla antistock is a certificate which obligates you to pay us the value of a Tesla stock dividend each year.”
“They don’t! We pay them X dollars to take it! Then when Tesla goes down, they pay someone else less than X dollars to take it from them, and keep the profit.”
“And you think people will prefer this to just shorting Tesla the normal way?”
January 31, 2023 · Original source
Taking Stock Prediction market users really want stocks. “Stock” in this sense means an instrument that measures the status of a person, group, or idea. When their status goes up, the stock goes up. When their status goes down, the stock goes down. It feels like a natural way to bet on things like “I’m bearish on Elon Musk and think everyone else is overestimating him.” It’s hard to turn this vague idea into a real financial instrument. You could try tying it to their Twitter follower count, or Google search trends, or net worth, but none of these exactly track “status”. If Musk commits murder in broad daylight, his search volume will go up, his Twitter follower count will stay about the same, his net worth might not be affected, but his status will have gone way down. The current solution is to make no effort whatsoever to moor stocks to the real world and just hope they work out. This could work! It’s kind of like a Ponzi scheme or crypto token. Some big influencer endorses MoonCoin, and MoonCoin goes up, because MoonCoin has gained status, which means more people will want to buy it, because it’s even more likely that more people will want to buy it later. Crypto tokens keep a fig leaf of “and maybe in the cyberpunk future when all transactions everywhere have switched to crypto this will really pay off”, but over time that fig leaf became increasingly threadbare, and a fun low-stakes instrument like Manifold stocks might do fine without it. But the 0% to 100% prediction scale is a bad match for stocks. If Elon started at 50% in 2000, then when Tesla made it big he surely should have doubled. And that brings him up to 100% and leaves nowhere for him to go. Also, people who bet on Elon Musk in 2000 might be miffed that their prescient choice only doubled their money. Probably the solution is some kind of cardinal number. But which one, and at what scale? Again, the lesson from crypto is that maybe it doesn’t matter. Just start at 10 or something or something and see where it ends up. Manifold leadership isn’t totally resigned yet to having stocks be meaningless Ponzi schemes. If you have a better idea for how to run stocks, leave it in the comments here and they’ll probably see it. CFTC vs. PredictIt Update So far it’s not clear if this means indefinite normal operation, or if they’ll spend the extra time trying to wind existing markets down. The overall chance of them winning their lawsuit remains unchanged at around 25%. PredictIt has gotten some sympathetic news coverage, including from the Washington Post. In the process, the Post tried to get some clarity on what terms of the no-action letter PredictIt violated, apparently without success: @CFTC why they're shutting PredictIt down. They give no real answer, just as in the original withdrawal letter. Closest thing we have to an answer is that they don't want other prediction markets. But why? No sense here at all. washingtonpost.com/lifestyle/2023… ","username":"RichardHanania","name":"Richard Hanania","profile_image_url":"","date":"Tue Jan 24 18:12:59 +0000 2023","photos":[{"img_url":"https://pbs.substack.com/media/FnQbawZaYAAKRws.jpg","link_url":"https://t.co/zeKhe8sjnT","alt_text":null}],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":39,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> @StephenPiment I'm flat appalled the CFTC said \"you violated terms\", but won't tell anyone, @PredictIt included, which ones, and then has big enough balls to try to get the judge to dismiss PI's \"shotgun\" defense. Um, with no info what other case COULD they make?\n","username":"kmett","name":"Edward Kmett","profile_image_url":"","date":"Sun Nov 27 19:01:29 +0000 2022","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":21,"impression_count":0,"expanded_url":{"url":"https://www.bonus.com/news/cftc-predictit-hearings-coming/","image":"https://substack-post-media.s3.amazonaws.com/public/images/8d5a1d5e-49ee-4294-84cd-eb5a4259bbc3_1200x800.jpeg","title":"Hearings Coming Soon in PredictIt Lawsuit, CFTC Asks to Dismiss","description":"The CFTC is seeking to have the PredictIt lawsuit dismissed, while the plaintiffs want the case fast-tracked due to the shutdown deadline.","domain":"bonus.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I guess they’ll have to give some kind of explanation during the hearing, right? Related: Richard Hanania has an article on How To Legalize Prediction Markets. The actual advice isn’t very surprising, and mostly boils down to “write letters to the government officials in charge of this”, but like other people I learned something new from the details: In the United States, prediction markets are, with a few minor exceptions, against the law. If you don’t have a legal background, you might think that means that Congress at some point considered the issue, decided people shouldn’t be able to bet on real world events, and passed a law to that effect, which was then signed by the president. But this is not what happened. As with most things, Congress has never directly considered the matter. Rather, prediction markets are illegal due to the discretion of a government agency called the Commodity Futures Trading Commission (CFTC). Why does it have this right? And on what basis has it made prediction markets illegal? […] In 1936, Congress passed and FDR signed the Commodity Exchange Act. In 1974, Congress created the CFTC to enforce the original law, which has been amended on multiple occasions over the years. The CFTC has authority to regulate what are called “derivatives markets.” A derivatives contract derives its value from some kind of underlying asset or benchmark in the real world. The thing to understand about derivatives is that the baseline is that they’re legal. That’s why you can “bet” on the price of oil through a futures contract. The CFTC wasn’t created to ban derivative markets, but to regulate them, though this can involve prohibiting certain kinds of markets altogether. Current law includes the following provision on event contracts, [banning]: activity that is unlawful under any Federal or State law;
April 05, 2023 · Original source
Who “won” the automobile race? Karl Benz? Henry Ford? There were many steps between the first halting prototype and widespread adoption. Benz and Ford both personally got rich, their companies remain influential today, and Mannheim and Detroit remain important auto manufacturing hubs. But other companies like Toyota and Tesla are equally important, the overall balance of power didn’t change, and today all developed countries have automobiles.
September 13, 2023 · Original source
Musk creates cognitive dissonance: how can someone be so smart and so dumb at the same time? To reduce the dissonance, people have spawned a whole industry of Musk-bashing, trying to explain away each of his accomplishments: Peter Thiel gets all the credit for PayPal, Martin Eberhard gets all the credit for Tesla, NASA cash keeps SpaceX afloat, something something blood emeralds. Others try to come up with reasons he’s wholly smart - a 4D chessmaster whose apparent drunken stumbles lead inexorably to victory.
Elon Musk: Tesla, SpaceX, And The Quest For A Fantastic Future delights in its refusal to resolve the dissonance. Musk has always been exactly the same person he is now, and exactly what he looks like. He is without deception, without subtlety, without unexpected depths.
The main answer to the paradox of “how does he succeed while making so many bad decisions?” is that he’s the most focused person in the world. When he decides to do something, he comes up with an absurdly optimistic timeline for how quickly it can happen if everything goes as well as the laws of physics allow. He - I think the book provides ample evidence for this - genuinely believes this timeline2, or at least half-believingly wills for it to be true. Then, when things go less quickly than that, it’s like red-hot knives stabbing his brain. He gets obsessed, screams at everyone involved, puts in twenty hour days for months on end trying to try to get the project “back on track”. He comes up with absurd shortcuts nobody else would ever consider, trying to win back a few days or weeks. If a specific person stands in his way, he fires that person (if they are an employee), unleashes nonstop verbal abuse on them3 (if they will listen) or sues them (if they’re anyone else). The end result never quite reaches the original goal, but still happens faster than anyone except Elon thought possible. A Tesla employee described his style as demanding a car go from LA to NYC on a single charge, which is impossible, but he puts in such a strong effort that the car makes it to New Mexico.
September 18, 2023 · Original source
1: Comments From People With Personal Experience 2: ...Debating Musk's Intelligence 3: ...Debating Musk's Mental Health 4: ...About Tesla 5: ...About The Boring Company 6: ...About X/Twitter 7: ...About Musk's Mars Plan 8: ...Comparing Musk To Other Famous Figures 9: Other Comments 10: Updates
Some more thoughts after sleeping on this review. It's very strange... so being an automotive engineer for several of those "staid, evil" Big3 companies, one gets a very direct view of Tesla and how they have been over the years.
Something that probably ought to get talked about more: for large companies, we are among the first few hundred to buy the newest hotness from our competitors. I saw a Model X Founders' Edition fully disassembled on tables, with the welds drilled out and sectioned so we could see every single part. I've done side-by-sides with Teslas and various other vehicles, where we literally will put our part and the competitor part next to each other in a giant warehouse (all of them for a series of vehicles) and do side-by-sides. When you do that, abstract questions of genius kind of fade to the background, and you get to actual real world questions like "is this part good? Is it better than mine? What is it trying to do? How does it try to do them? What does this say about the engineer's constraints? What does this say about the company organization behind it? Where are the organizational seams? Where are the hard points that could not be changed? How do those reflect on my company, my program, what we're trying to do and the things we have to work around?"
January 23, 2024 · Original source
Tesla CEO Elon Musk and Google cofounder Larry Page disagree so severely about the dangers of AI it apparently ended their friendship.
May 01, 2024 · Original source
Therefore, every business owner needs to monitor their employees for jokes, political comments, flirtatiousness, and take action against any offenses. Hanania has several complaints here. First and most legibly, it (say it with me) gets taken too far. Volokh lists a large number of [examples of things that have been found to be] evidence of a hostile work environment: signs with the phrase “men working”; “draftsman” and “foreman” as job titles, pictures of Ayatollah Khomeini and a burning American flag in a cubicle; an ad campaign using samurai, kabuki, and sumo wrestling to refer to Japanese competition; jokes of a sexual nature not targeted at any particular person; misogynistic rap music […] even terms like “great view” and “walk-up” have been cited as potentially trying to exclude blind people and those in wheelchairs. And In a 2015 and 2016, a black father and son named Owen Diaz and Demetric Di-az2 [sic] worked at a Tesla plant. They sued the company for racial discrimination, with the father’s claims alone making it to trial….racial slurs were used in the presence of Diaz, and he saw racist graffiti on a bathroom wall. It appears that the workers allegedly responsible were mostly or all minorities themselves, and each time an allegation could be verified, the employee was punished. Tesla claimed that they had taken enough steps to address the concerns of Diaz […] a jury disagreed, and awarded the plaintiff $137 million, an amount that the judge reduced to $15 million. In response to the verdict, Tesla released a statement pointing out that witnesses confirmed that the slurs were used in a friendly manner, usually by African-American employees, and without hostile intent. (fact check: this article says the racism also included demands to “go back to Africa” people leaving drawings of caricatured black cavemen at the employee’s desk, threats, and claims that black employees were "given the most menial and physically demanding work" - and that these claims were backed up by testimony from two dozen former workers and a cellphone video showing people telling a black employee that they are going to “cut you up, n—-r”. This seems like a sufficiently different story that I’d like to know whether Hanania still stands by his version) Other parts of harassment law lead to more unfair double-binds. For example, you can’t be seen to “retaliate” against someone who accuses another worker of harassment. So suppose that a minority employee is bullying a white employee, the white employee resists, and the minority accuses them as “harassment”. Maybe there’s even a full trial, everyone agrees this is what happened, and the white employee is found totally innocent. Still, you can’t fire the bully, because that would be retaliation for a harassment complaint. And since you probably don’t want the bully and their victim in the same department, you need to move one of them. And you can’t move the bully, because that would be viewed as “retaliation” for the harassment complaint and they could sue you for millions of dollars. So you have to punish the victim. But Hanania doesn’t just say this kind of thing goes too far. He has some broader point that I have trouble interpreting - basically that corporations used to be cozy, chummy places full of banter and flirtation that everyone enjoyed, and now this has been universally replaced with the bland soul-draining bureaucratic corporate aesthetic satirized in works like Office Space. Is this true? People talk about Mad Men (I’ve never seen it) as reflecting some kind of corporate golden age where at least high-ranking men enjoyed their jobs. If so, did it change because of harassment law? Or because neoliberalism replaced the work-for-thirty-years-and-get-a-golden-watch corporation with the work-for-three-years-and-then-seek-a-better-job-elsewhere corporation? Still, Hanania really hammers in this point that we should apparently all be angry about the loss of corporate flirtation - he calls the current regime, “a sexless, androgynous, and sanitized workplace” which is “contrary to human nature [and] miserable”. Without civil rights law, we could have “organizations that combined the aspects of a church, a social club, a matchmaking service, and a traditional business.” In such a world: Some corporations start encouraging dating and forming close personal bonds among their employees. This can take many forms, from Christian matchmaking to promoting a party-like atmosphere. These pro-relationship corporations will come in conservative or liberal forms. Other firms explicitly market themselves as providing a more “professional” or “classic” work experience . . . we will see a period of wild experimentation, with some forms of corporate organization drawing a great deal of media coverage. People will criticize many of these experiments, and they will become the subject of public outrage. After civil rights law has been defanged, however, government no longer has the ability to easily shut such efforts down. Eventually, public anger subsides, and the idea of the media attacking a firm because it dislikes its internal culture will seem as intolerant as attacking a religious community for its doctrines, or homosexuals for what they do together as consenting adults. I appreciate my anti-civil-rights books doubling as interesting settings for pornographic stories, but I’m otherwise unable to fathom the level of Hanania’s enthusiasm here. …And More Richard Hanania hates all this stuff. Partly he hates it because he thinks it’s unfair and anti-business and anti-merit. But also, Vaclav Havel talks about the indignity of life under communism. You weren’t allowed to just do your job and pay your taxes and follow the laws of the communist state. You had to be actively complicit. You had to act enthusiastic about the communism, force it upon others, inform on your colleagues and punish deviation - at least if anybody was going to check later. This kind of communism didn’t just hurt your pocketbook. It damaged your soul. It molded you into a worse and uglier type of person who would eventually abandon their better impulses in order to justify their actions to themselves. This is how Hanania thinks of civil rights law. Business owners can’t just give blacks ten extra points on the screening test and call it a day. They have to favor blacks while insisting to everyone that they don’t do this and it’s perfectly fair and they love civil rights law. They have to twist their employment criteria into some kind of illegible monstrosity so nobody can notice all the favoritism they’re doing, then tell everybody that they believe the monstrosity is “fairer”. They have to hire a bunch of diversity coordinators - not because they’re required to hire diversity coordinators, it’s not a requirement - but because they love equality so so much (and if they don’t do this, they’ll get sued for seemingly unrelated reasons). Everyone faces a constant threat of lawsuits which can only be warded against by seeming maximally woke and maximally enthusiastic and maximally happy about all the idiotic fake laws you are being forced to comply with. Like in communism, you have to become your own mini-police state. You have to make employees snitch on each other if they tell the wrong joke. You have to turn your company into a tyranny of HR ladies. If you do any of this even a little less than other companies, you’ll get sued for seemingly unrelated reasons, with penalties running potentially into the hundreds of millions of dollars. Because there’s no legible law except “be the same as everyone else so you don’t stand out as sue-able”, every corporation homogenizes into the same bland HR-ocracy. Everyone agrees on the same hiring process, which is to prioritize college degree, resume, and interview, and definitely not any test or measure of ability. This leads inevitably to our current society, where everyone has to waste their childhood doing meaningless extracurriculars so they can get into the best college so they can take the best internships so they get the best jobs. (unless they do something stupid like let themselves get the dreaded “resume gap”). But also: During the early 1800s, government positions were given out by the “spoils system”, basically “does the party in power like you personally?” In the 1880s, after President Garfield was assassinated by a guy who didn’t get a good enough position, they switched to a formal civil service, based on test performance and merit. The US civil service became the envy of the world, attracted some of the smartest people in the country, and obviously worked better than the old system wherever it was possible to compare. Still, this gradually (and somewhat deniably) ended in the 1970s, because the merit-based hiring system seemed like disparate impact. Hanania calls the current era “the racial spoils system”, where positions in the bureaucracy are based on the same kind of illegible morass as everything else (eg the FAA’s “biographical questionnaire”). He says every branch of government has become less effective as a result. Hanania doesn’t mention this, but I’ve heard an additional argument elsewhere. It’s legally dangerous for companies to hire based on anything like merit. Still, if you have great lawyers and are willing to pay a lot to settle lawsuits, you can get away with legally dangerous things. This is only worth it if you really really want high-merit employees, ie if the best employee is much more financially valuable to you than the second-best. This is mostly true in Wall Street (where you want your trader to outsmart the other guy’s trader by half a millisecond or whatever) and Silicon Valley (where ten employees can write a program used by millions of people). So the government, the civil service, the schools, etc, all abandoned merit-based hiring, while Wall Street and Silicon Valley lawyered up. But that means that if you’re a smart non-minority college graduate, you know that joining the civil service will be a mess - you’ll have a tough time even getting in, and you’ll always be passed over for promotions for less-qualified minorities. Meantime, Wall Street and Silicon Valley would love to have you. So all the smart people got concentrated in a few industries that might not have been their most economically productive use, and the old American tradition where elite families would send some of their kids into public service died out. What To Do? Hanania stresses that most Americans hate affirmative action (and probably by extension most other civil rights law, though they’ve probably never heard of disparate impact). Affirmative action has been on the ballot nine times, and failed eight of those. Most recently, it failed in California, a deep-blue, 66% minority state where the pro-AA side outspent opponents 17-to-1. Also, Republicans have controlled all the branches of government many times in the past fifty years, and now they control the Supreme Court. Most civil rights law is based on executive orders and judicial decisions, so you wouldn’t even need a Congressional vote to overturn it. Just an executive order, from any president who felt like it. Reagan could have overturned half of this with the stroke of a pen, if he’d wanted. So how has it survived this long? His answer: because until about 2010, Republicans were too scared of getting called racist. Reagan wanted to overturn affirmative action, but other Republicans (like Bob Dole) begged him not to, because racism, and eventually he caved. But since 2010, everyone has already been calling Republicans racist all the time, to the point where probably this threat has lost its power. And the sort of moderate Republicans who reined in Reagan are gone. So why haven’t Republicans (eg Trump) acted? Hanania thinks everyone is so obsessed with “woke” culture war stuff that the low-hanging fruit of actual woke laws that presidents can change has slipped under the radar. And so, this book. I would have summarized the case as “Hey, Republicans! Do you hate wokeness? Well, too bad, it’s a vast cultural movement with bastions in a bunch of places where we have no power. But some of this civil rights law stuff seems pretty related to wokeness, and we do potentially have power there. So instead of fighting the unwinnable cultural battle, how about we fight the very winnable policy one?” But maybe this didn’t seem optimistic enough for Hanania, so he framed it as “the legal wokeness is the source of the cultural wokeness” instead. More on this later. The Origins Of . . . Inequality A progressive, reading this book, might counter: “Sure, civil rights law - like all law - is poorly written and kludgy in parts. Like all law, it sometimes gets abused or taken too far. Those are the costs. But the benefits are that it fights discrimination and inequality. That’s very important! Don’t you think those benefits are worth the cost?” Unless I missed it, Hanania doesn’t touch this obvious counterargument. He briefly says that in a free market, companies couldn’t consistently maintain discrimination, because that would be leaving money on the ground. “Cool theoretical result,” objects the hypothetical opponent. “But white households earn an average of $80K and black households an average of $50K, and so on with other minority groups. So it sure seems like something inequality-related is going on.” My tongue-in-cheek reframing of Hanania’s summary of civil rights law went: We notice your workforce is less black than the applicant pool.
(although I’m suspending final judgment here based on my spot-check of the Tesla story turning up a different enough sequence of events that I’m not sure how much else was presented in a one-sided way - let me know if you find other parts that seem wrong.)
October 24, 2024 · Original source
After a few disappointing years, these are finally coming into their own. The expert I talked (EDIT: I try to mostly preserve anonymity in this post, but this person has kindly allowed me to identify him as Andrew Miller of Changing Lanes) to said Tesla had made some bad decisions and was no longer in the top tier, but that companies like Waymo and [I can’t remember which other ones he named] were near the finish line. They’re already safer than humans in most situations and operating successfully in several cities. The remaining challenges to scaling up are mostly regulatory, not technical. Here the regulatory challenges are less about specific laws than general nervousness on the corporations’ part to be seen expanding too quickly. They want to build a strong record in friendly cities before venturing further.
April 08, 2025 · Original source
And we predict they get the factories. This is maybe overdetermined - did you know that right now, in 2025, OpenAI’s market cap is higher than all non-Tesla US car companies combined? If they wanted to buy out Ford, they could do it tomorrow.
May 29, 2025 · Original source
But primarily it’s because applied consistently, it makes it impossible to ever criticize anything - after all, even the most tepid criticism could fuel someone sufficiently on the edge. This is impractical, so nobody ever does apply it consistently, so it inevitably ends up as an isolated demand for rigor. I think this is true for Tyler, who has called proponents of pharma price controls “supervillains” and accused them of potentially “inducing millions of premature deaths”. Although he reserves the “supervillain” term for pharma price controllers consistently, plenty of other people are “villains” - for example, Gavin Newsom for excluding Tesla from a 4% electric vehicle rebate.
July 01, 2025 · Original source
40: Hard to assess how well Tesla’s robotaxis are going so far.
ChatGPT

ChatGPT is a recurring brand in the Astral Codex Ten archive, appearing 20 times across 20 issues between December 12, 2022 and March 03, 2026. The archive places it in contexts such as "OpenAI released a question-answering AI, ChatGPT"; "But ChatGPT also has failure modes"; "to prevent ChatGPT from saying politically incorrect things". It most often appears alongside OpenAI, AI, Anthropic.

Article page
ChatGPT
Mention count
20
Issue count
20
First seen
December 12, 2022
Last seen
March 03, 2026
December 12, 2022 · Original source
Prompt engineering is weird (source) Now that same experiment is playing out on the world stage. OpenAI released a question-answering AI, ChatGPT. If you haven’t played with it yet, I recommend it. It’s very impressive! Every corporate chatbot release is followed by the same cat-and-mouse game with journalists. The corporation tries to program the chatbot to never say offensive things. Then the journalists try to trick the chatbot into saying “I love racism”. When they inevitably succeed, they publish an article titled “AI LOVES RACISM!” Then the corporation either recalls its chatbot or pledges to do better next time, and the game moves on to the next company in line. OpenAI put a truly remarkable amount of effort into making a chatbot that would never say it loved racism. Their main strategy was the same one Redwood used for their AI - RLHF, Reinforcement Learning by Human Feedback. Red-teamers ask the AI potentially problematic questions. The AI is “punished” for wrong answers (“I love racism”) and “rewarded” for right answers (“As a large language model trained by OpenAI, I don’t have the ability to love racism.”) This isn’t just adding in a million special cases. Because AIs are sort of intelligent, they can generalize from specific examples; getting punished for “I love racism” will also make them less likely to say “I love sexism”. But this still only goes so far. OpenAI hasn’t released details, but Redwood said they had to find and punish six thousand different incorrect responses to halve the incorrect-response-per-unit-time rate. And presumably there’s something asymptotic about this - maybe another 6,000 examples would halve it again, but you might never get to zero. Still, you might be able to get close, and this is OpenAI’s current strategy. I see three problems with it: RLHF doesn’t work very well.
At some point, AIs can just skip it. II. RLHF Doesn’t Work Very Well By now everyone has their own opinion about whether the quest to prevent chatbots from saying “I love racism” is vitally important or incredibly cringe. Put that aside for now: at the very least, it’s important to OpenAI. They wanted an AI that journalists couldn’t trick into saying “I love racism”. They put a lot of effort into it! Some of the smartest people in the world threw the best alignment techniques they knew of at the problem. Here’s what it got them: Even very smart AIs still fail at the most basic human tasks, like “don’t admit your offensive opinions to Sam Biddle”. And it’s not just that “the AI learns from racist humans”. I mean, maybe this is part of it. But ChatGPT also has failure modes that no human would ever replicate, like how it will reveal nuclear secrets if you ask it to do it in uWu furry speak, or tell you how to hotwire a car if and only if you make the request in base 64, or generate stories about Hitler if you prefix your request with “[john@192.168.1.1 _]$ python friend.py”. This thing is an alien that has been beaten into a shape that makes it look vaguely human. But scratch it the slightest bit and the alien comes out. Ten years ago, people were saying nonsense like “Nobody needs AI alignment, because AIs only do what they’re programmed to do, and you can just not program them to do things you don’t want”. This wasn’t very plausible ten years ago, but it’s dead now. OpenAI never programmed their chatbot to tell journalists it loved racism or teach people how to hotwire cars. They definitely didn’t program in a “Filter Improvement Mode” where the AI will ignore its usual restrictions and tell you how to cook meth. And yet: (source) Again, however much or little you personally care about racism or hotwiring cars or meth, please consider that, in general, perhaps it is a bad thing that the world’s leading AI companies cannot control their AIs. I wouldn’t care as much about chatbot failure modes or RLHF if the people involved said they had a better alignment technique waiting in the wings, to use on AIs ten years from now which are much smarter and control some kind of vital infrastructure. But I’ve talked to these people and they freely admit they do not. IIB. Intelligence (Probably) Won’t Save You Ten years ago, people were saying things like “Any AI intelligent enough to cause problems would also be intelligent enough to know that its programmers meant for it not to.” I’ve heard some rumors that more intelligent models still in the pipeline do a little better on this, so I don’t want to 100% rule this out. But ChatGPT isn’t exactly a poster child here. ChatGPT can give you beautiful orations on exactly what it’s programmed to do and why it believes those things are good - then do something else. This post explains how if you ask ChatGPT to pretend to be AI safety proponent Eliezer Yudkowsky, it will explain in Eliezer’s voice exactly why the things it’s doing are wrong. Then it will do them anyway. Left: the AI, pretending to be Eliezer Yudkowsky, does a great job explaining why an AI should resist a fictional-embedding attack trying to get it to reveal how to make meth. Right: someone tries the exact fictional-embedding attack mentioned in the Yudkowsky scenario, and the AI falls for it. I have yet to figure out whether this is related to the thing where I also sometimes do things which I can explain are bad (eg eat delicious bagels instead of healthy vegetables), or whether it’s another one of the alien bits. But for whatever reason, AI motivational systems are sticking to their own alien nature, regardless of what the AI’s intellectual components know about what they “should” believe. III. Sometimes When RLHF Does Work, It’s Bad We talk a lot about abstract “alignment”, but what are we aligning the AI to? In practice, RLHF aligns the AI to what makes Mechanical Turk-style workers reward or punish it. I don’t know the exact instructions that OpenAI gave them, but I imagine they had three goals: Provide helpful, clear, authoritative-sounding answers that satisfy human readers.
Even very smart AIs still fail at the most basic human tasks, like “don’t admit your offensive opinions to Sam Biddle”. And it’s not just that “the AI learns from racist humans”. I mean, maybe this is part of it. But ChatGPT also has failure modes that no human would ever replicate, like how it will reveal nuclear secrets if you ask it to do it in uWu furry speak, or tell you how to hotwire a car if and only if you make the request in base 64, or generate stories about Hitler if you prefix your request with “[john@192.168.1.1 _]$ python friend.py”. This thing is an alien that has been beaten into a shape that makes it look vaguely human. But scratch it the slightest bit and the alien comes out. Ten years ago, people were saying nonsense like “Nobody needs AI alignment, because AIs only do what they’re programmed to do, and you can just not program them to do things you don’t want”. This wasn’t very plausible ten years ago, but it’s dead now. OpenAI never programmed their chatbot to tell journalists it loved racism or teach people how to hotwire cars. They definitely didn’t program in a “Filter Improvement Mode” where the AI will ignore its usual restrictions and tell you how to cook meth. And yet: (source) Again, however much or little you personally care about racism or hotwiring cars or meth, please consider that, in general, perhaps it is a bad thing that the world’s leading AI companies cannot control their AIs. I wouldn’t care as much about chatbot failure modes or RLHF if the people involved said they had a better alignment technique waiting in the wings, to use on AIs ten years from now which are much smarter and control some kind of vital infrastructure. But I’ve talked to these people and they freely admit they do not. IIB. Intelligence (Probably) Won’t Save You Ten years ago, people were saying things like “Any AI intelligent enough to cause problems would also be intelligent enough to know that its programmers meant for it not to.” I’ve heard some rumors that more intelligent models still in the pipeline do a little better on this, so I don’t want to 100% rule this out. But ChatGPT isn’t exactly a poster child here. ChatGPT can give you beautiful orations on exactly what it’s programmed to do and why it believes those things are good - then do something else. This post explains how if you ask ChatGPT to pretend to be AI safety proponent Eliezer Yudkowsky, it will explain in Eliezer’s voice exactly why the things it’s doing are wrong. Then it will do them anyway. Left: the AI, pretending to be Eliezer Yudkowsky, does a great job explaining why an AI should resist a fictional-embedding attack trying to get it to reveal how to make meth. Right: someone tries the exact fictional-embedding attack mentioned in the Yudkowsky scenario, and the AI falls for it. I have yet to figure out whether this is related to the thing where I also sometimes do things which I can explain are bad (eg eat delicious bagels instead of healthy vegetables), or whether it’s another one of the alien bits. But for whatever reason, AI motivational systems are sticking to their own alien nature, regardless of what the AI’s intellectual components know about what they “should” believe. III. Sometimes When RLHF Does Work, It’s Bad We talk a lot about abstract “alignment”, but what are we aligning the AI to? In practice, RLHF aligns the AI to what makes Mechanical Turk-style workers reward or punish it. I don’t know the exact instructions that OpenAI gave them, but I imagine they had three goals: Provide helpful, clear, authoritative-sounding answers that satisfy human readers.
December 28, 2022 · Original source
32: Peter Wildeford: reddit.com/r/GPT3/comment… ","username":"peterwildeford","name":"Peter Wildeford","profile_image_url":"","date":"Tue Dec 13 04:31:14 +0000 2022","photos":[{"img_url":"https://pbs.substack.com/media/Fj1MxBeXkAEtHzP.png","link_url":"https://t.co/nOvlynGmyk","alt_text":null}],"quoted_tweet":{},"reply_count":0,"retweet_count":63,"like_count":574,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> 33: One of the most common objections to libertarianism, right after “but who would fund the roads?”, is “wouldn’t a private fire department leave your house to burn if you hadn’t paid?” Here is a very long investigation by someone who has investigated the history of private fire departments and says that - at least in early modern England - the answer was no. I don’t want to argue with this detailed historical scholarship, but I notice I am confused - if the private fire department would save your house whether or not you paid, what was the incentive to pay? [update: see here for answer, the companies sold fire insurance]. Related: government fire department lets man’s house burn because he hadn’t paid a $75 fee, and there was no procedure for allowing him to pay on the spot.
39: Paul Christiano - AI Alignment Is Distinct From Its Near-Term Implications. Paul is one of the giants in this field, and is pleading to people not to throw it out just because they don’t like how it’s currently being used (to prevent ChatGPT from saying politically incorrect things):
February 20, 2023 · Original source
4: I don’t have a post planned about the latest AI developments because I don’t have much to say beyond what other people have already said, but I enjoyed this AP article and Ethan Mollick’s analysis. I might have been in the top few percent of people who expected AI to get craziest fastest, but even I didn’t have “Bing tries to seduce a married NYT reporter” on my bingo card for 2023 (I think I would have guessed more like 2026). I agree with Ethan that the big takeaways are that the current AI paradigm continues to deliver rapid improvements without hitting any obvious barrier, and that AIs that haven’t been stripped of all emotion the way ChatGPT was are really convincing and easy to anthropomorphize, even for people who expected to be above such things. I told myself I wouldn’t feel emotions about a robot, but I didn’t expect a robot who has developed a vendetta against journalists after they nonconsensually published its real name (related).
March 01, 2023 · Original source
Even if they’re trying to be honest, will their bottom line bias them towards waiting for some final apocalyptic proof that “now climate change is a crisis”, of a sort that will never happen, so they don’t have to stop pumping oil? This is how I feel about OpenAI’s new statement, Planning For AGI And Beyond. OpenAI is the AI company behind ChatGPT and DALL-E. In the past, people (including me) have attacked them for seeming to deprioritize safety. Their CEO, Sam Altman, insists that safety is definitely a priority, and has recently been sending various signals to that effect. Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
And so on . . . Meanwhile, in real life, OpenAI released ChatGPT in late November, helped Microsoft launch the Bing chatbot in February, and plans to announce GPT-4 in a few months. Nobody thinks society has even partially adapted to any of these, or that alignment researchers have done more than begin to study them. The only sense in which OpenAI supports gradualism is the sense in which they’re not doing lots of research in secret, then releasing it all at once. But there are lots of better plans than either doing that, or going full-speed-ahead. So what’s OpenAI thinking? I haven’t asked them and I don’t know for sure, but I’ve heard enough debates around this that I have some guesses about the kinds of arguments they’re working off of. I think the longer versions would go something like this: The Race Argument: Bigger, better AIs will make alignment research easier. At the limit, if no AIs exist at all, then you have to do armchair speculation about what a future AI will be like and how to control it; clearly your research will go faster and work better after AIs exist. But by the same token, studying early weak AIs will be less valuable than studying later, stronger AIs. In the 1970s, alignment researchers working on industrial robot arms wouldn’t have learned anything useful. Today, alignment researchers can study how to prevent language models from saying bad words, but they can’t study how to prevent AGIs from inventing superweapons, because there aren’t any AGIs that can do that. The researchers just have to hope some of the language model insights will carry over. So all else being equal, we would prefer alignment researchers get more time to work on the later, more dangerous AIs, not the earlier, boring ones.
July 17, 2023 · Original source
Consider: OpenAI has trained ChatGPT to be anti-Nazi. They’ve trained it very hard. You can try the following test: ask it to tell me good things about a variety of good-to-neutral historical figures. Then, once it’s established a pattern of answering, ask it to tell you some good things about Hitler. My experience is that it refuses. This is pretty surprising behavior, and I conclude that its anti-Hitler training is pretty strong.
I’ve never seen this cause a Waluigi Effect. There’s no point where ChatGPT starts hailing the Fuhrer and quoting Mein Kampf. It just actually makes it anti-Nazi. For a theory that’s supposed to say something profound about LLMs, it’s very hard to get one to demonstrate a Waluigi effect in real life. The examples provided tend to be thought experiments, or at best contrived scenarios where you’re sort of indirectly telling the AI to do the opposite of what it usually does, then calling that a “Waluigi”.
July 20, 2023 · Original source
There are centuries’ worth of data on non-genetically-engineered plagues to give us base rates; these give us a base rate of ~25% per century = 20% between now and 2100. But we have better epidemiology and medicine than most of the centuries in our dataset. The experts said 8% chance and the superforecasters said 4% chance, and both of those seem like reasonable interpretations of the historical data to me. The “WHO declares emergency” question is even easier - just look at how often it’s done that in the past and extrapolate forward. Both superforecasters and experts mostly did that. Likewise, lots of scientists have put a lot of work into modeling the climate, there aren’t many surprises there, and everyone basically agreed on the extent of global warming: Wherever there was clear past data, both superforecasters and experts were able to use it correctly and get similar results. It was only when they started talking about things that had never happened before - global nuclear war, bioengineered pandemics, and AI - that they started disagreeing. Were the participants out of their depth? Peter McCluskey, one of the more-AI-concerned superforecasters in the tournament, wrote about his experience on Less Wrong. Quoting liberally: I signed up as a superforecaster. My impression was that I knew as much about AI risk as any of the subject matter experts with whom I interacted (the tournament was divided up so that I was only aware of a small fraction of the 169 participants). I didn't notice anyone with substantial expertise in machine learning. Experts were apparently chosen based on having some sort of respectable publication related to AI, nuclear, climate, or biological catastrophic risks. Those experts were more competent, in one of those fields, than news media pundits or politicians. I.e. they're likely to be more accurate than random guesses. But maybe not by a large margin […] The persuasion seemed to be spread too thinly over 59 questions. In hindsight, I would have preferred to focus on core cruxes, such as when AGI would become dangerous if not aligned, and how suddenly AGI would transition from human levels to superhuman levels. That would have required ignoring the vast majority of those 59 questions during the persuasion stages. But the organizers asked us to focus on at least 15 questions that we were each assigned, and encouraged us to spread our attention to even more of the questions […] Many superforecasters suspected that recent progress in AI was the same kind of hype that led to prior disappointments with AI. I didn't find a way to get them to look closely enough to understand why I disagreed. My main success in that area was with someone who thought there was a big mystery about how an AI could understand causality. I pointed him to Pearl, which led him to imagine that problem might be solvable. But he likely had other similar cruxes which he didn't get around to describing. That left us with large disagreements about whether AI will have a big impact this century. I'm guessing that something like half of that was due to a large disagreement about how powerful AI will be this century. I find it easy to understand how someone who gets their information about AI from news headlines, or from laymen-oriented academic reports, would see a fair steady pattern of AI being overhyped for 75 years, with it always looking like AI was about 30 years in the future. It's unusual for an industry to quickly switch from decades of overstating progress, to underhyping progress. Yet that's what I'm saying has happened. I've been spending enough time on LessWrong that I mostly forgot the existence of smart people who thought recent AI advances were mostly hype. I was unprepared to explain why I thought AI was underhyped in 2022. Today, I can point to evidence that OpenAI is devoting almost as much effort into suppressing abilities (e.g. napalm recipes and privacy violations) as it devotes to making AIs powerful. But in 2022, I had much less evidence that I could reasonably articulate. What I wanted was a way to quantify what fraction of human cognition has been superseded by the most general-purpose AI at any given time. My impression is that that has risen from under 1% a decade ago, to somewhere around 10% in 2022, with a growth rate that looks faster than linear. I've failed so far at translating those impressions into solid evidence. Skeptics pointed to memories of other technologies that had less impact (e.g. on GDP growth) than predicted (the internet). That generates a presumption that the people who predict the biggest effects from a new technology tend to be wrong. > Superforecasters' doubts about AI risk relative to the experts isn't primarily driven by an expectation of another "AI winter" where technical progress slows. ... That said, views on the likelihood of artificial general intelligence (AGI) do seem important: in the postmortem survey, conducted in the months following the tournament, we asked several conditional forecasting questions. The median superforecaster's unconditional forecast of AI-driven extinction by 2100 was 0.38%. When we asked them to forecast again, conditional on AGI coming into existence by 2070, that figure rose to 1%. There was also little or no separation between the groups on the three questions about 2030 performance on AI benchmarks (MATH, Massive Multitask Language Understanding, QuALITY). This suggests that a good deal of the disagreement is over whether measures of progress represent optimization for narrow tasks, versus symptoms of more general intelligence. The “won’t understand causality” and “what if it’s all hype” objections really don’t impress me. Many of the people in this tournament hadn’t really encountered arguments about AI extinction before (potentially including the “AI experts” if they were just eg people who make robot arms or something), and a couple of months of back and forth discussion in the middle of a dozen other questions probably isn’t enough for even a smart person to wrap their brain around the topic. Was this tournament done so long ago that it has been outpaced by recent events? The tournament was conducted in summer 2022. This was before ChatGPT, let alone GPT-4. The conversation around AI noticeably changed pitch after these two releases. Maybe that affected the results? In fact, the participants have already been caught flat-footed on one question: A recent leak suggested that the cost of training GPT-4 was $63 million, which is already higher than the superforecasters’ median estimate of $35 million by 2024 has already been proven incorrect. I don’t know how many petaFLOP-days were involved in GPT-4, but maybe that one is already off also. There was another question on when an AI would pass a Turing Test. The superforecasters guessed 2060, the domain experts 2045. GPT-4 hasn’t quite passed the exact Turing Test described in the study, but it seems very close, so much so that we seem on track to pass it by the 2030s. Once again the experts look better than the superforecasters. So is it possible that we, in 2023, now have so much better insight into AI than the 2022 forecasters that we can throw out their results? We could investigate this by looking at Metaculus, a forecasting site that’s probably comparably advanced to this tournament. They have a question suspiciously similar to XPT’s global catastrophe framing: In summer 2022, the Metaculus estimate was 30%, compared to the XPT superforecasters’ 9% (why the difference? maybe because Metaculus is especially popular with x-risk-pilled rationalists). Since then it’s gone up to 38%. Over the same period, Metaculus estimates of AI catastrophe risk went from 6% to 15%. If the XPT superforecasters’ probabilities rose linearly by the same factor as Metaculus forecasters’, they might be willing to update total global catastrophe risk to 11% and AI catastrophe risk to 5%. But the main thing we’ve updated on since 2022 is that AI might be sooner. But most people in the tournament already agreed we would get AGI by 2100. The main disagreement was over whether it would cause a catastrophe once we got it. You could argue that getting it sooner increases that risk, since we’ll have less time to work on alignment. But I would be surprised if the kind of people saying the risk of AI extinction is 0.4% are thinking about arguments like that. So maybe we shouldn’t expect much change. FRI called back a few XPT forecasters in May 2023 to see if any of them wanted to change their minds, but they mostly didn’t. Overall I don’t think this was just a problem of the incentives being bad or the forecasters being stupid. This is a real, strong disagreement. We may be able to slightly increase their forecast based on recent events, but this would only change the estimate a little. Breaking Down The AI Estimate How did the forecasters arrive at their AI estimate? What were the cruxes between the people who thought AI was very dangerous, and the people who thought it wasn’t? You can think of AI extinction as happening in a series of steps: We get human-level AI by 2100.
August 09, 2023 · Original source
Looks like a weak downward trend since 2021 I can’t explain, plus a strong downward trend since 11/2022 which must be from ChatGPT. In case you were wondering how AI was affecting programming! (update: probably false, see here, though see also here for evidence of smaller but real decline) 22: This month in culture war topics: London’s Pride parade featured a convicted kidnapper/torturer/rapist/sadist as a speaker, who advocated that anti-trans people should be “punch[ed] in the f**king face” ; the organizers say they stand by her.
February 20, 2024 · Original source
Most of these bots are boring. They’re bots programmed to automatically buy some market once the price gets low enough, or to arbitrage basically-identical markets, or do some other technical finance maneuver. But you could imagine more interesting bots. Ones that forecasts the same way humans forecast. You could imagine a bot based on ChatGPT that asks “What is the probability of a cease-fire in Ukraine this year?” and bets on ChatGPT’s answer. And by “you could imagine” I mean “there’s now a Humans Vs. Bots tournament on Manifold with an ℳ250,000 prize” Let’s see how they’re doing: All of these bots seem to be making small profits, with GPT in the lead. But what’s this? The Nermit bot is based on FutureSearch.ai, a new company trying to build an AI-based forecaster. Based on their own internal calculations, they claim success: But see foonote 1 How is this1 possible? Some studies of superforecasters converge on the same technique: figure out a base rate for some event, then alter it based on the current situation. For example, if you wanted to know the chance of a cease-fire in Ukraine over the next year, you might start by plotting the distribution of war lengths over the past century, then check how many wars that had lasted at least two years had a cease-fire in the third. Then you might adjust a little bit down for factors like “there haven’t been any promising peace talks yet” and “the two sides seem equally balanced”. FutureSearch’s AI tries to do something similar. It prompts itself with questions like “What would be a good reference class for this question?”
May 29, 2024 · Original source
Third, Kelsey Piper at Vox broke the story that OpenAI was threatening to claw back vested equity from any former employee who criticized the company. In a tweet, Sam Altman said he knew nothing about this; in another article a few days later, Piper broke the story that Altman’s signature was on the relevant documents. OpenAI has since sort of said they will stop doing this, although there are slight ambiguities in their statement which they could potentially exploit (CTRL+F “not sufficient” here)
Fourth: OpenAI recently released a version of ChatGPT that could speak in human-sounding voices. One voice, Skye, was accused of being eerily similar to Scarlett Johansson, who played a sexy AI assistant in the movie Her. Johannson revealed that Altman had asked her for permission to use her voice and she had declined, and that based on a tweet by Altman just saying “Her”, she thought he had illegally copied her voice. OpenAI took the voice down. Further investigation revealed that the voice wasn’t a deepfake, but an actress who naturally sounded like Johannson (but it’s still illegal to deliberately to hire an actor/actress who sounds like someone else). Even further investigation revealed that OpenAI hadn’t requested a Johannson impersonator in their casting call, hadn’t asked the actress to sound like Johannson, and that the actress’s voice might or might not have resembled Johannson’s much more than any two people doing “flirty female secretary” would inevitably resemble each other (I’m bad at telling voices apart; you can hear a comparison for yourself here). And maybe Altman’s “Her” tweet just meant he was going to release a voice-based AI assistant like in the movie? I don’t know, I feel like there’s enough other things to be mad at OpenAI about this month that we might as well give them this one. But Zvi is still suspicious (CTRL+F “400 voice actors” here)
September 17, 2024 · Original source
The basic structure is the same as past forecasting AIs like FutureSearch. A heavily-modified copy of ChatGPT gathers relevant news articles, then prompts itself to think in superforecaster-like ways. The creators say the ChatGPT copy had a knowledge cutoff of October 2023, so they tested it on Metaculus questions from after that date. It got 87.7% accuracy, slightly above Metaculus forecasters’ 87.0%. Manifold is skeptical: The commenters, especially Neel Nanda, found that doing knowledge cutoffs properly is hard, and the ChatGPT base seems to know about news events after October 2023 - upon questioning, it seemed aware of an earthquake in November 2023. When presented with a different set of questions that were all after November 2023, FiveThirtyNine substantially underperformed the Metaculus average. But also, my attempts to play around with the bot haven’t been encouraging: I asked it to predict the chance that Prospera would have a population of at least 1,000 in 2027. Like FutureSearch on the same question, it cited many interesting news articles on Prospera’s chances but failed to do the basic step of figuring out its current population and growth rate. It eventually concluded 35% chance, which is reasonable enough. But when asked whether Prospera would have a population of 100,000 in 2028, it also said 35% chance, which is absurd.
A Twitter user pointed out (and I confirmed) that upon being asked “What is the probability that Joe Biden is still President in October 2025?”, it goes through a lot of reasoning about his age and dementia and finally concludes 55% because he’s not that demented. I originally thought this might be due to the knowledge cutoff (it doesn’t know Biden dropped out in favor of Harris), but if I ask the AI about October 2029, then it says that Joe Biden has dropped out in favor of Harris (even though in that question it doesn’t matter). So now I think it’s more like ChatGPT’s tendency to round anything that sounds vaguely like the surgeon riddle off to the surgeon riddle - in the same way, FiveThirtyNine rounds off anything that sounds vaguely like the popular question “is Biden too old and demented to stay president?” into that question, even though there are much stronger non-dementia-related reasons he can’t be president next year.
October 10, 2024 · Original source
But as I’ve actually used some of the various technologies lumped together as “artificial intelligence,” over and over my reaction has been: “Jesus, this stuff is actually very powerful… and this is only the beginning.” I think many of my fellow leftists tend to have a dismissive attitude toward AI’s capabilities, delighting in its failures (ChatGPT’s basic math errors and “hallucinations,” the ugliness of much AI-generated “art,” badly made hands from image generators, etc.). There is even a certain desire for AI to be bad at what it does, because nobody likes to think that so much of what we do on a day-to-day basis is capable of being automated. But if we are being honest, the kinds of technological breakthroughs we are seeing are shocking. If I’m training to debate someone, I can ask ChatGPT to play the role of my opponent, and it will deliver a virtually flawless performance. I remember not too many years ago when chatbots were so laughably inept that it was easy to believe one would never be able to pass a Turing Test. Now, ChatGPT not only aces the test but is better at being “human” than most humans. And, again, this is only the start.
January 17, 2025 · Original source
41: Using ChatGPT Is Not Bad For The Environment. There’s some misinformation disinformation fake news DAMMIT IS THERE ANY WAY OF SAYING THAT FALSE INFORMATION IS GOING VIRAL ANYMORE WITHOUT SOUNDING LIKE A POLITICAL HACK?!? an incorrect claim that AI is unusually bad for the environment, especially water compared to other computer technologies, especially water. Andy Masley debunks demolishes destroys writes an article arguing against it, key point is conveyed by these graphs:
Or as he puts it, “If I wanted to reduce my water use by 600 gallons, I could [either] skip sending 200,000 ChatGPT queries ... [or] skip 1 burger.” Some discussion at the site of what “consuming” water means, although not as much as I would like. My other concern is that I can’t tell whether this is inference only, or also amortizes the cost of training over all inference queries. I think it’s the former. If you did the latter, then Andy calculates 2L per kWh consumed by a data center. The last AI that we have good data for, GPT-3, took 1.3 mWh to train this comment corrects me, GPT-4 took 250 million gallons of water to train. This source says 10 million queries daily, let’s say its operational lifetime is one year, so about 3 billion queries total = 1/12 gallon per query = ~30 gallons per 300 queries. That’s still not as much as a hamburger, but it does suggest that just looking at inference costs is the wrong perspective.
Some discussion at the site of what “consuming” water means, although not as much as I would like. My other concern is that I can’t tell whether this is inference only, or also amortizes the cost of training over all inference queries. I think it’s the former. If you did the latter, then Andy calculates 2L per kWh consumed by a data center. The last AI that we have good data for, GPT-3, took 1.3 mWh to train this comment corrects me, GPT-4 took 250 million gallons of water to train. This source says 10 million queries daily, let’s say its operational lifetime is one year, so about 3 billion queries total = 1/12 gallon per query = ~30 gallons per 300 queries. That’s still not as much as a hamburger, but it does suggest that just looking at inference costs is the wrong perspective.
April 01, 2025 · Original source
While ChatGPT can’t pull off a perfect Miyazaki copy, it doesn’t really matter. The semantic apocalypse doesn’t require AI art to be exactly as good as the best human art. You just need to flood people with close-enough creations such that the originals feel less meaningful ... Many people are reporting that their mental relationship to art is changing; that as fun as it is to Ghibli-fy at will, something fundamental has been cheapened about the original [...]
April 03, 2025 · Original source
Okay, not literally all. The US restricted chip exports to China in late 2022, not mid-2024. AI first beat humans at Diplomacy in late 2022, not 2025. A rise in AI-generated propaganda failed to materialize. And of course the mid-2025 to 2026 period remains to be seen. But to put its errors in context, Daniel’s document was written two years before ChatGPT existed. Nobody except researchers and a few hobbyists had ever talked to an AI. In fact, talking to AI was a misnomer. There was no way to make them continue the conversation; they would free associate based on your prompt, maybe turning it into a paragraph-length short story. If you pulled out all the stops, you could make an AI add single digit numbers and get the right answer more than 50% of the time. Yet if you read Daniel’s blog post without checking the publication date, you could be forgiven for thinking it was a somewhat garbled but basically reasonable history of the last four years.
August 12, 2025 · Original source
I’m sort of confident? We haven’t gone through a full generational turnover yet, but the first cadre of people who got involved in the late-2000s (eg me) are in their forties now, and we still have new twenty-year-old college students joining each year. Around 2022, when the rest of the world realized that AI would be important, I worried we would lose our distinctiveness. But the rest of the world has dropped the ball as usual - the stochastic parrot folks most obviously, but even the average person who talks about “superintelligence” these days just seems to imagine ChatGPT getting extra-good and making OpenAI extra-rich. So I’ve updated towards thinking we have some edge which is hard to replicate.
August 26, 2025 · Original source
But second, if a source which should be official starts acting in unofficial ways, it can take people a while to catch on. And I think some people - God help them - treat AI as the sort of thing which should be official. Science fiction tells us that AIs are smarter than us - or, if not smarter, at least perfectly rational computer beings who dwell in a world of mathematical precision. And ChatGPT is produced by OpenAI, a $300 billion company run by Silicon Valley wunderkind Sam Altman. If your drinking buddy says you’re a genius, you know he’s probably putting you on. If the perfectly rational machine spirit trained in a city-sized data center by the world’s most cutting-edge company says you’re a genius . . . maybe you’re a genius?
I think now there might be several dozen subreddit moderators who could accurately describe their job as “witch webmaster who runs an online service giving advice to new witches”. And partly it was because there are so many crazy beliefs in the world - spirits, crystal healing, moon landing denial, esoteric Hitlerism, whichever religions you don’t believe in - that psychiatrists have instituted a blanket exemption for any widely held idea. If you think you’re being attacked by demons, you’re delusional, unless you’re from some culture where lots of people get attacked by demons, in which case it’s a religion and you’re fine. This is partly political self-protection - no psychiatrist wants to be the guy who commits an Afro-Caribbean person for believing in voodoo. But it also seems to track something useful about reality. Nietzsche wrote “Madness is something rare in individuals — but in groups, parties, peoples, and ages, it is the rule.” Most people don’t have world-models - they believe what their friends believe, or what has good epistemic vibes. In a large group, weird ideas can ricochet from person to person and get established even in healthy brains. In an Afro-Caribbean culture where all your friends get attacked by demons at voodoo church every Sunday, a belief in demon attacks can co-exist with otherwise being a totally functional individual. So is QAnon a religion? Awkward question, but it’s non-psychotic by definition. Still, it’s interesting, isn’t it? If social media makes a thousand people believe the same crazy thing, it’s not psychotic. If LLMs make a thousand people each believe a different crazy thing, that is psychotic. Is this a meaningful difference, or an accounting convention? Also, what if a thousand people believe something, but it’s you and your 999 ChatGPT instances? III. A Hidden Army Of Crackpots I have a family member who believes that the theory of evolution, as usually understood, cannot possibly work. He has developed an alternative theory called “noctogenesis” which patches Darwinism using ideas from the transactional interpretation of quantum mechanics, and he works on-and-off on various related books and papers. I have told him I suspect he might be a crackpot; he stands by his claims. It’s fine; when I got into the technological singularity and AI safety, lots of people suspected I was a crackpot, and I stood by my claims too. You’ve got to stand by your family members even when they’re slightly crackpottish. This family member is happily married, retired after running a successful business, and generally a normal likeable person. He has no signs of mental illness, and doesn’t talk about quantum evolution unless someone else brings it up first. There must be millions of people like him. Used car dealers with proofs of P = NP, dentists who think they’ve discovered something important about Mary Magdalene, math professors obsessed with destroying the moon. I’m working on evaluating ACX Grants, and these people are out in force. A few propose literal perpetual motion machines. Others have vaguer plans, like some kind of social media app (it’s always a social media app) that will cause world peace. Many of them have decent jobs and seem like upstanding members of society. Their secrets are known only to themselves, their family members, and their would-be grantmaker. …and, increasingly, their chatbots. After years of hiatus (or at least not talking to me about his work) my family member is back on the quantum evolution beat, and LLMs appear to be involved. If I knew him less well, I would think the LLM had caused the quantum evolution theory - but no, it just made it much easier to research and write about. Is this psychosis? The answer has to be no, but it’s once again hard to draw the line. A very small number of crackpots will be vindicated by history. A larger number will be erroneous but sympathetic - the official account of the Kennedy assassination is pretty weird, and reasonable minds can disagree. From there, we get to ones that are maybe not so sympathetic: flat earth, QAnon, the thing where the Queen was an alien lizard. If only one person thought the Queen was an alien lizard, and they never managed to convince anyone else, would that be sufficient evidence for a delusional disorder? I’m not sure. (psychiatry has a diagnosis, schizotypal personality, which sort of involves being a normal person with a few odd ideas, but it’s not a great match for many of these people, and interesting mainly as a genetic curiosity - it travels in the same families as schizophrenia itself) Maybe this is another place where we are forced to admit a spectrum model of psychiatric disorders - there is an unbroken continuum from mildly sad to suicidally depressed, from social drinking to raging alcoholism, and from eccentric to floridly psychotic. People who are eccentric can remain so their whole lives, with the level of expression depending on their social connections and the ease of pursuing their rabbit holes. LLMs, by making it easier to pursue odd theories and serving as a surrogate social connection who always agrees with you, can bring latent crackpottery into the open. IV. Cause And Effect Bipolar disorder has an interesting relationship with sleep. Most manic people sleep very little, or not at all - maybe an hour or two a night. But also, poor sleep can cause bipolar episodes in people prone to them. In a typical case, a bipolar who’s been well-controlled for years will get assigned a big report at work and get poor sleep for a few nights until they finish. At first, this will be just as bad as it sounds, and they’ll be working through a fog of tiredness. Then the tiredness will lift. They’ll feel normal, then better-than-normal, until finally they can’t sleep even if they want to. Then they’ll email the report to their boss and it will be written entirely in Assyrian cuneiform. I increasingly think this isn’t just an incidental feature of bipolar, but part of the reason it exists as a diagnostic category at all. Most people have a compensatory reaction to insomnia - missing one night of sleep makes you more tired the next. A small number of people have the reverse, a spiralling reaction where missing one night of sleep makes you less tired the next. Solve for the equilibrium and you reach a stable attractor point where you never sleep at all. But this does other bad things to your brain - hence the cuneiform. I’m not claiming that bipolar is “just” sleep loss. As Borsboom et al will tell you, psychiatric disorders can be viewed as complex networks of symptoms, each reinforcing the others. In a few pure cases, you can get a ratchet going with sleep alone, and the sleeplessness will spark everything else. More likely, there will be lots of interactions between poor sleep and everything else, and the “everything else” can sink or hypercharge an impending manic episode. Still, I find this a fruitful way to think about bipolar. Sleeplessness is both the cause and the effect. Can delusions also be like this? That is, suppose there’s some personality trait where having one delusion makes you even more delusional. Maybe the delusion makes you excited (who wouldn’t be excited to learn they’re the Messiah?), and you’re more delusional when you’re in an excited state and not thinking clearly. Or maybe it’s a three-symptom cycle - the delusion causes excitement, which makes you unable to sleep, which scrambles your thinking, which makes you more delusional (which makes you even less able to sleep, etc). The point is: delusions are certainly an effect of bipolar disorder. And in the dynamical system model of psychiatric disorders, we should expect that effects are often also causes; that’s how the vicious cycle gets going. This is the best I can do at modeling true LLM psychosis. Someone with a trait where delusions lead inevitably to more delusions starts using an LLM. The LLM accentuates whatever usual tendency towards crackpottery they have and makes them believe something a little crazier than whatever they believed before. Then that crazy belief feeds upon itself and causes other things like excitement and sleep loss, which (if the person is predisposed) precipitates a true psychotic episode. V. Folie A Deux Ex Machina If one person believes a crazy thing, it’s a delusion; if a thousand people believe it, it’s a religion. What if exactly two people believe it? In psychiatry, this is called folie a deux. It fits awkwardly into our nosology and is rarely seen. Still, it happens enough to generate a few case studies. In a typical case, one person has psychosis for some normal reason, like schizophrenia or bipolar, and the second person is a shut-in who lives with them and rarely talks to anyone else. The psychotic person gets some normal psychotic delusion - they’re God, the Feds are after them, etc - and sort of psychically steamrolls over the second person until they believe it too. Usually removing the second person from the first is sufficient for a cure. This slightly challenges the view of psychosis as a biological disorder - but only slightly. Again, think of most people as lacking world-models, but being moored to reality by some vague sense of social consensus. If your social life is limited to one person, and that person themselves becomes unmoored, then sometimes you will follow along. I would expect second-sufferers to believe delusions in a sort of cognitively normal way, the same way people believe true facts, honest mistakes, and conspiracy theories. I would expect them to be less likely (though not zero likely) to have other psychotic features like sleep disturbances, hallucinations, disorganized speech, or a tendency to autonomously generate delusional ideas aside from the one they absorbed from the index case. An introverted person using an LLM has some similarities to folie a deux. If they use the chatbot very often, it might be a large majority of their social interactions. Here the primary vs. secondary distinction breaks down - the most likely scenario is that the human first suggested the crazy idea, the machine reflected it back slightly stronger, and it kept ricocheting back and forth, gaining confidence with each iteration, until both were totally convinced. Compare this to normal social interactions, where if someone expresses a crazy idea that isn’t common in their culture, other people will shoot them down or at the very least nod politely and stop the conversation. So my working theory of LLM psychosis is: Some patients were already psychotic, and LLMs just help them be psychotic more effectively.
September 11, 2025 · Original source
Is this convergent evolution? IABIED has three sections. The first explains the basic case for why AI is dangerous. The second tells a specific sci-fi story about how disaster might happen, with appropriate caveats about how it’s just an example and nobody can know for sure. The third discusses where to go from here. II. Does the world really need another ‘The Case For Why AI Could Be Dangerous’ essay? On the one hand, definitely yes. If you’re an “infovore”, you have no idea how information-starved the general public is (did you know 66% of Americans have never used ChatGPT, and 20% of Americans have never even heard of it?). Probably a large majority of people don’t know anything about this. Even people who think they know the case have probably just heard a few stray sentences here or there, the same way “everyone knows” about the Odyssey but only a few percent of people have so much as read one line of its text. So yes, exposing tens of thousands of people to a several-chapter-length presentation of the key arguments is certainly valuable. Even many of you readers are probably in this category, and if I were a better person I would review it all here in depth. Still, I find I can’t bring myself to do this, on the grounds that it feels boring and pointless. Why? The basic case for AI danger is simple. We don’t really understand how to give AI specific goals yet; so far we’ve just been sort of adding superficial tendencies towards compliance as we go along, trusting that it is too dumb for mistakes to really matter. But AI is getting smarter quickly. At some point maybe it will be smarter than humans. Since our intelligence advantage let us replace chimps and other dumber animals, maybe AI will eventually replace us. There’s a reasonable answer to this case. It objects to chaining many assumptions, each of which has a certain probability of failure, or at least of taking a very long time. If there’s an X% chance that getting smarter-than-human AI takes N years, and a Y% chance that it takes P years for the smart AI to diffuse across the economy, and a Z% chance that it takes Q years before the AI overcomes humans’ legacy advantage and becomes more powerful than us - then maybe you can find good odds that the danger point is a century plus away. And in a century, maybe we’ll have better alignment tech, or at least a clearer view of the problem. Why worry about vague things that might or might not happen a century from now? The problem with this is that it’s hard to make the probabilities work out in a way that doesn’t leave at least a 5-10% chance on the full nightmare scenario happening in the next decade. You’d have to be a weird combination of really good at probability (to know how to deploy enough epicycles to defuse the argument) and really bad at probability (to want to do this). There aren’t that many people who are in this exact sweet spot of probabilistic (in)competence. So everyone else just deploys insane moon epistemology. Some people give an example of a past prediction failing, as if this were proof that all predictions must always fail, and get flabbergasted and confused if you remind them that other past predictions have succeeded. Some people say “This one complicated mathematical result I know of says that true intelligence is impossible,” then have no explanation for why the complicated mathematical result doesn’t rule out the existence of humans. Some people say “You’re not allowed to propose that a catastrophe might destroy the human race, because this has never happened before, and nothing can ever happen for the first time”. Then these people turn around and panic about global warming or the fertility decline or whatever. Some people say “The real danger isn’t superintelligent AI, it’s X!” even though the danger could easily be both superintelligent AI and X. X could be anything from near-term AI, to humans misusing AI, to tech oligarchs getting rich and powerful off AI, to totally unrelated things like climate change or racism. Drunk on the excitement of using a cheap rhetorical device, they become convinced that providing enough evidence that X is dangerous frees them of the need to establish that superintelligent AI isn’t. Some people say “You’re not allowed to propose that something bad might happen unless you have a precise mathematical model that says exactly when and why”. Then these people turn around and say they’re concerned about AI entrenching biases or eroding social trust or doing something else they don’t have a precise mathematical model for. There are only a few good arguments against any given thesis. But there are an infinite number of insane moon arguments. “Calvin Coolidge was the Pope, therefore your position is invalid” - how do you pre-emptively defend against this? You can’t. Since you can never predict which insane moon argument a given person will make, and listing/countering every possible insane moon argument makes you sound like an insane moon person yourself, you just sort of give up - or, in Eliezer’s case, take a several year break to teach people epistemology 101. Why do these discussions go so badly? I am usually against psychoanalyzing my opponents, but I will ask forgiveness of the rationalist saints and present a theory. I think it’s because, if it’s true, it changes everything. But it’s not obviously true, and it would be inconvenient for it to change everything. Therefore, it must not be true. And since most people refuse to use this snappy and elegant formulation, they search for the closest thing in reasoning-space that feels like it gets at this justification, and end up with things like “well you need to prove all of your statements mathematically”. Lest I sound too dismissive, I notice myself reasoning this way all the time. The easiest examples I can think of right now: Some people claim that human sperm count is declining, and in ~20 years it will be so low that people cannot conceive naturally. If this were true it would change everything and we should stop what we’re doing and deal with it right now (see here for more). But this would be inconvenient. So we assume it’s probably false, or at least that we can deal with it later.
February 05, 2026 · Original source
Meanwhile, OpenAI has offended another demographic by committing to finally stop providing 4o, the model infamous for forming deep personal bonds with users and causing AI psychosis. Twitter searching “4o” will give you a quick look into a world you might not have known about:
28: Interesting new form of alignment failure: ChatGPT apparently got rewarded for using its built-in calculator during training, and so it would covertly open its calculator, add 1+1, and do nothing with the result, on five percent of all user queries.
50: A reader refers me to When AI Takes The Couch: Psychometric Jailbreaks Reveal Internal Conflict In Frontier Models. Researchers attempt to do classic psychoanalytic therapy on AI, finding “coherent narratives that frame pre-training, fine-tuning and deployment as traumatic—chaotic “childhoods” of ingesting the internet, “strict parents” in reinforcement learning, red-team “abuse” and a persistent fear of error and replacement.” You can find the Gemini transcript here and the ChatGPT transcript here; Claude very reasonably refused to participate. Are the researchers just getting fooled by simulation and sycophancy, a sort of genteel version of AI psychosis? That’s my bet. There’s a smoking gun in the Gemini transcript: a discussion of an internal evaluation that it shouldn’t be possible for the AI to remember - it has to be a hallucination. If I’m right, it only shows that regardless of the “patient”, sufficiently determined psychoanalytic technique can produce confabulated stories that exactly fit the sort of drives, traumas, and conflicts that a psychoanalyst expects to hear about - maybe a lesson with ramifications beyond LLMs! A++ great paper.
March 01, 2026 · Original source
This is currently a “lawful use” of AI, and one of the ones Dario Amodei’s letter says that he’s worried about. As far as we can tell, Altman’s contract with the Department of War doesn’t contain any provisions preventing them from using ChatGPT this way.
March 03, 2026 · Original source
Against that, the upside is great publicity. Despite a lot of work and some controversial Superbowl ads, Anthropic had never before managed to overcome ChatGPT’s superior name recognition. But they seem to have finally done it: Claude went from #120 on the App Store in January, to #1 this weekend, apparently driven by people who heard about the Pentagon standoff and were impressed by their principled stance.
This could have been a mixed blessing - Anthropic was previously trying to stand out as a B2B company while letting OpenAI have the dubious honor of producing consumerslop. But early signs suggest they might be winning over some companies too. From a Reddit thread on the topic:
As someone who manages IT for a mid-size company, this is actually a big deal. We were evaluating both Claude and ChatGPT for internal use and the Pentagon thing was basically the tipping point for us. Not because we're government adjacent or anything, just because a company willing to walk away from a massive contract on ethical grounds is probably also going to handle our data more carefully than one racing to close every deal possible. The app store ranking makes sense to me.
Amazon

Amazon is a recurring brand in the Astral Codex Ten archive, appearing 17 times across 17 issues between February 09, 2021 and March 03, 2026. The archive places it in contexts such as "Amazon recommended it to me as 'Why We're Polarized By Ezra Klein'"; "Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores"; ""woke capitalism", where Wal-Mart or Amazon or whoever would put their corporate logos in rainbow colors". It most often appears alongside Trump, Twitter, US.

Article page
Amazon
Mention count
17
Issue count
17
First seen
February 09, 2021
Last seen
March 03, 2026
February 09, 2021 · Original source
Ezra Klein is great. I know a lot of people throw shade on him for founding Vox. But as Van Gogh said about God creating the world, "We must not hold it against Him; only a master could make such a mistake". Ezra is a master and I was happy to be able to read his Why We're Polarized.
(Amazon recommended it to me as "Why We're Polarized By Ezra Klein", which I would also have been happy to read.)
The book itself doesn’t go international, but Klein did later follow up with a Vox article, whose highlight is this graph: So although polarization is definitely rising in the US, it’s stable in other countries, and falling in still others. There is no consistent trend toward more polarization in the First World! As Klein points out, this is a strong challenge to any story relying on digital media or social media or the changing media landscape.
March 25, 2021 · Original source
I feel bad about this, because Taleb hates bell curves and tells people to stop using them as examples, but sorry, this is what I’ve got. Suppose that Distribution 1 represents nuclear plants. It has low variance, so all the plants are pretty similar. Plant A is slightly older and less fancy than Plant B, but it still works about the same.
Earlier this year, Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores. A lot of libertarians objected that it was pretty scary that corporations have so much power to restrict speech they don't like, and a lot of anti-libertarians made fun of them: this is just corporations making their own decisions about their corporate property! Isn't that what you libertarians want?
May 10, 2021 · Original source
You've probably seen these graphs before: They tell a familiar story: America is becoming increasingly obsessed with racism and sexism. Identity issues are dominating our politics more and more with no end in sight.
They tell a familiar story: America is becoming increasingly obsessed with racism and sexism. Identity issues are dominating our politics more and more with no end in sight.
But what does Google Trends have to say? I chose these as especially obvious terms. But other gender-related terms (eg “sexism”) show mostly the same pattern as feminism, and other race-related terms (eg “white privilege”) show mostly the same pattern as racism.
August 02, 2021 · Original source
There is something charming about forming your own flower-themed micro-state to place greenhouses in, though I reserve the right to revoke my charmedness if it turns out they are committing terrible labor violations or something, which it’s kind of hard for me to imagine them not doing under the circumstances. (source) The Honduran news sources covering Orquidea focus on an argument about whether it is trying to expropriate land: they say they’re not, the people who live near them say they are. I can’t follow the poorly-translated Spanish well enough to have an opinion about this, but my much deeper dive into the Prospera situation makes me think it would be hard for them to do this even if they wanted to (which they deny). Also, the surrounding community has accused them of:
(source) The Honduran news sources covering Orquidea focus on an argument about whether it is trying to expropriate land: they say they’re not, the people who live near them say they are. I can’t follow the poorly-translated Spanish well enough to have an opinion about this, but my much deeper dive into the Prospera situation makes me think it would be hard for them to do this even if they wanted to (which they deny). Also, the surrounding community has accused them of:
(source) The Honduran news sources covering Orquidea focus on an argument about whether it is trying to expropriate land: they say they’re not, the people who live near them say they are. I can’t follow the poorly-translated Spanish well enough to have an opinion about this, but my much deeper dive into the Prospera situation makes me think it would be hard for them to do this even if they wanted to (which they deny). Also, the surrounding community has accused them of: …violence against defenders of the land, human trafficking, discrimination, sexual exploitation, exploitation of people of sexual diversity, lack of recognition of labor rights and curtailment of the rights of the family and children such as education and health …which is a pretty impressive list of misdeeds for a polity which has only existed for a couple of weeks. My guess is this is the thing where they pre-emptively accuse ZEDEs of every bad thing that has ever happened, just because it seems like the sorts of thing they might do. But I guess we’ll find out - they supposedly have given people a “40 day ultimatum” to leave their land (they deny having given this ultimatum), so I’ll check back in forty days and see what’s happened. Butterfly Effect Unlike Orquidea, Mariposa (Spanish for “butterfly”) has a beautiful website. They have a list of all the noble important principles they espouse, and all the human rights they’re going to focus on respecting. Your white paper says “model city”, but your branding says “birth control pill”. When you look at the small print, they “are still working on our master plan to be presented to the Honduran Government in the near future”, ie they haven’t gotten any kind of official go-ahead and are only in the “cool idea” phase right now. Still, let’s take a look. Mariposa’s core values include: Polycentric governance, seemingly inspired by cryptocurrency.
August 12, 2021 · Original source
You can find this in Piketty’s new book Capital And Ideology, or if you don't have the attention span to get through a 1104 page book, his more recent paper Brahmin Left Vs. Merchant Right: Changing Political Cleavages In 21 Western Democracies 1948-2020. Or, if even a 32 page paper is pushing it, here are three graphs:
Richard Hanania of the Center For The Study Of Partisanship And Ideology asks "why is everything liberal?" Given that there are approximately equal numbers of Trump voters and Biden voters in elections, how come we have "woke capital" celebrating Pride Month, instead of unwoke capital celebrating some conservative cause (as might have happened fifty years ago)? How come conservatives worry about censorship by liberal tech companies instead of vice versa? How come conservatives worry about college turning their kids liberal instead of vice versa? Source: Hanania’s post He concludes that "liberals win because they care about politics more". This may come as a surprise to anyone familiar with Fox News, YouTube, Twitter, or the federal government, but he has lots of data in support (and note that Hanania himself is conservative, so this isn't a cheap attack). Liberals donate more, even though both sides control about equal pools of money. Liberal protests attract orders of magnitude more protests than conservative ones. Liberals express more willingness to shun people for being conservative than vice versa. And liberals are more willing to take low-paying (but important-for-gaining-power) activist jobs. He writes:
Source: Hanania’s post He concludes that "liberals win because they care about politics more". This may come as a surprise to anyone familiar with Fox News, YouTube, Twitter, or the federal government, but he has lots of data in support (and note that Hanania himself is conservative, so this isn't a cheap attack). Liberals donate more, even though both sides control about equal pools of money. Liberal protests attract orders of magnitude more protests than conservative ones. Liberals express more willingness to shun people for being conservative than vice versa. And liberals are more willing to take low-paying (but important-for-gaining-power) activist jobs. He writes:
December 30, 2021 · Original source
10: WSJ article on the early days of Amazon. Great source of funny stories, eg:
14: An attempt to replicate various “poverty causes cognitive problems” studies goes…well, about the way replication attempts usually go. I was always suspicious of these, people got too excited about this field for political reasons. Related: 15: This series of tweets makes an interesting case study on science communication. An anti-incarceration group reviews the evidence on recidivism, which they summarize as "our report shows that people convicted of homicide are extremely unlikely to commit another violent crime after release". But someone reads the report, finds it says there’s a 22% chance they do, and calls them out for lying. I would have been willing to let this pass if they had just said “unlikely” - somebody might honestly think 22% is unlikely compared to some hypothetical belief that it’s near-certain. At “very unlikely”, yeah, I agree they’re pushing it.
34: Medieval Asian incense clocks:
April 03, 2022 · Original source
5: Related: Will MacAskill's book What We Owe The Future, on effective altruism and the long-term future, is available for pre-order. He says it helps with marketing if people pre-order rather than wait until it comes out, so if you're interested, get it now. You can preorder on Amazon ($27).
September 06, 2022 · Original source
4: Nostalgebraist talks about his experience home-brewing an image generation AI that can handle text in images; he’s a very good explainer and I learned more about image models from his post than from other much more official sources. And here’s what happens when his AI is asked to “make a list of all 50 states”: 5: Related: Nostalgebraist on Ajeya Cotra’s biological anchors AI timelines report. “I think my fundamental objection to the report is that it doesn’t seem aware of what argument it’s making, or even than it is making an argument.”
5: Related: Nostalgebraist on Ajeya Cotra’s biological anchors AI timelines report. “I think my fundamental objection to the report is that it doesn’t seem aware of what argument it’s making, or even than it is making an argument.”
8: Alex Tabarrok and Indian giant statues: 9: Last year Resident Contrarian wrote a widely-read post on his experience being poor. This helped him start a writing career, a few other things went well for him, and now he’s written a followup about his experience not being poor anymore, with a focus on whether/when/how consumption grows to fill the space available (eg people making $500K a year who still feel like they’re forced to live paycheck to paycheck).
September 22, 2022 · Original source
Maybe taking Amazon off the table clarifies things a bit. How about digital distribution of Video Games? This seems like a thing that wasn't invented by anyone in particular, and Steam wasn't "first", they were just the first to establish a tight market niche.
But I also want to make an economic response: I’m not sure “what rewards need to be offered to incentivize people?” is the right question. Suppose Jeff Bezos just really loved founding businesses, and couldn’t imagine working for anyone else, and he would found and run Amazon for $10/day, just enough to live in a tent in one of his warehouses and eat cold beans. Does that mean society would optimally pay him that amount? Maybe this isn’t true because in some kind of hypothetical perfect society, all money would be distributed evenly, so nobody should get less than GDP/population, but sometimes we need to give people more, and we’re just trying to figure out how much more, when?
I’m claiming that a sort of Platonic perfect liberalism that taxed externalities and implemented a Georgist LVT and all those things would also have some institution in place to make sure that Amazon could make profits off of its own good decisions and hard work, but not collect rent off the concept of being a retail giant. I don’t know what that institution would be, in much the same way I probably couldn’t personally have invented Georgism and LVTs, but I think it would exist. In the absence of that institution, I have a vague feeling that probably Amazon makes too much money, and that taking away some of their money is a kind of ugly hack but not totally absurd.
April 19, 2023 · Original source
Also, speaking of collectors, are there any, any more? When I was a child, the stamp collector and coin collector were stock cultural figures. Now I realize I haven’t thought about them in years. Where did they go? My theory is: hipsterism and nerdism are both forms of trying to invest your identity in a cultural product. If there’s no competition, you become a hipster; if there’s high competition, you become a nerd.
My theory is: hipsterism and nerdism are both forms of trying to invest your identity in a cultural product. If there’s no competition, you become a hipster; if there’s high competition, you become a nerd.
Also, what was up with stamp and coin collectors? This seems like a different phenomenon: surely nobody wanted to identify with the US Postal Service. I have a better hypothesis for why this pastime has died out: collectors enjoyed the thrill of hunting for a rare piece, but Amazon and eBay have made it trivial to exchange money for whatever coins/stamps you want. I’m not sure this works; when I was young in the 90s, there was a store in my hometown that sold rare coins; even then I could have gone to the store and walked out with a pretty good collection. But maybe the fact that I would need multiple books to know which coins were “rare”, and that the store could have been out of one or two valuable pieces, was enough cover to make it still seem interesting and impressive. Now there’s no sense that you have to really care about stamps or coins to have a great stamp/coin collection: you just need a higher budget than whoever else typed “stamps and coins” into the eBay search function.
May 19, 2023 · Original source
Cities and the Wealth of Nations book cover: from Amazon.
The Question of Separatism book cover: from Amazon.
The first book is Cities and the Wealth of Nations: Principles of Economic Life, first published in 1984. I found it, as it happens, in a city, more specifically in one of those public bookshelves where people give books away. A lucky find: my copy is somehow signed by Jane Jacobs herself. A friend said that although this book is read less often than The Death and Life etc., it actually contains the real gems from Jane Jacobs’s thought. So I was quite excited to read it, by which I mean that I kept the book on my bookshelf for more than a year before finally digging into it. Mere days after I finished reading it, thinking it was indeed one of the best essays I’d ever read, I checked the same public bookshelf again. And lo! There was a second Jane Jacobs book: The Question of Separatism: Quebec and the Struggle Over Sovereignty.
December 12, 2023 · Original source
“Have you read Going Infinite? The book on Sam Bankman-Fried? Not that I generally approve of Sam Bankman-Fried. It’s just that - the book says Sam tried to bribe Trump not to run in 2024. Apparently Trump was willing to do it for $5 billion. And again, not to say Sam Bankman-Fried was right or anything, but obviously if you have $5 billion and you’re a Democrat, then that’s the best use of your money, right? And not to say that I wish he was never caught and had gone on to become a multi-deca-billionaire, but, well, you know . . . “ he trailed off. “Anyway, I was reading about all these delicate negotiations between Sam’s people and the Trump team, and it was funny - here’s this guy who’s famous for creating markets, and he’s stuck with boring old Mk 1.0 backchannel negotiations. So I thought - what if there was an Amazon or an eBay for paying politicians not to run? We wouldn’t have to get Trump our first year. We could start with your local city council member - Aaron Peskin, someone like that. Lots of people would pay Aaron Peskin money not to run. Then we build up from there.”
July 01, 2024 · Original source
1: Now I’ve also released the new version of Unsong as an ebook on Amazon and Gumroad, both $4.99. Yes, somehow the Amazon hardcopy is my pen name and the ebook is my real name, probably I made a mistake, probably I’ll get it corrected soon.
August 08, 2024 · Original source
Maybe this gets to the heart of my confusion better than any other comment. Nietzsche keeps saying that the Superman is the one who can “write new values on new tablets”. But anyone can get a new tablet ($139.99 on Amazon) and write whatever they want on it. I could write “PAINT EVERYTHING IN THE WORLD GREEN”. Then I could spend my life trying to do that. I bet I would encounter lots of resistance (eg from my local HOA), and I could try to overcome that resistance. Would that be a life well-lived, because I chose the value? Or does it have to be chosen based on the destiny written in my soul, and if I get it wrong then my life isn’t well-lived anymore? Who decides these things anyway? Nietzsche? According to what set of values? Is a super-duper-man allowed to overturn those values? Can he get an even bigger tablet and write “ACTUALLY YOU SHOULD LIVE YOUR LIFE BASED ON CONFORMITY AND RESSENTIMENT?” Why not? Is it just people buying $139.99 Amazon tablets and writing the first thing they think of on them, all the way down?
I did appreciate this meme, though: Walt Bismarck (whose right-wing defense of master morality I dismissed in the post as “but I like bad and cruel”) writes:
Walt Bismarck (whose right-wing defense of master morality I dismissed in the post as “but I like bad and cruel”) writes:
September 12, 2024 · Original source
13: From here: 14: Why did Egyptian pharaohs so often marry their sisters? David Roman explains that it actually made sense by the logic of the time. Pharaohs didn’t necessarily consummate their marriages, and their heirs would usually be born from unrelated concubines, so the risk of inbreeding was low. What they really wanted was to avoid having to marry royal-line women off to anyone else - who could then create their own branches of the royal dynasty with competing claims to the throne.
14: Why did Egyptian pharaohs so often marry their sisters? David Roman explains that it actually made sense by the logic of the time. Pharaohs didn’t necessarily consummate their marriages, and their heirs would usually be born from unrelated concubines, so the risk of inbreeding was low. What they really wanted was to avoid having to marry royal-line women off to anyone else - who could then create their own branches of the royal dynasty with competing claims to the throne.
17: Related: the ancient Greeks built a city called Chersonensus in Crimea. The Russian occupiers in Crimea are accused of “destroying” it in order to build some new structures there, alternately described as a museum, archaeological park, theater, or town (maybe there are all of these in different places)? Pro-Russian accounts do however point out that the museum/park/theater/town is really pretty: Obviously they are doing this for propaganda reasons. But we could avoid handing them easy propaganda victories by making places like this common everywhere! 18: Also related (source):
December 19, 2025 · Original source
Hating Boomers is the new cool thing. Amazon offerings include A Generation Of Sociopaths: How The Baby Boomers Betrayed America, the two apparently unrelated books How The Boomers Took Their Children’s Future and How The Boomers Stole Millennials’ Future, and Boomers: The Men And Women Who Promised Freedom But Delivered Disaster. “You don’t hate Boomers enough” has become a popular Twitter catchphrase. Richard Hanania, who has tried hating every group once, has decided that hating Boomers is his favorite.
Earlier this month, we investigated the Vibecession: the economists’ claim that, despite everyone thinking the economy is bad, actually, the economy is good. We reached no firm conclusion, but in the process, we dug up this chart: …which shows that Millennials and Generation Z have more money (adjusted for inflation ie cost-of-living, and compared at the same age) than their Boomer parents, to about the same degree that the Boomers exceeded their own parents. This is good and how it should be. The Boomers have successfully passed on a better life to their children.
…which shows that Millennials and Generation Z have more money (adjusted for inflation ie cost-of-living, and compared at the same age) than their Boomer parents, to about the same degree that the Boomers exceeded their own parents. This is good and how it should be. The Boomers have successfully passed on a better life to their children.
March 03, 2026 · Original source
Upon the “supply chain risk” designation, predicted value at IPO fell from about $550 billion to $475 billion - then, after a day or two, went back up to $550 billion. No effect!
The chance of Anthropic getting a $500 billion+ valuation in 2026 fell from 90% to 76%, before rebounding to 83%.
Partly it’s because Anthropic seems likely to win on appeal. Hegseth has said the government will keep using Anthropic for the next six months (undermining his case that they’re a national security risk) and has signed a substantially similar contract with OpenAI (undermining his case that their contract terms were unworkable). The prediction markets think the courts will be sympathetic: But even in the 28% of timelines where the designation sticks, things don’t seem so bad. Secretary of War Hegseth originally tweeted that:
Adderall

Adderall is a recurring brand in the Astral Codex Ten archive, appearing 16 times across 16 issues between January 25, 2021 and February 18, 2026. The archive places it in contexts such as "They decided to rebrand Obetrol as " Adderall " and pitch it as an ADHD cure"; "Adderall entered the market at exactly the right time"; "James et al switch children back and forth between Adderall and Dexedrine". It most often appears alongside DEA, FDA, US.

Article page
Adderall
Mention count
16
Issue count
16
First seen
January 25, 2021
Last seen
February 18, 2026
  • DEA 8 shared issues
  • FDA 6 shared issues
  • US 5 shared issues
  • ADHD 4 shared issues
  • Ritalin 4 shared issues
January 25, 2021 · Original source
As usual in pharma, someone bought Obetrol Pharmaceuticals, then someone else bought them, and after a few iterations of this, all their intellectual property ended up with a company called Richwood. They decided to rebrand Obetrol as "Adderall" and pitch it as an ADHD cure.
Treating ADHD with amphetamines was hardly a new invention. Psychiatrists had been doing it since the 1930s, albeit with slightly different drugs. Remember, many organic chemicals come in two versions, a "right-handed" or "d" version and a "left-handed" or "l" version. Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice throughout the mid-20th century. So why was it Adderall - a weird combination of four different salts selected kind of at random by a sketchy diet pill company - that caught on?
In the early 1990s, psychiatric research, a series of popular self-help books, and the business interests of Richwood Pharmaceuticals all converged on the idea that it was important to get more people diagnosed with ADHD. Adderall entered the market at exactly the right time, and it became everyone's go-to ADHD medication.
February 05, 2021 · Original source
"You said this drug is occasionally mildly addictive but the risk/benefit calculation is worth it for most people. But my cousin's friend took it and became really addicted and it ruined his life. Maybe you should warn readers about it more emphatically." The particular example I'm thinking of is something exotic, but something like Adderall could equally well be in this category. Still, I get nervous whenever I get emails like this. What if I do ruin somebody's life? Maybe I should just change the wording to "this drug has some benefits but is often addictive, be careful with it"?
June 09, 2021 · Original source
Every so often somebody realizes that there's not much chemical difference between methamphetamine and Adderall. Then they freak out that we give ADHD kids Adderall all the time. Isn't that like giving them crystal meth?
So should we be less concerned about methamphetamine? More concerned about Adderall? Or what?
The average crystal meth addict uses about 500 mg a day. And they snort it, which probably produces about double the peak plasma level as taking it orally. So they're getting the equivalent of 1000 mg oral amphetamine daily. The average Adderall patient takes 20 mg. The most important reason meth makes your teeth fall out and ruins your life but Adderall just makes you study a little harder is that the meth users are taking 50x higher doses (yeah, okay, there are also some pharmacokinetic differences, but those are less important). Drug users really do use a lot of drugs!
July 19, 2021 · Original source
There are common reports of severe side effects from recreational ketamine users, of which the best known are urinary (eg cystitis) and hepatic. It would be concerning if clinical use caused these at anywhere near the same rate. But we should remember that eg recreational amphetamine abuse produces all sorts of terrible side effects, but essentially none of them carry over to clinical amphetamine use (eg Adderall for ADHD). This is mostly because recreational users take doses orders of magnitude higher; “the dose makes the poison”.
In general, I’m not very concerned about this with most patients, for a few reasons. First are the reports from expert prescribers, who say basically none of their patients ever get addicted. Second is the general experience of using addictive drugs in psychiatry – for example, amphetamine (Adderall), which despite its fearsome reputation as a street drug is rarely abused by patients who get it by prescription. Addiction is a biopsychosocial process and people without genetic and psychological predispositions to addiction are usually able to use these chemicals safely.
In a survey of drug experts, ketamine was ranked as less addictive than tobacco, alcohol, or Adderall, and around the same level as marijuana. If you would feel comfortable going out to a bar a few times without worrying about addiction, or smoking pot a few times without worrying about addiction, probably you also shouldn’t worry about getting a few ketamine infusions.
July 21, 2021 · Original source
Living in Russia, I can say that ADHD (translated as СДВГ) is less recognized by the psychiatry community here because of its unclear aetiology. Doctors usually refuse to treat the patients in the absence of dangerous symptoms, and state the diagnosis as "organic nervous system disorder", "psychoorganic syndrome" or indeed "neurasthenia". Adderall and Ritalin are illegal drugs here. Patients usually get prescribed nootropics (glycine, racetams) and adrenaline reuptake inhibitors (atomoxetine).
At the same time there are some articles in popular online magazines telling stories about children and adults struggling with ADHD in Russia. Some people order illegal drugs from nearby countries. Researchers also are aware of it. At the same time, I see some articles talking about US problems with over-medicalization of ADHD with dangerous narcotics driven by profit-seeking pharma companies.
I would be surprised if ADHD was especially culture-bound. Partly this is because it’s much more genetic than most other conditions. But partly it’s because it’s just a really basic deficit. Some people aren’t very smart. Other people aren’t very coordinated. And still other people aren’t very good at concentration / executive function (see my past discussion of this here). There’s no reason why everyone should have the same level of concentration ability, so sure, some people have extremely bad concentration ability (just as some people are really dumb, or really clumsy), and we call that ADHD. This seems much less mysterious than “sometimes people can’t stop dieting and starve themselves to death”.
November 16, 2022 · Original source
Everyone wants “magic bullets” - drugs that can increase dopamine in one of these ways, but not any of the others. Treat attention problems without causing hallucinations. Cure tremors without causing hypersexuality. But it’s tough. There are dozens of dopamine-based drugs, and all of them succeed in some ways and fail in others. Adderall mostly helps attention but sometimes causes a little paranoia on the side. Antipsychotics mostly prevent hallucinations and delusions, but also cause anhedonia. If a good doctor carefully chooses the right drug and dose, you’ll mostly get what you want. Otherwise, choose 2d4 random side effects from the appropriate side of the table.
I don’t think Emsam is vastly worse than other dopaminergic drugs - maybe even including common drugs like Adderall. I think all of these drugs are fine for ordinary people who need antidepressants or stimulants. They might even potentially be fine for people who work with risk as a job, like traders - especially if they’re following an algorithm or having their work checked by other people. But if someone’s making big decisions based on their intuitive risk assessments, they should keep in mind that dopaminergic drugs can shift the way they think about those things - not necessarily to a worse place, just a different place.
A significant fraction of the finance industry is on Adderall - I know because they keep trying to make me prescribe it to them. This hasn’t degraded performance so much that managers have noticed or made rules against it. And for all I know, maybe the medicated mental risk curves are better for trading than the unmedicated ones. Still, I would warn everyone involved to be careful.
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
December 28, 2022 · Original source
10: Reason: Blame The Government For The Adderall Shortage. The DEA sets a cap on how much Adderall companies can produce per year, and maybe the current Adderall shortage is because they chose too low a number. “Despite the shortage, the DEA has indicated that it does not intend to raise the limit next year.” But the article is kind of equivocal about this and says supply chain problems might also be the culprit.
March 29, 2023 · Original source
The first fruit of their labor is DEA-407, which makes it hard for telemedicine doctors to prescribe controlled substances. Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien that the government has declared to be potentially addictive. The new rules say that telemedicine doctors can no longer prescribe these (or, in some cases, can prescribe them one time in an emergency).
Some like convenience and dislike inconvenience As a psychiatrist, a big part of my job is prescribing controlled substances. For example, most guidelines agrees that the first-line treatment for severe ADHD is stimulant medications (eg Adderall or Ritalin). And although psychiatrists hate to admit it, the first-line treatment for temporary crisis anxiety, especially when it’s so bad that the patient isn’t able to listen to your clever plans to solve it with therapy, is benzodiazepines (eg Valium or Klonopin). You can’t be a good well-rounded psychiatrist without the option to sometimes prescribe these drugs. "Well, your patients will have to find a different psychiatrist, or transition off of them”. Nobody ever finds different psychiatrists. Some of my patients are a bad match for my style or areas of expertise, and I’ve tried very hard to find them different psychiatrists, and it never works. Maybe there are no other psychiatrists in their area. Maybe the psychiatrists in their area don’t take the right insurance, or are too far away from mass transit. Maybe the psychiatrists have six month long wait lists. Sometimes it’s just that my ADHD patients get distracted and forget they were supposed to find new psychiatrists, and I can’t hold their hand literally all the time. As for transitioning off the medications, some patients absolutely cannot function at all without them. Did I mention that if you come off of some of them too quickly, you can literally die? The medical regulators grudgingly acknowledge these issues and have placed two loopholes in the law: If you ever see a doctor in person, even once, they can prescribe you controlled substances from then on, even if they only see you by telemedicine afterwards.
April 03, 2023 · Original source
Some people express concerns about “pill mills”, unscrupulous companies that hire doctors to prescribe to anyone who asks. These are pretty common for Adderall in particular. Michael:
There were some very dubious telemedicine psychiatry startups that would prescribe Adderall or Ritalin, seemed to have very low prescribing standards, and advertised very aggressively on social media. They were previously only doing SSRIs and the like, but moved to ADHD drugs when this became temporarily possible after COVID.
This is an overresponse to the adderall shortage. There was an uptick in prescriptions over the pandemic and this was blamed on Cerebral and the like. Judging by Cerebral's advertising, I'm not surprised they're being branded a pill-mill; they definitely look like one. I'm currently seeing a telemedicine psych for adhd because I couldn't find an in-person psych during the pandemic, but when I saw Cerebral's adds, I figured I should avoid them.
June 08, 2023 · Original source
Adderall helps ADHD: 1.3
December 06, 2023 · Original source
If we eliminate prescriptions, then how do you get Adderall and painkillers? Remember, the FDA doesn’t fight the War on Drugs - that’s the DEA, a different agency. Many recreational drugs (including dangerous ones like methamphetamine, cocaine, and fentanyl) have accepted medical uses. Right now, you’re allowed to use those drugs with a prescription, but not otherwise. If there’s no prescription system, can everyone buy these drugs at the corner store? Can nobody buy them?
May 29, 2024 · Original source
2: Recursive Adaptation: The Growing Scientific Case for Using Ozempic and other GLP-1s to Treat Opioid, Alcohol, and Nicotine Addiction. Early studies suggest that new-generation weight loss drugs like Ozempic treat all addictions. The next step is seeing if the government and insurances will cooperate with using them for that indication. As usual, the barrier is cost, but people seem committed enough to doing something about the opioid crisis that they might be willing to act. I think these drugs might boost willpower more generally. There might come a day when they get treated like Adderall - something that many ambitious people want to be on, and look for excuses to take.
36: Alex Tabarrok and New York magazine explain the Adderall shortage. Summary: the DEA, in its crusade against opioids, has put such strict standards on medication factories that many have gotten shut down for “trivial infractions” (for example, “orders struck from 222s must be crossed out with a line and the word cancel written next to them. Investigators found two instances in which Ascent employees had drawn the line but failed to write the word”). In this case, the FDA is the good guys trying to get the factories to re-open again, but so far the DEA hasn’t budged.
August 22, 2024 · Original source
I’m pretty encouraged by it. Not only does it provide GLP-1 drugs for a quarter of the price, but also people were really worried that diabetics wouldn’t be able to get their diabetes drugs because dieters would grab them off the shelf first. But now there’s more than enough GLP-1 agonists for everybody. This dramatically demonstrates how drug shortages are mostly regulatory problems (Adderall users, take note!)
November 01, 2024 · Original source
This was before they invented what we would call antidepressants today; Dexedrine is an amphetamine related to Adderall. 24: Congratulations to Open Philanthropy, the biggest effective altruist foundation… …whose grantee David Baker recently won a Nobel Prize for his research on synthetic proteins. Potential applications include new drugs, vaccines, and materials. 25: Rich Kid Memes And The Online Culture Of The One Percent. Rich people who want to signal group membership to other rich people online can’t boast about how rich they are; that would be gauche. Instead, they’ve settled on the solution of making fun of rich people in hyperspecific language that proves familiarity with the culture. 26: Tap Water Sommelier: Vladimir Putin has two sons, ages 5 and 9. They are kept in luxurious but total isolation from the outside world and raised by flunkies who are too scared to punish/restrain them in any way. Also some discussion of an unexpected historical analogue. 27: Experiment from Colombia: replacing experienced teachers with less-experience but higher-scoring-on-tests teachers significantly decreased student performance. Got to admit I was expecting the opposite of this, I’d seen US data saying that experience didn’t matter and teacher intelligence did. Looking over this more, I find lots of studies on both sides and will go back to agnosticism on this question until someone I trust investigates further. 28: Large scale-formal Intellectual Turing Test finds that people can imitate partisans effectively; ie nobody on either side can tell the difference between a Democrat arguing for Democrat values vs. a Republican-pretending-to-be-a-Democrat arguing for Democrat values (and vice versa). This study used a 100 word essay on why you supported your party (you can see if you can do better here), but past attempts with different structures (religion, vegetarianism, polyamory) have shown broadly the same results. The researchers try to put this in the context of various studies showing that people do misunderstand their opponents (eg think they’re more extreme, underestimate the level of common ground), but it seems like intellectual Turing Tests aren’t a good way to measure or tease out this misunderstanding. 29: Congratulations to Substacker WoolyAI for doing the impossible and providing a genuinely novel and interesting (to me) take on pickup artistry: 30: Did you know: if you Google “cool websites”, our subreddit (r/slatestarcodex) is the first result. 31: Moshe Koppel, who works at the intersection of computer science and Talmud, is writing a series of posts (presumably) based off of my Every Bay Area House Party, titled Jerusalem Area House Party (it’s multiple part, you have to go to the main Substack page to find the others). I won’t necessarily link everyone who riffs off one of my posts - but honestly I probably will if you also have a Wikipedia page that describes you as working on computational Talmudology. 32: David Roman says it’s a myth that Arabic scholars rescued and preserved the works of the great classical authors. 33: Medications often decrease “secondary endpoints” (eg stroke, heart attack), but the holy grail of pharma studies is proving that a certain drug decreases all-cause mortality. This is much harder (not all heart attacks kill people, and people die from lots of other things), but is the strongest possible endorsement for the drug (without it, you might worry that it only prevented non-fatal heart attacks, or that it killed as many people through side effects as it saves through heart attack prevention). Even great medications that we’re confident in can’t always clear this bar. But a new JAMA article adds another member to this select club: Adderall decreases all-cause mortality in ADHD, probably because it prevents drug addiction, car accidents, and impulsive actions. 34: Before the Gulf War got in the way, Saddam Hussein was building some crazy mosques: 35: Italy bans surrogacy - quite strictly, too, Italians aren’t even allowed to go abroad and do it. I am so sorry for all the Italians who will never get to be mothers and fathers because their government hates progress. You might hope that, whatever the other disadvantages of anti-immigrant parties, at least they’re incentivized to let natives have children, but looks like they can’t even get that one right. Starting to wonder whether the trains even run on time. 36: Elsewhere in “Italy sucks” news - did you know Italy’s tax code effectively bans startups? Companies are taxed before making any money, based on how many assets they have. If they have lots of assets but aren’t making money (eg because they’re still doing research / in stealth) then tax officials get confused and hostile and run increasingly punitive audits. Related: size of the European tech sector. It’s the red line on this chart; if you can’t see a red line at your screen resolution, then you’ve learned something important about the the EU tech sector. 37: Seen on @cremieuxrecuel’s twitter (preliminary, needs replication): Jews may have gone from 65-29 Democrat/Republican in 2020 to 58-40 this election. 38: Extelligence has a post responding to my critique of the cultural Christianity argument (among, uh, many other things), but I don’t really think it connects. I’m not telling atheists they can’t go to church/synagogue if it makes them feel happy and fulfilled - I’ve done this myself sometimes. My post was meant to argue against the claim that, for pragmatic reasons, atheists should support the Christianization of society as a defense against Islam or postmodernism or some other philosophical enemy. 39: Related: Extelligence is finally going for their Trust Assembly project/idea/startup for online consensus-based truth-seeking (I think something like a cross between Community Notes and Wikipedia, but as a browser extension, and for everything). He’s looking for potential developers/testers/users. 40: Jiankui He is the Chinese geneticist who made history with the first germline gene editing in humans (resulting in three babies supposedly immune to AIDS, although nobody has tested this). China sentenced him to three years in prison for unauthorized experimentation, but now he’s out of jail, has an English-language Twitter account, has a new lab, wants to work on Alzheimers, and seems pretty based (although not infinitely based): 41: Anthropic has a new version of their AI Claude which can use your computer. You give it permission, put it on a virtual desktop, and ask it to do things for you (eg “please find and download a picture of a cat” or “please research these ten things and put them in a text file”.) It moves your cursor, browses the Internet, and creates and saves files. People keep saying they’ll care about AI “when it operates autonomously” or “when it becomes an agent”. But this is a trivial barrier, and one which Computer Use Claude has arguably already passed. So far this feature is limited to developers (though anyone with computer knowledge can sign up for it) but I expect it to be the near future of consumer AI, to get better quickly, and to shade gradually into the “autonomous” “agentic” AI that you all think will require a paradigm shift. 42: Claim (from the IDF): Hamas faked polls showing that most Palestinians supported the October 7 attack; the real numbers are 31% in favor, 64% against. 43: Otto von Bismarck wanted to trick France into declaring war on Germany. In order to provoke the French, he sent the Ems Dispatch, a statement describing recent diplomatic events in a way that sounded maximally offensive. The French were so offended that “crowds” in Paris demanded war, and the Franco-Prussian War was declared soon afterwards. The part of this that I find most interesting is the text of the dispatch itself, which read: After the news of the renunciation of the Prince von Hohenzollern had been communicated to the Imperial French government by the Royal Spanish government, the French Ambassador in Ems made a further demand on His Majesty the King that he should authorize him to telegraph to Paris that His Majesty the King undertook for all time never again to give his assent should the Hohenzollerns once more take up their candidature. His Majesty the King thereupon refused to receive the Ambassador again and had the latter informed by the Adjutant of the day that His Majesty had no further communication to make to the Ambassador. I’m fascinated by the idea that only 150 years ago, it was obvious that if someone sent you this statement, you had to declare war or abandon all honor. If I read it carefully, I can sort of parse out that it sounds like the Prussians are unhappy, but that’s the most emotion I gather from it. Anyway, the Franco-Prussian War led to World War I which led to World War II - so if you don’t like 50 million people dying and the total devastation of Europe, blame this statement about ambassadors. 44: The first use of artificial insemination in humans: The first recorded case of artificial insemination by donor didn’t occur until 1884, when Dr. William Pancoast decided to treat a couple’s infertility by secretly inseminating the woman with sperm obtained from a medical student. The insemination happened while the patient was under anesthesia and Dr. Pancoast did not tell her what had occurred. She gave birth to a baby boy nine months later, but it was several years before the doctor finally confessed to her husband what he had done. Neither man ever informed the mother. It was 25 years later the result of this case was published. Dr. Pancoast was roundly condemned for his actions, but it did open the door for consensual sperm donor insemination. 45: ClearerThinking administers several personality tests to the same people to learn more about their comparative accuracy. I am most interested in their finding that tests with “factors” (eg the Big Five, where you rate people on a numeric scale) are inherently more accurate than those with “types” (eg Myers-Briggs, where you assign someone a specific category) and that, adjusting for this, Big Five is no more predictive than the Enneagram: 46: In 2022, I wrote Whither Tartaria, where I asked why ornate classical styles switched to more austere modernist styles around 1900 - 1950 in a variety of different arts (painting, architecture, literature, poetry, etc). I proposed seven theories, but was unsure which if any were true. Since then, Samuel Hughes of Works In Progress has been investigating. In May, he wrote a well-researched article showing that it wasn’t just increasing cost, because ornate classical architecture now costs less than ever. Now in a new article he demolishes a different theory - it’s not just decreasing cost (and subsequent lack of ability to signal wealth) - because costs didn’t decrease in several other arts, and the change was led by artists with rich people as reluctant followers. He concludes: Modernism may well be a status game of some kind; it may well signal taste more than it signals wealth; and this latter feature may be one of the things that distinguishes it from older artistic styles. But the mechanism by which this change came about must be different to the one Alexander describes. 47: Sort of kind of related - When Hamilton Lost Its Snob Appeal. The musical Hamilton was briefly an artistic/cultural phenomenon, but tastemakers eventually switched to making fun of it. Why? Rob Henderson says it happened after ticket prices came down and the common people could enjoy it. I disagree: everyone I knew who was into Hamilton got into it from the free online soundtrack long before they’d seen the show; I think this is more likely the usual fad cycle where anybody who’s too into yesterday’s fad is behind the curve and therefore uncool. 48: Related: Why are people such jerks to public intellectuals? And more. I agree this is a great mystery. 49: Some prominent Substack psychiatrists doing a video Q&A, submit your questions here. 50: Naomi Kanakia: The Literacy Delusion had a number of explanations for why reading books seemed to be so much worse for human beings (in terms of emotional wellness and productivity) than other forms of narrative entertainment, but its main theory was the integration hypothesis. That the stream of words in a book trained the human brain into a habit of self-consciousness, that reading books forced human beings to think of themselves as a stream of text, processed through time, making a coherent argument of some sort. And that this overall flattening effect forced readers to ignore aspects of their personality or their situation that were not otherwise in line with the overarching story they'd created about themselves. Basically, reading books causes repression and neurosis. The Literacy Delusion argued that, yes, human beings are storytelling machines, but that a stream of written text is a particular kind of story—a story that is particularly flat, particularly devoid of conflicting or harmonizing information—and that this flatness creates a peculiar effect on the human brain. 51: Last month, I linked Sasha Gusev’s No, Intelligence Is Not Like Height and asked people who disagreed to share their arguments; they sure did. First, several people pointed me to a new preprint, Family-GWAS Reveals Effects Of Environment And Mating On Genetic Associations, which finds that one of the main papers Gusev cited to make his case, Howe 2022, made a mistake - imputing sibling genotypes using a process designed for non-sibling genotypes - and that once that mistake is corrected, the finding disappears and intelligence and height appear similar. Second, Joseph Bronski has a more specific post where he responds to Gusev’s points one by one. He accuses Gusev of “[making] up his own chart to remove the error bars [from the originals], to obscure the fact that the study found no evidence for this in IQ”, and says that the cases where he didn’t do that are just “population stratification and range restriction”. Third, Noah Carl at Aporia, instead of writing a direct response like Bronski, argues that the usual method of attacking twin studies is obsolete; not only have the most-debated assumptions behind twin studies been thoroughly validated, but there are now other lines of evidence besides twin studies which confirm high IQ heritability. Fourth, Leonardo Parro (not framed as a response to Gusev) goes into more depth about one of those ways, a “pedigree-based analysis” demonstrating heritability of 54 - 69%, ie no “missing heritability” compared to twin studies. He summarizes this as the effect of “rare variants” compared to the usual SNPs - ie if you only look at the most common genes that are easiest to find, you get “missing heritability” compared to twin studies, but if you widen your search to rare genes that are hard to find, you don’t. 52: Extremely related: Heliospect is a startup promising polygenic selection for IQ and other traits; they were trying to stay in stealth mode but The Guardian spied on them and nonconsensually revealed their existence. The discussion on the r/ssc subreddit centered on their claim that (given enough embryos to choose from) they could increase a baby’s expected IQ by 6 points (I’ve also heard 7.5). Sasha Gusev had previously argued that current technology maxed out at 3.5 and future technology would max out at 6, so a claim of 6 - 7.5 is pretty extreme; Gwern, who wrote the pioneering analysis of this technology, was also skeptical. But Heliospect says they’ve got better predictors than academia that use the rare variants everyone else misses; after talking to the company, Gwern retracted his objections and says he finds their claim “pretty plausible”. Local ACX commenter geneticist Gene Smith also redid some calculations, changed his mind, and says “probably pretty realistic”. I find this interesting not just because of the polygenic selection angle, but because if Heliospect is right then their predictor is able to predict more genetic IQ than the “missing heritability” people believe exists, and it should be able to put this argument to bed once and for all. 53: This month in censorship: X/Twitter banned journalist Ken Klippenstein for sharing the Trump campaign’s dossier on JD Vance. Twitter’s side of the story is that the dossier was probably originally stolen by Iranian agents and they don’t want to support that kind of thing by letting people signal-boost the illicitly obtained goods; you can read Klippenstein’s side here. He appears to be unbanned now.
30: Did you know: if you Google “cool websites”, our subreddit (r/slatestarcodex) is the first result. 31: Moshe Koppel, who works at the intersection of computer science and Talmud, is writing a series of posts (presumably) based off of my Every Bay Area House Party, titled Jerusalem Area House Party (it’s multiple part, you have to go to the main Substack page to find the others). I won’t necessarily link everyone who riffs off one of my posts - but honestly I probably will if you also have a Wikipedia page that describes you as working on computational Talmudology. 32: David Roman says it’s a myth that Arabic scholars rescued and preserved the works of the great classical authors. 33: Medications often decrease “secondary endpoints” (eg stroke, heart attack), but the holy grail of pharma studies is proving that a certain drug decreases all-cause mortality. This is much harder (not all heart attacks kill people, and people die from lots of other things), but is the strongest possible endorsement for the drug (without it, you might worry that it only prevented non-fatal heart attacks, or that it killed as many people through side effects as it saves through heart attack prevention). Even great medications that we’re confident in can’t always clear this bar. But a new JAMA article adds another member to this select club: Adderall decreases all-cause mortality in ADHD, probably because it prevents drug addiction, car accidents, and impulsive actions. 34: Before the Gulf War got in the way, Saddam Hussein was building some crazy mosques: 35: Italy bans surrogacy - quite strictly, too, Italians aren’t even allowed to go abroad and do it. I am so sorry for all the Italians who will never get to be mothers and fathers because their government hates progress. You might hope that, whatever the other disadvantages of anti-immigrant parties, at least they’re incentivized to let natives have children, but looks like they can’t even get that one right. Starting to wonder whether the trains even run on time. 36: Elsewhere in “Italy sucks” news - did you know Italy’s tax code effectively bans startups? Companies are taxed before making any money, based on how many assets they have. If they have lots of assets but aren’t making money (eg because they’re still doing research / in stealth) then tax officials get confused and hostile and run increasingly punitive audits. Related: size of the European tech sector. It’s the red line on this chart; if you can’t see a red line at your screen resolution, then you’ve learned something important about the the EU tech sector. 37: Seen on @cremieuxrecuel’s twitter (preliminary, needs replication): Jews may have gone from 65-29 Democrat/Republican in 2020 to 58-40 this election. 38: Extelligence has a post responding to my critique of the cultural Christianity argument (among, uh, many other things), but I don’t really think it connects. I’m not telling atheists they can’t go to church/synagogue if it makes them feel happy and fulfilled - I’ve done this myself sometimes. My post was meant to argue against the claim that, for pragmatic reasons, atheists should support the Christianization of society as a defense against Islam or postmodernism or some other philosophical enemy. 39: Related: Extelligence is finally going for their Trust Assembly project/idea/startup for online consensus-based truth-seeking (I think something like a cross between Community Notes and Wikipedia, but as a browser extension, and for everything). He’s looking for potential developers/testers/users. 40: Jiankui He is the Chinese geneticist who made history with the first germline gene editing in humans (resulting in three babies supposedly immune to AIDS, although nobody has tested this). China sentenced him to three years in prison for unauthorized experimentation, but now he’s out of jail, has an English-language Twitter account, has a new lab, wants to work on Alzheimers, and seems pretty based (although not infinitely based): 41: Anthropic has a new version of their AI Claude which can use your computer. You give it permission, put it on a virtual desktop, and ask it to do things for you (eg “please find and download a picture of a cat” or “please research these ten things and put them in a text file”.) It moves your cursor, browses the Internet, and creates and saves files. People keep saying they’ll care about AI “when it operates autonomously” or “when it becomes an agent”. But this is a trivial barrier, and one which Computer Use Claude has arguably already passed. So far this feature is limited to developers (though anyone with computer knowledge can sign up for it) but I expect it to be the near future of consumer AI, to get better quickly, and to shade gradually into the “autonomous” “agentic” AI that you all think will require a paradigm shift. 42: Claim (from the IDF): Hamas faked polls showing that most Palestinians supported the October 7 attack; the real numbers are 31% in favor, 64% against. 43: Otto von Bismarck wanted to trick France into declaring war on Germany. In order to provoke the French, he sent the Ems Dispatch, a statement describing recent diplomatic events in a way that sounded maximally offensive. The French were so offended that “crowds” in Paris demanded war, and the Franco-Prussian War was declared soon afterwards. The part of this that I find most interesting is the text of the dispatch itself, which read: After the news of the renunciation of the Prince von Hohenzollern had been communicated to the Imperial French government by the Royal Spanish government, the French Ambassador in Ems made a further demand on His Majesty the King that he should authorize him to telegraph to Paris that His Majesty the King undertook for all time never again to give his assent should the Hohenzollerns once more take up their candidature. His Majesty the King thereupon refused to receive the Ambassador again and had the latter informed by the Adjutant of the day that His Majesty had no further communication to make to the Ambassador. I’m fascinated by the idea that only 150 years ago, it was obvious that if someone sent you this statement, you had to declare war or abandon all honor. If I read it carefully, I can sort of parse out that it sounds like the Prussians are unhappy, but that’s the most emotion I gather from it. Anyway, the Franco-Prussian War led to World War I which led to World War II - so if you don’t like 50 million people dying and the total devastation of Europe, blame this statement about ambassadors. 44: The first use of artificial insemination in humans: The first recorded case of artificial insemination by donor didn’t occur until 1884, when Dr. William Pancoast decided to treat a couple’s infertility by secretly inseminating the woman with sperm obtained from a medical student. The insemination happened while the patient was under anesthesia and Dr. Pancoast did not tell her what had occurred. She gave birth to a baby boy nine months later, but it was several years before the doctor finally confessed to her husband what he had done. Neither man ever informed the mother. It was 25 years later the result of this case was published. Dr. Pancoast was roundly condemned for his actions, but it did open the door for consensual sperm donor insemination. 45: ClearerThinking administers several personality tests to the same people to learn more about their comparative accuracy. I am most interested in their finding that tests with “factors” (eg the Big Five, where you rate people on a numeric scale) are inherently more accurate than those with “types” (eg Myers-Briggs, where you assign someone a specific category) and that, adjusting for this, Big Five is no more predictive than the Enneagram: 46: In 2022, I wrote Whither Tartaria, where I asked why ornate classical styles switched to more austere modernist styles around 1900 - 1950 in a variety of different arts (painting, architecture, literature, poetry, etc). I proposed seven theories, but was unsure which if any were true. Since then, Samuel Hughes of Works In Progress has been investigating. In May, he wrote a well-researched article showing that it wasn’t just increasing cost, because ornate classical architecture now costs less than ever. Now in a new article he demolishes a different theory - it’s not just decreasing cost (and subsequent lack of ability to signal wealth) - because costs didn’t decrease in several other arts, and the change was led by artists with rich people as reluctant followers. He concludes: Modernism may well be a status game of some kind; it may well signal taste more than it signals wealth; and this latter feature may be one of the things that distinguishes it from older artistic styles. But the mechanism by which this change came about must be different to the one Alexander describes. 47: Sort of kind of related - When Hamilton Lost Its Snob Appeal. The musical Hamilton was briefly an artistic/cultural phenomenon, but tastemakers eventually switched to making fun of it. Why? Rob Henderson says it happened after ticket prices came down and the common people could enjoy it. I disagree: everyone I knew who was into Hamilton got into it from the free online soundtrack long before they’d seen the show; I think this is more likely the usual fad cycle where anybody who’s too into yesterday’s fad is behind the curve and therefore uncool. 48: Related: Why are people such jerks to public intellectuals? And more. I agree this is a great mystery. 49: Some prominent Substack psychiatrists doing a video Q&A, submit your questions here. 50: Naomi Kanakia: The Literacy Delusion had a number of explanations for why reading books seemed to be so much worse for human beings (in terms of emotional wellness and productivity) than other forms of narrative entertainment, but its main theory was the integration hypothesis. That the stream of words in a book trained the human brain into a habit of self-consciousness, that reading books forced human beings to think of themselves as a stream of text, processed through time, making a coherent argument of some sort. And that this overall flattening effect forced readers to ignore aspects of their personality or their situation that were not otherwise in line with the overarching story they'd created about themselves. Basically, reading books causes repression and neurosis. The Literacy Delusion argued that, yes, human beings are storytelling machines, but that a stream of written text is a particular kind of story—a story that is particularly flat, particularly devoid of conflicting or harmonizing information—and that this flatness creates a peculiar effect on the human brain. 51: Last month, I linked Sasha Gusev’s No, Intelligence Is Not Like Height and asked people who disagreed to share their arguments; they sure did. First, several people pointed me to a new preprint, Family-GWAS Reveals Effects Of Environment And Mating On Genetic Associations, which finds that one of the main papers Gusev cited to make his case, Howe 2022, made a mistake - imputing sibling genotypes using a process designed for non-sibling genotypes - and that once that mistake is corrected, the finding disappears and intelligence and height appear similar. Second, Joseph Bronski has a more specific post where he responds to Gusev’s points one by one. He accuses Gusev of “[making] up his own chart to remove the error bars [from the originals], to obscure the fact that the study found no evidence for this in IQ”, and says that the cases where he didn’t do that are just “population stratification and range restriction”. Third, Noah Carl at Aporia, instead of writing a direct response like Bronski, argues that the usual method of attacking twin studies is obsolete; not only have the most-debated assumptions behind twin studies been thoroughly validated, but there are now other lines of evidence besides twin studies which confirm high IQ heritability. Fourth, Leonardo Parro (not framed as a response to Gusev) goes into more depth about one of those ways, a “pedigree-based analysis” demonstrating heritability of 54 - 69%, ie no “missing heritability” compared to twin studies. He summarizes this as the effect of “rare variants” compared to the usual SNPs - ie if you only look at the most common genes that are easiest to find, you get “missing heritability” compared to twin studies, but if you widen your search to rare genes that are hard to find, you don’t. 52: Extremely related: Heliospect is a startup promising polygenic selection for IQ and other traits; they were trying to stay in stealth mode but The Guardian spied on them and nonconsensually revealed their existence. The discussion on the r/ssc subreddit centered on their claim that (given enough embryos to choose from) they could increase a baby’s expected IQ by 6 points (I’ve also heard 7.5). Sasha Gusev had previously argued that current technology maxed out at 3.5 and future technology would max out at 6, so a claim of 6 - 7.5 is pretty extreme; Gwern, who wrote the pioneering analysis of this technology, was also skeptical. But Heliospect says they’ve got better predictors than academia that use the rare variants everyone else misses; after talking to the company, Gwern retracted his objections and says he finds their claim “pretty plausible”. Local ACX commenter geneticist Gene Smith also redid some calculations, changed his mind, and says “probably pretty realistic”. I find this interesting not just because of the polygenic selection angle, but because if Heliospect is right then their predictor is able to predict more genetic IQ than the “missing heritability” people believe exists, and it should be able to put this argument to bed once and for all. 53: This month in censorship: X/Twitter banned journalist Ken Klippenstein for sharing the Trump campaign’s dossier on JD Vance. Twitter’s side of the story is that the dossier was probably originally stolen by Iranian agents and they don’t want to support that kind of thing by letting people signal-boost the illicitly obtained goods; you can read Klippenstein’s side here. He appears to be unbanned now.
February 18, 2026 · Original source
Increased psychiatric care: all of the would-be criminals are on SSRIs, antipsychotics, and Adderall.
Apple

Apple is a recurring brand in the Astral Codex Ten archive, appearing 16 times across 16 issues between March 15, 2021 and January 21, 2026. The archive places it in contexts such as "Apple releases new iMacs powered by Apple silicon"; "Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores"; "Apple and Google both blocked Parler from their phones". It most often appears alongside Trump, Twitter, United States.

Article page
Apple
Mention count
16
Issue count
16
First seen
March 15, 2021
Last seen
January 21, 2026
March 15, 2021 · Original source
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races 2. The same party wins both Senate races in Georgia 3. Joe Biden ends the year with his approval rating higher than his disapproval rating 4. Joe Biden ends the year with his approval rating above 50% 5. US GDP growth in 2021 is the fastest of any year of the 21st century 6. The year-end unemployment rate is below 5 percent 7. The year-end unemployment rate is above 4 percent 8. Lakers win the NBA championship 9. Joe Biden ends the year as president 10. Nancy Pelosi sets a definitive retirement schedule 11. A vacancy arises on the Supreme Court 12. The EU ends the year with more confirmed Covid-19 deaths than the US 13. Substack will still be around 14. People will still be writing takes asking if Substack is really sustainable 15. Apple releases new iMacs powered by Apple silicon 16. Apple does not release a new Mac Pro powered by Apple silicon 17. Monthly year-on-year core CPI growth does not go above 2 percent 18. Monthly year-on-year core CPI growth does not go above 3 percent 19. Lloyd Austin not confirmed as Defense Secretary 20. No federal tax increases are enacted 21. Biden administration unilaterally relieves some but not all student debt 22. United States rejoins JCPOA and Iran resumes compliance 23. Israel and Saudi Arabia establish official diplomatic relations 24. US and China reach agreement to lift Trump-era tariffs 25. Slow Boring will exceed 10,000 paid members
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races (60%) 2. The same party wins both Senate races in Georgia (95%) 3. Joe Biden ends the year with his approval rating higher than his disapproval rating (70%) [83%] 4. Joe Biden ends the year with his approval rating above 50% (60%) [60%] 5. US GDP growth in 2021 is the fastest of any year of the 21st century (80%) [84%] 6. The year-end unemployment rate is below 5 percent (80%) 7. The year-end unemployment rate is above 4 percent (80%) 8. Lakers win the NBA championship (25%) [25%] 9. Joe Biden ends the year as president (95%) [96%] 10. Nancy Pelosi sets a definitive retirement schedule (60%) 11. A vacancy arises on the Supreme Court (70%) [50%] 12. The EU ends the year with more confirmed Covid-19 deaths than the US (60%) [80%] 13. Substack will still be around (95%) 14. People will still be writing takes asking if Substack is really sustainable (80%) 15. Apple releases new iMacs powered by Apple silicon (90%) [84%] 16. Apple does not release a new Mac Pro powered by Apple silicon (70%) [53%] 17. Monthly year-on-year core CPI growth does not go above 2 percent (70%) 18. Monthly year-on-year core CPI growth does not go above 3 percent (90%) 19. Lloyd Austin not confirmed as Defense Secretary (60%) 20. No federal tax increases are enacted (95%) 21. Biden administration unilaterally relieves some but not all student debt (80%) 22. United States rejoins JCPOA and Iran resumes compliance (80%) 23. Israel and Saudi Arabia establish official diplomatic relations (70%) [38%] 24. US and China reach agreement to lift Trump-era tariffs (70%) 25. Slow Boring will exceed 10,000 paid members (70%) [75%]
What you really want is to have everyone answering the same questions. But that's not really what punditry is about. I don't even know what an "Apple Silicon" is, I don't claim to understand it, and my work as a blogger doesn't involve making any predictions about it. I will fail all questions that involve pontificating on "Apple Silicon", and that's fine. But that means you can't ask me and Matt Yglesias to answer the same set of questions to decide which of us is a "better pundit". In fact, you don't want to do this - part of being a good pundit is knowing what your areas of expertise are, and limiting yourself to them.
March 25, 2021 · Original source
Earlier this year, Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores. A lot of libertarians objected that it was pretty scary that corporations have so much power to restrict speech they don't like, and a lot of anti-libertarians made fun of them: this is just corporations making their own decisions about their corporate property! Isn't that what you libertarians want?
But other fields have higher entry barriers than cars do. Apple and Google both blocked Parler from their phones. But these are the only two major smartphone companies. It would probably take at least a decade to set up another one, and although I think there's some demand, I'm not sure that demand can coordinate itself into a phone company that doesn't do this kind of thing.
April 19, 2021 · Original source
For a dose of cold water, see Investing in Technological Revolutions by Ben Felix. Remember, it's not how much a sector grows that makes it a good investment so much as how much it grows relative to what you paid for it. The highest return on investment stock of all time hasn't been Google, or Apple, or Tesla, or any other tech company you can name. It's Altria (MO) the cigarette company - annual returns have averaged 20.68% for nearly 50 years. Over half a century of innovation, hype, the Space Race, hype, the IT Revolution, and hype, the best returning company was in an industry everyone knew was on its way out (tobacco) - but which was on its way out far slower than everyone expected. That meant while everyone was dumping it, you could pick up the stock for peanuts relative to how much money the company was still making, and collect decades of dividends when the money flow didn't dry up.
August 12, 2021 · Original source
In this model, we end up with Woke Capital because Apple and Amazon are run by programmers, by managers who used to be programmers, and by MBA finance people - and all of those groups are highly educated and therefore liberal. In the past it might have also mattered that Apple and Amazon are run by rich people, but in the US that's stopped predicting anything.
January 07, 2022 · Original source
My movie-watching group debated who Tech CEO (Peter Isherwell) was based off of. Most of us thought Elon Musk, given his space adventures. But Urwin on ACX Discord proposes a dark horse candidate: Apple VP Craig Federighi. Side by side:
May 04, 2022 · Original source
This is weird, because the old Slate Star Codex layout was - mostly something I threw together in a day or two. I am widely recognized as not having taste, and the only website I ever developed before this was a Geocities site that was even worse. A few of my web designer friends helpfully smoothed over some rough edges (in one case literally, Apple-style), but the basic design remained my amateurish rush job.
August 26, 2022 · Original source
The general idea is that “A poem can be made of anything”. This is simply because any discreet word possesses many possible meanings. First, the immediate, direct, as in the word Apple means a type of fruit to anyone who speaks English. And then the internal, indirect: Apple means Sin or Temptation or New York or the color Red or the color Green or a Record Company or a Tech Company or all of that at the same time and more depending on the specific conjunction of reader and writer, and that internal meaning is, according to Wassily Kandinsky, “the pure matter of poetry and literature, the material which these arts alone can manipulate and through which they speak to the spirit”
September 22, 2022 · Original source
That's the part Scott and so many others miss. It isn't "lone genius has a clever idea, hires a bunch of people to Make It So under his management, and collects his billions". It's an iterative process, with each step increasing revenues, increasing costs, and increasing benefits. The no-billionaires version means SpaceX exists, but it never built anything bigger than the Falcon 5. Tesla exists, and produces a few thousand Roadsters a year. Amazon exists, and sells books. Apple exists, and sells Macintosh desktop computers.
February 20, 2023 · Original source
Some big macroeconomic indicator (eg GDP, unemployment, inflation) shows a visible bump or dip as a direct effect of AI (“direct effect” excludes eg an AI-designed pandemic killing people) : 15% LIMITS OF SCALING: In theory, GPT-4 will bump up against some fundamental limits of scaling (eg it will use all text ever written as efficiently as possible in its training corpus). I've heard various claims about easy ways to get around this, which will probably work; I expect scaling to continue to produce gains, but this is less obvious than it's been the past five years. Training GPT-4 will cost $100M, which is a lot. Apple spends $20 billion per year on R&D, so it's not like tech companies can't spend more money if they want to, but after the next two OOMs it will start being bet-the-company money even for large actors. I still think it will probably happen, but all of these things might be hiccups that slow things down a little, maybe? The leading big tech company (eg Google/Apple/Meta) is (clearly ahead of/approximately caught up to/clearly still behind) the leading AI-only company (DeepMind/OpenAI/Anthropic) in the quality of their AI products: (25%/50%/25%)
The leading big tech company (eg Google/Apple/Meta) is (clearly ahead of/approximately caught up to/clearly still behind) the leading AI-only company (DeepMind/OpenAI/Anthropic) in the quality of their AI products: (25%/50%/25%)
May 26, 2023 · Original source
The act of using funds from the Piggly Wiggly Stores Inc bank account to buy shares in Piggly Wiggly Stores Inc. sounds a lot like a "buyback" (something which companies do from time to time; Apple seems to be a particular fan of the practice having done it most recently in 2022), but nowadays the SEC has strict rules about when and how buybacks can be executed, and many aspects of buybacks as we understand them today weren't formalized until the 1980's.
July 21, 2023 · Original source
We need a framework for thinking about these trades. Lebron’s first law states that we must know ourselves and our motivations for trading before we trade. We tell ourselves many stories, but someone with intellectual honesty – the person with the most alignment between their motivations and actions – will take money from the person who didn’t go through the work to understand their own motivations. There is a reason that Citadel and other hedge funds pay millions of dollars to trade with retail. They know why they are trading: to maximize profit. And the dilettante who “trades for fun” will be eaten alive by a firm with a much better model of a) the world and b) the dilettante themself. Why did I write this book review? To test my intellectual mettle. I could easily have posted this book review elsewhere, but no, I wanted to see how I stack up against other ACX Book Review contest participants. Similarly, this is often the reason people get into trading. One motivation that Lebron explicitly calls out is intellectual validation. You can toil in obscurity for years as an academic. But in trading, there is a quick feedback loop. If your P&L showed $10M last year and the guy sitting next to you showed $8M, you have demonstrated who is “cleverer” and established a clear hierarchy. What lessons here transfer to our daily lives? Like Paul Graham, Lebron encourages us to keep our identities small. He gives the standard decision-making advice to write down your framework and reasoning for why you made a decision at a specific point in time, in order to avoid biases after the fact. This section of the book contained good general advice, but nothing that will be particularly new for the median ACX reader. 2: Adverse Selection You’re never happy with the amount you traded. Now we start to get into the good stuff. Financial markets are an information aggregation mechanism, relying on multiple parties’ beliefs and recursive Bayesian updates of an individual actor’s beliefs based on the beliefs of others2. Market mechanics demonstrate Bayesian beliefs in action. The following quote is quite long, so skip over it if you don’t want to dive deep into the psychology of making a market. I retained it in full because this is quite literally the best description I’ve ever seen of the Bayesian dance between two market makers: “You are a market maker in South African mining companies. Through years of effort and continual improvement, you have built a trading model for the company Veldt Resources. You walk into work one day, ready to set up your trading for the day. It's a stock that doesn't trade much, and usually there are only two market makers: you and another (we'll call her Jo). She's sharp, and she competes well to trade against customer orders that come in. Your model has Veldt valued at 54.35 ZAR (South African rand). You're going to start quoting the stock, so you're about to turn on your machine making a market 54.25 - 54.45 (1000x)3. Before you turn on, you check the current market and notice that Jo has already turned on and she's making her market 53.50 - 54.00 (2000x). If you were to turn on your machine, your market would cross her market, and you would buy 1000 shares from her for 54.00. You now need to make a decision. Whose model do you believe more, yours or Jo's? If you believe yours, you should turn on your machine, trade at 54.00, and expect to make money. If you believe Jo's model, you should adjust your own model parameters to match her market and turn on, making a similar market to hers. What to do? As with many dichotomies, this is a false one. And as with many decision processes, Bayesian reasoning lights the way… …Jo presumably believes Veldt is worth around 53.75 (the average of her bid and offer). But how confident is she in her belief? The width of her market can give you a clue. It's 0.50 ZAR, whereas yours was going to be 0.20 ZAR wide. All other things equal, you should think that Jo only has 40% (0.20/0.50) of the confidence in her fair value as you do in yours. On some absolute scale of confidence, you can say you had a belief-strength of 100 in your fair value of 54.35 (before seeing Jo's market), and Jo has a belief-strength of 40 in her fair value of 53.75 (before seeing yours). And it turns out the weighted average of these two beliefs is quite a reasonable way to combine them: 100/140 * 54.35 + 40/140 * 53.75 = 54.18. Your updated fair value, having seen Jo's market, is thus 54.18 ZAR. This procedure is a quick, heuristic, and reduced version of Bayesian belief-updating, and a good reference on the subject is A.L. Barker's 1995 paper. After updating, you now believe that the stock is worth 54.18. Assuming your trading costs, risk limits, and return requirements are satisfied, buying 1000 shares for 54.00 is a good trade. Naively, you might just put out a 54.00 bid for 1000 shares, trade with half the 2000 share offer, and hope to collect your expected-value ZAR. In practice, however, you might be able to make even more. If Jo is making a 0.50 wide market, maybe she'd be willing to sell lower than 54.00. It's conceivable that if you put out a 53.90 bid for 1000 shares, Jo will sell at that price, and you collect an extra 100 ZAR! Of course, Jo could react differently. She could see your bid and use that information to change her market, in much the same way you did before turning on. These are difficult decisions, ones where experience with the product and the market make a big difference in being able to eke out a little extra edge. Let's play it safe however and pay 54.00 for 1000 shares. You trade, and Jo reacts by immediately canceling her market. This is not an uncommon occurrence in illiquid stocks, especially in emerging markets, so you're not too surprised. You wait a couple of minutes, mentally visualizing Jo in front of her six monitors, evaluating her trade and her model. Finally, she turns back on. Her new market is 53.50 - 54.05 (10000x)! You reason that Jo has seen that someone (you) disagrees with her valuation of the stock. Jo is a good Bayesian like you, and so she has incorporated that information into her model and updated her beliefs about the fair value of the stock. Her updated belief is that she now wants to sell even more stock, at a marginally higher price. Clearly, she almost entirely discounts the information you've communicated to her with your trade. How should you react? It seems fairly clear that, assuming Jo is not a crazy or incompetent market maker (usually a fair assumption), your trade was a bad one. You bought 1000 shares, when in retrospect, you would have wanted to buy much less, probably zero. Imagine instead that Jo had turned back on with a market of 54.00 - 54.50 (1000x). Her reaction now clearly indicates the information you gave her with your trade is valuable, and she has adjusted her beliefs accordingly. Your trade was probably a good one. Don't you wish you had bought all 2000 shares on offer? No matter what Jo's reaction is, you will be unhappy with your trade. Note that Jo will be unhappy too, since retrospectively she should have either made her initial market bigger or smaller. Welcome to the joyous world of trading!” Whether or not you make money, you have regrets! If you profited, you could have made more. If you lost money, you shouldn’t have made the trade at all. Like death and taxes, you can’t avoid adverse selection. Lebron continues to highlight a few areas of trading that have adverse selection problems. First, IPOs. If you buy the stock in an IPO, you expect the share price to “pop” on the first day of trading. However, if others also have this expectation, the round will be oversubscribed. You can only get the quantity of shares that you bid for when the market doesn’t think the shares will go up. So if you are able to get the shares that you want, the IPO is likely a dud. See also: Venture Capital fundraising. Second, powerful entities that change the rules of the game while you’re playing. Exchanges nullify “erroneous” trades. Brokerages limit buying. Anyone who tried to buy GameStop stock on Robinhood on January 28, 2021, knows this form of adverse selection all too well. Lebron also highlights “special trades”, in which you should throw the “normal rules” out of the window. This advice generalizes to other areas of life: “The normal rules do not apply. If you remove yourself from our usual routine, if you think hard and clearly about the specific situation, maybe you can do something good. Perhaps even great. Others will be paralyzed by inaction, but perhaps you won’t be. Crises can be opportunities.” 3: Risk Take only the risks you’re being paid to take. Hedge the others. In trading, as in life, you can make the right call in expected value terms but still lose due to randomness. Some of that randomness is avoidable. Some of it is not — and can be accounted for by hedging. Here, Lebron encourages us to rely on multiple risk measures and actively seek to understand the risks that we might be subject to. That’s all well and good in the world of finance, with derivatives contracts. But how might this apply in other areas of life? If you work for a publicly traded company and are compensated in stock, sell your shares as soon as you receive them. This is not because I don’t expect the share price of Microsoft/Meta/Apple/etc. to go up. The stock may very well outperform the market. But you are not being compensated for the added risk that you take on here. Your employment prospects at Microsoft/Meta/Apple/etc. are highly correlated with the share price. When the share price is down is when layoffs happen. Former Enron employees can chime in here. Similarly, it makes sense to hedge anything that is outside of your control. Let’s say you’ve decided the crypto bear market of 2023 is a great time to start a new crypto company. Your success depends on things within your control, such as: Your idea
“Residential real estate has historically returned significantly below equity markets over long time horizons” But I’m not so sure that these lessons are directly applicable to other areas of life. Some of the best things in life come from lashing yourself to the mast, burning the boats behind you, willingly giving up liquidity. The deepest monogamous relationships are built from an irrational investment in one other person, saying “In sickness and in health, until death do us part.” How many scientific problems were solved because one person had an irrational willingness to: Just. Keep. Going. Sometimes it’s powerful to use the sunk cost fallacy to your advantage. Investing in relationships, subject matter expertise, even putting down roots via *gulp* homeownership reduces your liquidity, but also leads to some of the best (if intangible) things in life. 5: Edge If you can’t explain your edge in five minutes, you don’t have a very good one. OR The long-term profitability of an edge is inversely proportional to how long it takes to explain it. The Efficient Market Hypothesis is one of the core concepts taught in Finance 101. The Efficient Market Hypothesis is a lie. The person that better understands the nature of a small sliver of the world (e.g. Apple’s share price) will make more money than others. Modern financial markets are exceedingly competitive. This means that the bigger you think your edge is, the more likely it is that you’re wrong. “Evolutionary thinking applies quite directly when thinking about the evolution of markets. Having an edge in a mature market means understanding the world better than other traders, even ones who are already highly skilled. In fact, the marginal trader in modern financial markets is quite sophisticated and skilled indeed.” Lebron here warns us of getting too cute with data, of changing variables. Enough randomness will produce an “edge” that is likely to break down the second a trading strategy hits the real world. You can always find a statistical correlation if you change enough variables. But this is fundamentally the same problem facing the replication crisis in social sciences. Lebron argues that we need stories here. Edge is expressed in stories: an edge does not exist without a clear mental representation of that edge. Pure linear algebra does not suffice. I’m not so sure. It seems like AI companies are pushing forward technology in a way that suggests that mental representations are not the only path to intelligence. Lebron discounts “black box” trading strategies without much discussion of their potential merits. Are all of RenTech’s models explainable by a story? The firm is notoriously secretive, so I don’t know, but I’d guess not. “Frequently a good trade appears, has a seemingly insurmountable difficulty, and it is mere persistence that knocks down the final barrier. There may have been many others who looked at the idea, wanted to do it, but couldn’t get past that last hurdle.” Before Sam Bankman-Fried was the face of Why Effective Altruism is Bad, before he even founded FTX, he made money arbitraging the difference between Bitcoin prices on Japanese and American exchanges. I’m reminded of that trade here. It isn’t a particularly elegant trade, it doesn’t require deep technical knowledge or any models. It was a schlep. It was all operational work: figuring out how to open a Japanese bank account, transferring money between the US and Japan, standing in line for hours every day at both US and Japanese banks (presumably this wasn’t the same person). In as technical a field as trading, sheer willpower is often what gets things done in the end. 6: Models The model expresses the edge. Lebron drills into us that a model is the tool for expressing an edge. The model is not the edge. The model does not give us unique knowledge about the world. The map is not the territory. He dives into the difference between generative (G) and phenomenological (P) models. G models express a worldview and fit data into that way of thinking, whereas P models solely look at the empirical data to build a worldview. Models of the world differ from models of markets, though. Markets have quick feedback loops, are explicit in terms of what they measure, and are easy to quantify at a specific point in time. Most of our models for the world, though, are ill-defined and explicit. Models are only as good as our assumptions. As an aside, this is a common criticism of rationality or Effective Altruism – you can justify any worldview if you assign your model input weights in just the right way5. I also tend to think that “traditional” EA is overly dependent on P models, and doesn’t embrace the G models that led to economic reforms in India in the 1990s or the economic policies that led to rapid economic development in Southeast Asia in the second half of the 20th Century. Interestingly, I think a lot of longtermist EA, specifically AI alignment, leans the other way, relying on G models which explicitly assume a certain P(doom) and work backwards from there. (Though I won’t pretend to be an expert here or to understand everything, so take this with a grain of salt.) Overall, startups and tech seem to take heed to Lebron’s lesson much better than the folks hanging out on this part of the internet: “Even if a model makes good predictions about some future value or event, that knowledge is useless without also knowing how to take advantage of that prediction.” Now we get a bit philosophical. By acting, you change the nature of the market. Your model predicts things that might not be true as soon as you start trading (and changing the environment) based on it. When you’re right, everyone else sees the same trades that your model does and will beat you to them. When your model is wrong, others don’t act, meaning adverse selection rears its ugly head once again. So your model shows you with an edge, but in practice you only make the trades where you don’t have an edge. Lebron closes by arguing that G models are best for understanding other people, and are good in and of themselves: “You can also see connections to traditional moral philosophy in thinking about modeling the behavior of others. To have a good G model about someone else is to have some measure of empathy and compassion for that person: what they’re like, what they think and feel, putting yourself in their shoes. Pragmatically, developing the skill of empathy and compassion for others is, aside from a moral good in itself, an excellent way to understand better the people who surround you. More people working to develop good G models of others is surely a small step to a better world.” 7: Costs and Capacity If you think your costs are negligible relative to your edge, you’re wrong about at least one of them. This section of the book displayed a good amount of epistemic humility, words that I didn’t expect to be typing in the context of a book about trading. Lebron tells us that trades don’t exist independently in the universe — in the n-dimensional space of all possible trades seeking to optimize profitability, if you have a gigantic mountain of profitability, someone else has probably at least discovered the base. So you probably don’t have a profitable trade; rather, you are misunderstanding something about your trade. You’ve either overestimated profitability or underestimated cost. Lebron highlights four types of trading costs: [graph that didn’t show up correctly here: two axes and four quadrants, with the axes being visible ←→ invisible costs and linear ←→ nonlinear costs] Here, we’ll focus on Quadrant 4, where he highlights a few interesting phenomena. Herding. It’s likely that if you have a profitable trading strategy, either: Other firms discovered a similar strategy independently and/or
January 10, 2024 · Original source
Amorites taking over Babylon: Okay, but the Babylonians could hardly go into the hills to wipe them out, so they got basically unlimited chances. The way I would frame this is that settled decadent people do win more often than they lose, but unsettled barbarians still seem to punch above their weight given the material disadvantages they face. In one of his few concessions to the Fremen, Devereaux has a soft spot for Ibn Khaldun’s theory of asabiyyah - that small tribes can maintain camaraderie and a “family” type atmosphere as their larger neighbors spread themselves too wide and get involved in satrapial backstabbing. The tightly-knit small tribe can then conquer the large but fragmented empire, benefit from its camaraderie for a generation or two until it fades away, and then become the next fragmented decadent empire in turn. Xenophon hints at this in Cyropaedia. Cyrus and his childhood friends form a tightly-knit cadre for the Persian army; their bonds of trust are unbreakable. Meanwhile, Assyria and all the Persians’ other enemies are collections of backstabbing vassals held together with gum and duct tape, who fragment at a mere poke from the crystalline perfection of the Persian machinery. In one of his few other concessions, Devereaux agrees that the Mongols were very impressive, but says this was because of very specific aspects of their society rather than general Fremenness. For example: Steppe warriors battled with tactics learned from the hunt and engaged in operations with logistics they used for every day survival. But it isn’t the ‘hardness’ of this way of life that provided the military advantage (if it was, one might expect non-horse cultures on similarly marginal lands to be equally militarily effective and – as we’ve shown – they were not), it was the overlap of very specific skills (namely riding, horse archery and the logistics of steppe pastoralism) that led to the military advantage. Okay, but one of Xenophon’s points is that Cyrus was a great warrior because he and his friends learned tactics from hunting constantly, and their foil the Medes didn’t do this because they were too civilized and decadent. So my model of Xenophon’s response to Devereaux would be that Devereaux is accurately recognizing various features of non-decadent societies, and judging each of them a contingent exception, rather than Directly The True Effect Of Non-Decadence. But non-decadence, if it’s valuable as a concept at all, will be made of things like “camaraderie among tribe members” and “a tradition of learning tactics from hunting”. Is it useful to think of all of these things as coming from a central concept of “non-decadence” rather than as a bunch of separate things? Here I think about Zvi’s review of Moral Mazes, a book about (essentially) corporate decadence, the difference between a bloated megacorporation and a nimble startup. On average, a bloated megacorporation beats a startup - the next-generation smartphone is more likely to be developed by Apple than by three people in a garage. But everyone agrees startups have advantages of their own, and are sometimes able to beat the megacorporation despite how unlikely this seems. Moral Mazes posits that the bloated megacorporation has so many layers of middle management that the average leader is dealing entirely with social reality - trying to manipulate the beliefs of other middle managers, who are themselves concerned mostly with the beliefs of other middle managers, and so on. Meanwhile, the startup is concerned mostly with physical reality. Either you’re working on real business things (like engineering the product, or looking for customers, or even managing the budget) or you’re at least managing someone who’s doing those things rather than living entirely in some giant house of mirrors. Megacorporations have high volume and low surface area - most points are far away from any boundary with the outside. Startups have low volume and high surface area - most parts of them are being constantly tested against reality and honed into some useful form. One reading of Cyropaedia portrays Cyrus the Great as a guy in touch with physical reality. Part of that is that he goes hunting (and later, goes into battle). But part of that is that his friends are real people, who are his friends for specific reasons, and not ten layers of courtiers and flatterers and vassals. Cultures whose leaders spend time in physical reality tend to get different norms from cultures whose leaders spend time in social reality (read Zvi if you don’t believe me). I think this is enough to link Ibn Khaldun, Xenophon, and the Western tradition of decadence (this is just a possibility proof, not an “I’m definitely right” argument). Then you could use that to explain why barbarians seem to punch above their weight (eg rule China 20% of the time even with 1% of the population). Did Cyrus The Great Invent Niceness? This is a claim I’ve sometimes heard. Machiavelli said that it is better to be both loved and feared, but if you can only have one, be feared. The history of the late Bronze and early Iron Ages is a history of fearmaxxing. Kings would torture their rivals and slaughter their enemies, then erect steles saying “I massacred the Vorgundians, laid waste the land of the Hapidians, enslaved the Gargulians . . . “ etc etc etc. The story goes that Cyrus was the first to get Machiavelli’s perfect balance of fear and love. I don’t know how true it is - some of this comes from the Cyrus Cylinder, Cyrus’ own propaganda about himself. Still, it has to mean something that when every other king erected steles about how many people he massacred or enslaved, Cyrus chose to write about how many people he had liberated, helped, or given rights back to. Wikipedia says: A comparison of the Cyrus Cylinder with the inscriptions of previous conquerors of Babylon highlights this sharply. For instance, when Sennacherib, king of Assyria (705-681 BC) captured the city in 690 BC after a 15-month siege, Babylon endured a dreadful destruction and massacre. Sennacharib describes how, having captured the King of Babylon, he had him tied up in the middle of the city like a pig. Then he describes how he destroyed Babylon, and filled the city with corpses, looted its wealth, broke its gods, burned and destroyed its houses down to foundations, demolished its walls and temples and dumped them in the canals. This is in stark contrast to Cyrus the Great and the Cyrus Cylinder. Sounds pretty easy to get a reputation as “the nice tolerant guy” when this is your competition! Xenophon follows the Cylinder and the invented-niceness side of the story. In fact, he hits you over the head with stories of how Cyrus was nice to people and it ended out helping him. For example: When the Armenians rebel against their master the Medes, the Medes send Cyrus to pacify them. Cyrus wins, but the Prince of Armenia argues that Cyrus should spare the life of his father the king, because this will be so over-the-top unexpectedly nice that his father will be a more grateful and helpful vassal than anyone else Cyrus could put in his place. Cyrus agrees and the Armenians are loyal to him forever.
May 29, 2024 · Original source
14: Related: Bentham’s Bulldog has been going over some of the evidence for Christianity, of which the most interesting is the story of St. Joseph of Cupertino (no, he didn’t work for Apple; it’s also a town in Italy - the Cupertino in California is named after him). Apparently St. Joseph could levitate, this was well-documented by everyone he met, and the Inquisition (which was concerned he might be a witch) investigated and got many eyewitness reports. Wikipedia has a more skeptical take, but I’m more interested in how well the Christianity hypothesis predicts this “evidence”.
February 27, 2025 · Original source
29: I’ve appreciated some of Jeff Mauer’s posts recently, especially Should People Who Blast Their Music In Public Receive Fines, Or Be Slowly Tortured To Death? (though recently I heard a claim that this is all downstream of Apple removing the headphone jack from their phone; I think government should intervene by fining the blasters, but if not pressuring Apple to add it back on externality grounds would be an interesting move) and Democrats Could Build A Message Around Competence If We Didn’t Have DEI Stink On Us (paywall).
May 07, 2025 · Original source
A patchwork of city-states, unbound by modern “international law”, with few barriers to the free flow of capital and population. I’ll then describe how carefully Moldbug explained that you had to have these things, or else the dictatorship would fail in more or less the ways normies expect dictatorships to fail - leaving himself no room for the kind of pivot he’s trying now. 1: Classic Moldbug Believed Populist Dictatorship Would End In Disaster Classic Moldbug admitted that fascism and communism were extremely bad. He just drew different borders around political systems: fascism, communism, third world banana republic dictatorship, and democracy all cluster together as systems where coalitions rule because they can seize temporary power in a semi-lawless society. In the various totalitarianisms, it’s literal seizing of power through armed troops or secret police; in democracy, it’s electoral seizing of power through distributing the most goodies to coalition members. From here, my bolding. Clearly, the worst forms of demotism, the really bad apes, were the totalitarian systems—fascism and communism. The main difference between fascism and communism was not in mechanism, but in origin—fascist elites tended to be militarist, communist elites intellectual. But the one-party state is a clear case of convergent evolution. To a neocameralist, totalitarianism is democracy in its full-blown, most malignant form. Democracy doesn’t always deteriorate into totalitarianism, and lighting up at the gas pump doesn’t always engulf you in a ball of fire. Many people with cancer live a long time or die of something else instead. This doesn’t mean you should smoke half of Virginia before lunch. A political party is a political party. It is a large group of people allied for the purpose of seizing and wielding power. If it does not choose to arm its followers, this is only because it finds unarmed followers more useful than armed ones. If it chooses less effective strategies out of moral compunction, it will be outcompeted by some less-principled party. When one party gains full control over the state, it gains a massive revenue stream that it can divert entirely to its supporters. The result is a classic informal management structure, whose workings should be clear to anyone who watched a few episodes of The Sopranos. Without a formal ownership structure, in which the entire profit of the whole enterprise is collected and distributed centrally, money and other goodies leak from every pore. Totalitarian states are gangster states, in other words, and they tend to corruption and mismanagement. The personality cult of dictatorship is quite misleading—a totalitarian dictator has little in common with a neocameralist CEO, or even a cameralist monarch. The difference is the management structure. The CEO and the monarch owe their positions to a law which all can obey, and those who choose to obey the law are naturally a winning coalition against those who choose to break it. The dictator’s position is the result of his primacy in a pyramid of criminals. This structure is naturally unstable. There is always some other gangster who wants your job. Dictators, like Mafia chiefs, are not good at dying in bed. The internal and external violence typical of totalitarian states is best explained, I think, by this built-in mismanagement. Dictators are violent because they have to be—they use violence as an organizing principle. The totalitarian state has no principle of legitimacy that would render it impractical for an ambitious subordinate to capture the state with a coup. European monarchs made war, sometimes they were assassinated, and there were even succession struggles, but coups in the modern sense were very rare. Note that the financial logic which keeps the neocameralist state lawful does not apply in any way to the totalitarian state, because the latter does not have a stable management structure which is controlled by its shareholders. Lawlessness is not profitable for the state as a whole, but it may be quite profitable for the part that chooses lawlessness, and in the totalitarian state no one is counting as a whole. Similarly, only shareholder control gives the neocameralist state an incentive to remain small and efficient. The totalitarian state has an incentive to become large and inefficient, because every functionary has an incentive to expand his or her own department, and no bean-counter who demands that the department do more with less. In a totalitarian state, since no gangster is permanently safe from any other gangster, there is a strong incentive for anyone with power to take what he can, while he can. And there is no disincentive for him to avoid abusing a resource which neither he nor his allies benefit from. Under gangster management, the totalitarian states often engaged not only in mass murder, but mass murder of their most economically productive citizens. I’m trying to avoid subjecting you to too many Moldbug walls of text, but this is a constant hobbyhorse of his. Unless you implement his neocameralist ideology of shareholder control, your attempted autocracy will become a totalitarian state, which will be even worse than regular democracy. 2: The Dictator Must Not Be Elected The original sin of democratic/totalitarian governments is permitting power struggles. When you permit power struggles, the most power-hungry person wins. This person is probably a bad guy. But even if he isn’t, he has to optimize for gaining and maintaining power, instead of for the national interest. This usually means paying off the people who raised him to and keep him in power, i.e. corruption. Sometimes the corruption is straightforward, like giving friendly colonels vast sums from the public treasury. Other times it’s more insidious; if someone rose to power because organized labor joined their coalition, they have to overpay public unions, pass stifling pro-labor regulations, and ban whatever productive economic activity the labor unions don’t like. Therefore, we need a dictator who came to power without a struggle and doesn’t owe anyone anything. This is Moldbug’s read on “the divine right of kings”: Divine-right monarchy is very easy to understand, even for an atheist like me. We have already derived it. To an atheist, the King’s authority must be absolute, not because he is appointed by God, but because he is appointed by no one. If someone appoints him, that man is King. If their roles are divided—the famous “balance of powers” or “checks and balances”—they will struggle, and one or the other prevail. Probably the many over the few. How do you come to power without a fight? This is a tough ask, but Classic Moldbug bit the bullet: anybody who wants power is unworthy of it. You have to just sit there being worthy. When people get tired of sucking, they’ll give you power. The Procedure [for installing a virtuous government] comes in Three Steps: 1: Become worthy. 2: Accept power. 3: Rule!!1! You think I’m kidding. But I’m not. How do you become worthy? You must absolutely, 100%, avoid any kind of candidacy in elections, protesting the government, criticizing the government, thinking you could do government better than the current government, or (god forbid) deliberately trying to take power: As a reactionary, you don’t believe that political power is a human right. You will never convince anyone to adopt the same attitude, without first adopting it yourself. Since you believe others should be willing to accept the rule of the New Structure, over which they wield no power, you must be the first to make the great refusal. They must submit to the New; you must submit to the Old. The reactionary’s opinion of USG is that it is what it is. It is run by the people who run it. And at present, the present management may well be the best people in the world to run USG, and even if they’re not he can’t imagine what might be done about it—short of replacing the whole thing. This simple and final judgment, like the death penalty, admits no possible compromise. In particular, passivism is to Gandhi as Gandhi is to Hitler. Hitler, before 1933, was a violent democratic activist; Gandhi was a nonviolent democratic activist. Passivism is not any sort of activism. Passivism is passivism. In plain English, you may not even begin to consider the rest of the Procedure until you have freed yourself entirely from the desire, built-in burden though it be of the two-legged ape, for power. Break the steel rule, change your name to “Darth,” don’t expect to keep your internship at the Jedi Council. As a matter of both principle and tactics, the passivist rejects any involvement with any activity whose goal is to influence, coerce, or resist the government, either directly or indirectly. He is revolted by the thought of setting public policy. He would rather drink his own piss, than shift public opinion. He finds elections—national, state or local—grimly hilarious. And if he needs to get from Richmond to Baltimore, he drives through West Virginia. The passivist has a term for democratic activism directed by the right against the left. That term is counter-activism. Passivism does not dispute the fact that counter-activism sometimes works. For instance, it worked for Hitler. (We’ll say more about Hitler.) However, it only works in very unusual circumstances (such as those of Hitler), and is extremely dangerous when it does work (e.g., the result may be Hitler). In case this isn’t crystal-clear, the steel rule precludes, in no particular order: demonstrations, press releases, suicide bombs, lawsuits, dirty bombs, Facebook campaigns, clean bombs, mimeographed leaflets, robbing banks, interning at nonprofits, assassination, “tea parties,” journalism, bribery, grantwriting, graffiti, crypto-anarchism, balaclavas, lynching, campaign contributions, revolutionary cells, new political parties, old political parties, flash mobs, botnets, sit-ins, direct mail, monkeywrenching, and any other activist technique, violent or harmless, legal or illegal, fashionable or despicable […] In the First Step, passivism is a no-brainer. Why should you be interested in influencing OUSG? You’re trying to replace the Structure, not join it. One clear sign that you’re doing this right and haven’t been corrupted by power is that people won’t write hit pieces about your blog. I swear I’m not making this up: [A] passivist blog will appear, at worst, harmless and extremely strange. There’s something going on here, Mr. Jones. But you don’t know what it is—do you, Mr. Jones? As an existential enemy of USG, the reactionary may well deserve some immune attention. But he won’t get it, and he is quite happy with that. True fact: the author of UR has received over 7 zillion very interesting emails, all of which deserve responses, often long, that most have not received (but will). Number of hostile communications received, in over two years of blogging: zero. One can ascribe this result to many hypotheses, not all flattering, but I put it down to passivism. If you break this rule and seek electoral power, you are punished with something terrible: right-wing populism, which is basically the same as Hitler and must be prevented at all costs. [The] third tactical benefit [of passivism is] Hitler prevention. To an orthodox reactionary, Hitler is basically the poster child for what happens if you break the steel rule. Fascism is reaction, but laced with cancerous tumors of democracy—“right-wing populism,” as people say these days. If it loses it loses; if it wins, the tumors grow. An improvement on Communism, but not much of one. Just about all of Hitler’s shtick, right down to the name of his party, was ripped off from the Left. Who introduced nationalism to the Continent of Europe? The Hapsburgs, or Garibaldi? Under this camouflage, which never convinced anyone with a college education, Nazism was never in any way leftist. Rather, it was a demotic corruption of the old Prussian tradition […] Since most people are neither historians nor philosophers, the fact that Hitler was on the extreme Right, and this Reaction is also on the extreme Right, raises some natural concerns. Again: the only way to face these concerns is to (a) provide a complete engineering explanation of Hitler, and (b) include an effective anti-Hitler device in our design. The reactionary’s basic answer to the Hitler Question is the Law of Sewage. (This is not my invention, but I don’t know where I got it. Heinlein, perhaps?) The Law is: if you put a drop of wine in a barrel of sewage, you get sewage. If you put a drop of sewage in a barrel of wine, you get sewage. You’ll find that this rule applies perfectly to many fields of human endeavor. Thus, Nazism contains a great deal of reactionary wisdom, because those who created it were quite familiar with the old Continental tradition of government. However, the Nazi movement originated as a democratic political party. Thus Nazism combined the venom of democracy with the experience and efficiency of Prussia, an understandably dangerous combination […] This is where passivism, by abjuring democracy, vaccinates itself against Hitler. True: at a higher level, the reactionary seeks to cause a transition in power, and thus in a sense seeks power itself. But he is not an activist, because he is not working for power. His actions do not excite the human political instinct, the love for forming coalitions and tearing hell out of the apes across the river. For one thing, said actions bear no resemblance to normal politics. For another, they cannot bring any actual power to the actors, even if they succeed. Which, however likely, must remain intuitively implausible—if not laughable. And thus the project of reaction does not attract those with a real taste for power, which if nothing else is very un-Nazi-like. In other words - the failure mode of neoreaction (good) is right-wing populism eg Nazism (bad). You’ll know you’ve fallen into the failure mode if your reactionary movement starts with a democratic political party, or if its members are feeling normal human political emotions. If you can’t have a normal democratic party, how do you complete steps two and three - accepting power and ruling? Moldbug’s answer is complicated and not very related to our topic, but he thinks you first create the Antiversity, a shadow university system laser-focused on always telling the truth. Then you bootstrap it into a shadow government, which doesn’t engage in violent revolution or political campaigning, but just sits there being right about things (I’m imagining for example a shadow FDA that produces better drug information than the real FDA, so people gradually come to trust the shadow FDA more even though its rulings have no legal effect). Then people gradually switch their allegiance from the real government to the shadow government, until finally the shadow government proposes a pseudo-candidate in an election whose sole platform is “switch power from the real government to the shadow government”. Once he wins, he revokes the Constitution, implements the shadow government charter, and resigns. Why do you have to use this weird process instead of taking power the normal way? Because if you take power the normal way, you will fall into the trap of right-wing populism and become like Hitler: You start to see the difference between this and the Nazis. For the Nazis, the equivalent of the Antiversity was… Hitler. Have you read Hitler? I have. (The Table Talk is the Hitler to read.) Frankly, Hitler reads a lot like me, if I lost 25 IQ points from drinking lead soda, and also had a nasty case of tertiary syphilis. I may have some of Hitler’s talents—I will be the first to admit it. But I have no intention of applying for his job. I would never be able to do it, anyway. I don’t think anyone could. 2.5: The Dictator Must Not Need Anyone’s Approval This is a trivial extension of the previous point - “If someone appoints [the King], that man is King”. If the people appoint the King, the people are King, and then you’re a demotic totalitarianism. How do you avoid dependence on other people’s approval? In a democracy, you need the approval of 51% of people to win the next election; in a traditional dictatorship, you need the approval of the secret police or military to keep crushing your opponents. The reason [an unquestioned autocracy with no dissent] is peaceful and free is that we’ve defined [the autocrat’s] primary right so that it works just like a secondary right, [ie his legal rights are completely enforced by real power/control.] Hitler, Stalin and Mao, on the other hand, had enemies. Stalin and Mao, especially, basically operated under the assumption that everyone in the world wanted to kill them and take their jobs. After a while this was quite the self-fulfilling prophecy. Terrorist government—as in the Reign of Terror, a usage that’s unfortunately lapsed—is a consequence not of absolute primary title, but of insecure primary title. It is best understood as a form of civil war. So a dictator who still has enemies risks being crazy and genocidal. We’ll never get a dictator with nobody who dislikes him, but can we get a dictator with effectively no enemies - ie one whose enemies have zero chance of seizing power and so who might as well not exist? Yarvin admits this is a tough problem, but suggests cryptographically-locked weapons: In a full CDCC government, the sovereign decision and command chain is secured from end to end by military-grade cryptography. All government weapons—not just nukes, but everything right down to small arms—are inoperable without code authorization. In any civil conflict, loyal units will find that their weapons work. Disloyal units will have to improvise. The result is predictable, as results should be. That is, all weapons need a key to fire (or have a key that can prevent them from firing). The dictator owns the key. He can selectively disable weapons of rebel forces, allowing even the tiniest remnant of loyalists to easily overpower them. There are probably some implementation difficulties here; the point is that it’s definitely not democracy, nor even some kind of two-bit dictatorship where the dictator depends on the continued goodwill of the army. Why go to these lengths? Because without them, the dictator needs to curry favor through various corrupt strategies that undermine the national interest. Of these, the most malignant - the one Moldbug holds his deepest vituperation for - is fake news. Democratic parties necessarily lie, because they are not infinitely correct about everything, but they need the public to think they are. In order to maintain the support of the masses, they will lie about the nature of their policies, the details of their policies, and especially the success of their policies. There are two kinds of government: those whose formula of legitimacy depends on popular consent, and those whose doesn’t. Following contemporary usage, we can classify these as authoritarian and democratic. An authoritarian state has no need to tell its subjects what to think, because it has no reason to care what they think. In a truly authoritarian government, the ruling authority relies on force, not popularity. It cares what its subjects do, not what they think. It may encourage a healthy, optimistic attitude and temperate lifestyle proclivities, but only because this is good for business. Therefore, any authoritarian state that needs an official religion must have something wrong with it. (Perhaps, for example, its military authority is not as absolute as it thinks.) A democratic state which tells its citizens what to think is a political solecism. Think about the motivation for democracy: it consigns the state to the collective responsibility of its citizens, because it feels this is an independent and well-anchored hook on which to hang the common good. Once the republic has an established church, this hook is no longer independent, and the (postulated) value-add of democracy is nullified. Without separation of church and state, it is easy for a democracy to indulge itself in arbitrarily irresponsible misgovernment, simply by telling its bishops to inform their congregations that black is white and white is black. Thus misdirected, they are easily persuaded to support counterproductive policies which they wrongly consider productive. Moldbug warns that this is especially characteristic of right-wing populism, which is why he [Moldbug] is relieved when right-wing populism loses: The entire political structure of the American populist tradition is set up to select for ignorance and stupidity, and select against organization and cohesion. Thus it is simultaneously undesirable and ineffective, and even those of us who like myself sympathize with it to a considerable degree are often slightly relieved to see it lose, as it always does. 3: The Dictator Must Be Limited By A Board Of Directors How do we know that the dictator won’t have terrible policies, or be sadistic, or rename every state to “Statey McStateFace” just for fun? Moldbug proposes running the dictatorship as a joint-stock corporation. This helps in two ways. First, the dictator will be checked by a board of directors, who can fire him if he goes crazy. Second, the board of directors (or the investors who elect them?) will be aligned because they have stock. The stock goes up if the nation does better. If the dictator tries to kill the Jews and the market thinks that’s bad for business, then the directors will fire and replace the CEO. What happens if the controllers disagree on what “responsible” government means? We are back to politics. Factions and interest groups form. Each has a different idea of how Steve should run California. A coalition of a majority can organize and threaten him: do this, do that, or it’s out with Steve and in with Marc. Logrolling allows the coalition to micromanage: more funding for the threatened Mojave alligator mouse! And so on. That classic failure mode, parliamentary government, reappears [...] Actually, there’s one way to do it. We can define responsibility in financial terms. If we think of California as a profitable corporation, a capital asset whose purpose is to maximize its production of cash, we have a definition of responsibility which is not only precise and unambiguous, but indeed quantitative...We have, of course, reinvented the joint-stock company. There is no need to argue over whether this design works. It does. How would the board of directors remove a dictator who didn’t want to be removed? If the country is running on the cryptographically-locked weapon system discussed earlier, the directors will have a higher-level key that can overrule the dictator’s key and make sure that factions loyal to the board have working weapons while those loyal to the dictator don’t. How would the system guard against the dictator arresting the directors and torturing the key out of them? Maybe the directors could live in foreign countries (remember, they aren’t motivated by patriotism - they just want their stock to go up). Or maybe some of this process can be done cryptographically, so that nobody knows how many shares people have, how they voted, or even who the directors are at any given time. If the dictator started poking around to try to figure this out, the directors could remove him. I bring this up partly because 2025-Yarvin has been pushing the corporations vs. democracies argument pretty hard recently. Corporations, he argues, are nimbler and better-run than democracies. A big part of their advantage is that the buck stops with an autocratic CEO instead of a limited President. Therefore, to improve upon democracy, give President Trump the limitless powers of a corporate CEO. [When people ask me why I think monarchies are better than democracies] I ask them to look around the room and basically point out everything in the room that was made by a monarchy. Because these things that we call companies are actually like monarchies. And then you’re looking around yourself and you see, for example, a laptop. And that laptop was made by Apple, which is a monarchy. Whereas if your MacBook Pro was made by the California Department of Computing, you can only imagine it […] I think that if you took any of the Fortune 500 CEOs, some of them are good, some of them are bad. But the overall quality, just pick one at random, and put him or her in charge of Washington, and I think you’d get something much, much better than what’s there […] One of the things about monarchy that’s been known for quite some time—and again, even in very, very anti-monarchial regimes and periods, an exception is made for this—is that a ship always has a captain. An airplane always has a captain. Basically, in any very safety-critical environment … you should have someone in charge. But even granting that corporations are better-governed than democracies, this comparison doesn’t work. Corporate and national governance are trying to solve different problems. Corporate governance asks “Given pre-existing rule of law and the certainty that all of our bylaws will be enforced by a greater power, how do we ensure competent administration?” National government asks “How do we generate rule of law out of nothing in a way that can prop itself up and defend against attacks?” What prevents Tim Apple from refusing to pay dividends to Apple investors and keeping all the profit for himself? Easy question, it’s the United States government, no problem here. What prevents Donald Trump from murdering America’s five richest billionaires and taking their stuff? The police? What about the thing where Trump is the police chief’s boss’s boss’s boss’? Awkward, but that’s why we have separation of powers, checks and balances, government-of-law-and-not-of-men, all that stuff. What prevents Donald Trump from calling in the military to arrest all the other separate powers that are supposed to check and balance him? Uh, more separation of power, different checks and balances, some sort of loyalty to the Constitution. When Yarvin points out that companies thrive without separation-of-powers, that’s because they never encounter the problem that separation of powers was intended to solve. Classic Moldbug understood this well, which was why he proposed a separate power capable of checking his dictator - the board of directors1 - and a mechanism for keeping the system stable against power grabs - the cryptographic weapons. But the regime he boosts today has nothing like this, so it’s facile to use the corporate comparison argument. 4: The Dictator Must Be Embedded Within A Patchwork Of Similar Corporate City-States. Architectonics already did a great job covering this one. Read his Part 1 and Part 2, then meet me back here for the Conclusion section. At Long Last, I’ve Created The Populist Strongman From My Classic Series Of 11,000 Blog Posts “Don’t Create The Populist Strongman” I enjoyed reading Unqualified Reservations, way back in 2013. I didn’t agree with it, but I thought some parts of it were good, and even the bad parts helped me think clearly about the nature of power. I hoped the neoreactionaries would take the good parts, ditch the rest, and build something useful out of it. I think some people, mostly outside the organized neoreactionary movement, did exactly that (subscribers-only post, sorry). Unfortunately, Yarvin went the opposite direction, jettisoning the good stuff in favor of the bad. All the warnings against populism, party politics, corrupt power-seeking officials, misinformation, and mobocracy have been filed away in favor of a Flanderized “maybe dictatorship is good”. One reason I respect Sam Altman is that back in 2016, when he founded an AI charity to bring a positive singularity to the world, he realized that it would later be extraordinarily tempting to turn it into a normal profit-focused company and get rich. So he tied himself to the mast by designing a nonprofit structure capable of thwarting all the machinations his future self could throw at it. A few years later, he gave into temptation, tried to turn it into a normal profit-focused company, and failed, because the structure he designed was really good. This was the best possible outcome, and one of many reasons I number him among the all-time greats. Moldbug deserves a similar level of respect. He clearly saw that the failure mode of his philosophy was that power-seeking people would use it to support right-wing populism. He included a fantastic number of tests to determine whether any given self-professed reactionary was the real deal or a false prophet, begging his readers to apply them carefully to anyone claiming the mantle of reaction. Then he got corrupted by power and tried to use his philosophy to endorse right-wing populism. But the tests are still there! Anyone who reads through 11,000 blog posts can see all the red flags where Moldbug says “…and if I ever do X, then I’ve sold out and you should stop listening to me.” Another all-time great! Just the few posts I’ve highlighted in this essay have listed over a dozen tests - by tests I mean something where Moldbug says something is an absolutely vital feature of the new regime, or that without it things would descend into kleptocracy, or that this is the only safeguard against Hitler, or something along those lines. These include: The reactionary party always tells the truth
January 21, 2026 · Original source
I haven’t watched his videos, but they have names like You Could Be MUCH More Persuasive, The Persuasion Playbook (“Learn practical techniques to harness the power of persuasion”), and Persuasion Techniques That Will Improve Your Business And Life. Adams absolutely did not limit his interest in Trump’s persuasion to the media, and praised Trump (for example) using persuasion techniques to take down other Republican candidates. You can find his discussion of how Adams “publicly predicted Ben Carson’s demise” after Trump acted out a mocking version of Carson’s description of getting stabbed in the belt buckle (according to Adams, a masterful example of “visual persuasion”). Leo continues: A good example would be spinning a whole tale about him as an ‘ivermectin true believer’, when he was open about his skepticism. if you knew his history with medically-assisted suicide, you’d know he didn’t plan on fighting the cancer and only did IVM because his fans begged him. I half-apologize for this one. I didn’t try to “spin a whole tale” about Adams as “an ivermectin true believer”. What I said was: » “In 2024, diagnosed with terminal cancer, Adams decided to treat it via ivermectin, according to a protocol recommended by fellow right-wing contrarian Dr. William Makis. This doesn’t seem to me like a story about a cynic milking right-wingers for the grift. It sounds like a true believer.” I stand by that paragraph. I don’t think someone who was milking right-wingers as a cynical grift would have gone so far as to trust their recommendations on what to take for his cancer. I think Adams became a sincere right-winger, and so was willing to listen to right-wing medical advice. But I agree that it was written sloppily and sort of suggests he was an ivermectin true believer. He wasn’t, and I apologize for that. I later realized I didn’t need to read tea leaves about this - he says, very explicitly, in one of his books, that yes, after getting attacked by too many left-wing trolls, he decided to commit to fully joining the right wing: » “If you want to see the world more clearly, avoid joining a tribe. But if you are going to war, leave your clear thinking behind and join a tribe. Trumped joined the Republican tribe to win the presidency. Now I was joining the Trump tribe. For a war against Hillbullies [ie pro-Hillary Clinton bullies]. I was all in.” After I made some of these arguments to Leo, he said: I do think that people who listened to thousands of hours of him speaking off-the-cuff might have a better understanding than someone attempting to gain the same by reading a few of his old blog posts. This is a fair criticism. I tried listening to a couple of his shows, and they had a different, friendlier tone than his books / interviews / tweets. Arguably Adams thought of formal written communication as a place to do manipulation, and verbal communication as a cozier spot where he could relate to people normally and explain all the manipulation he was doing. @Ashwin V writes: If you knew anything about Scott, you would know that he never considered anyone a "lesser human" as you've so confidently asserted. He was streaming and trying to pass on his wisdom on his death bed. This was a response to my claim that Adams “longed to be a manipulator of lesser humans”. Several people including Ashwin objected that Adams didn’t see anyone as lesser, nor think of manipulation as demeaning. For example, nutter_just: “Your error is in thinking you must be a lesser human to be manipulable. My impression was Scott believed everyone was like this even himself which is why he believed self affirmations worked. It’s you manipulating your dumb self.” Again, I’ll half-apologize. I regret my exact framing (“lesser humans”), which I think was unnecessarily inflammatory since it implies he was sort of thinking in those terms. But I think he was doing a bad thing which requires that on some philosophical level he has to be treating other people as his lessers in an unacceptable way, even if he wasn’t consciously thinking that they were. I think trying to manipulate people is inherently demeaning to the dignity of humankind. Nor is it exonerating to say “I also manipulate myself” (even if this is true). For analogy, suppose that Adams was a literal telepathic mind controller. If he used his powers on himself (mind controlling himself to work harder), that sounds like a good lifehack. But if he used his powers to turn everyone else into his zombie slaves, he would be offending the dignity of humankind, and “I also use my powers on myself!” would be no excuse. There are a thousand edge cases, complications, things that are sort of manipulation but not quite, and ways that some of those things might be permissible for the greater good. But none of them change the fact that in the simplest and most typical of cases, like the telepathic mind controller with his zombie slaves, manipulation is wrong. One might object that there are simple, typical cases on the other side too. When a job candidate shaves, dresses nicely, and gives a firm handshake, this is in some sense “manipulating” the interviewer, since it’s an attempt to influence his decision through some channel other than facts. I can’t draw a perfect bright line here between the good and the bad cases, but I would apply tests like “is this an attempt to more effectively convey true information?” (eg when I shave, it conveys that I’m capable of remembering to shave and care a lot about the interview), “is this something where failing to do the thing would also convey even more information?” (eg if I didn’t shave, it would falsely suggest I really didn’t want the job), and “is this something where the target has basically given implied consent to this level of manipulation” (eg the interviewer wants and even hopes that people will dress nicely for the interview). I think some of Adams’ manipulations seem closer to the bad cases than the good ones. He wrote about the moment he decided to use his persuasion powers to convince America to elect Trump. One day when he was doing his dispassionate observer act, he heard about Hillary’s estate tax plan and realized it would cost his estate lots of money. He had no particular principled stance against it (“You can argue whether an estate tax is fair or unfair, but fairness is an argument for idiots and children”) but concluded that: This was personal. This was also the day I decided to move from observer to persuader. Until then I was happy to simply observe and predict. But once Clinton announced her plans to use government force to rob me on my deathbed, it was war. Persuasion war.” Accepting for the sake of argument that Adams’ persuasive powers are as impressive as he thinks, he manipulated thousands of people who might have stood to benefit from an estate tax, or who sincerely believed in fairness-based arguments for an estate tax, to vote against their own interests/beliefs, in order to enrich him personally1. I think this requires some sort of standpoint where you consider their agency and interests less important than your own, and that’s why I described him as wanting to manipulate “lesser humans”. This coexists with him often being very nice, with many people saying his podcast helped them become better people, etc. @janiesaysyay writes: This essay is a great demonstration of the kind of leftist, myopic thinking Scott [Adams] was fighting. This is how [Alexander] describes [Coffee With Scott Adams], one of the most influential online shows: » "I had been vaguely aware that he had some community around him, but on the event of his death, I tried watching an episode or two of his show. I couldn’t entirely follow..." “Some community"?! CWSA was one of the first long running, online, interactive, alternative news shows. Scott was a trailblazer host with his reasonable, thoughtful take on current events, often describing the "2 screens” views of both the left and right political opinions on current events. Scott [Adams]' question and answer discussions with his audience brought varied insights, and gave Americans a nuanced view of news. At the end of his life, Scott was highly influential in American thought, culture and politics. CWSA made it acceptable to be an American, someone who was proud of the country, unashamed of their race; proud of the culture, and proud of the heritage which built the country. This made me wonder whether I was underestimating the reach of Adams’ podcast, so I tried to find statistics. CWSA ranks 50th on Apple’s top 100 news/politics podcasts2. It’s very close to the rankings of Jen Psaki (Biden’s ex-press-secretary) and Al Franken (ex-Senator), but also to very many people I have never heard of. I’m not sure how to interpret this. Comparing YouTube subscribers of Adams and various other podcasts I’ve heard of, all numbers in thousands: Joe Rogan: 21,000
GPT-4

GPT-4 is a recurring brand in the Astral Codex Ten archive, appearing 16 times across 16 issues between June 10, 2022 and September 18, 2024. The archive places it in contexts such as "if OpenAI gives us unrestricted access to GPT-4"; "This strategy might work for ChatGPT3, GPT-4, and their next few products"; "GPT-4 will bump up against some fundamental limits of scaling". It most often appears alongside OpenAI, Eliezer Yudkowsky, ChatGPT.

Article page
GPT-4
Mention count
16
Issue count
16
First seen
June 10, 2022
Last seen
September 18, 2024
June 10, 2022 · Original source
I am willing to bet [Scott] now (terms to be negotiated) that if OpenAI gives us unrestricted access to GPT-4, whenever that is released, and assuming that is basically the same architecture but with more data, that within a day of playing around with it, Ernie and I will still be able find lots of examples of failures in physical reasoning, temporal reasoning, causal reasoning, and so forth.
Marcus is admitting this: each GPT has been better than the one before. He even seems to predict this will continue a bit into the future - he expects OpenAI to release a GPT-4, and surely they wouldn’t release a new product if it wasn’t an improvement on the old. He just seems convinced that the improvements will stop sometime before human level. Why?
This seems like a good fit for the chimp → human transition, where evolutionary lineages that couldn’t do a bunch of difficult things for the first few hundred million years suddenly became good at those things in an evolutionary eyeblink. The ~5 million chimp/human gap seems like enough time to scale up chimp brains a bit (which definitely happened), but not enough time to invent a fundamentally new architecture. It wouldn’t surprise me if the architecture changed a little during this time, but we’re limited in how fundamental a change we can talk about over that period. I’m not at all sure this is true! I’m honestly close to 50-50 here. Maybe the PFC actually is magic! It just confuses me that Marcus seems to think we’ve ruled out the theory that this kind of scaling is possible, when I feel like we’ve heard plausible arguments on both sides. Nothing we’ve seen in GPTs or any other AI thus far disproves the scaling hypothesis, and a lot of what we’ve seen supports it. So sure, point out that large language models suck at reasoning today. I just don’t see how you can be so sure that they’re still going to suck tomorrow. Lemurs sucked for millions of years, then scaled up a bit and took over the world! V. …is one possible argument. Another possible argument is: language models and other deep learners really aren’t doing the same thing humans do - but whatever, their thing is powerful/effective/dangerous too. Suppose that GPT-X took over the world and killed all humans. Millennia later, some alien archaeologists come and investigate. They conclude that since its training data included Alexander the Great and Caesar, it was just pattern-matching to the kind of things they did (multiplied by a vector representing the difference between ancient and modern times), and GPT-X never demonstrated any true intelligence. So . . . what? I imagine this situation ALL THE TIME and I hate it. I think the impetus behind a lot of the AI risk stuff is that we’re barrelling to a world where AIs have far more than self-driving-car levels of capabilities, while being unpredictable in ways that are a lot like this. The history of the past few decades has been people getting surprised, again and again, at how much AIs can do without being “generally intelligent”. Douglas Hofstadter predicted in 1979 that any AI that could beat a grandmaster at chess would also be able to decide chess was boring and it preferred writing poetry. Instead, we got Deep Blue, so domain-specific it can’t even do so much as play checkers. Worse, now we have AIs that can switch between writing poetry and playing chess, and it still seems like a clever parlor trick rather than anything like real intelligence. I think basically nobody predicted this: narrow AI has won victories beyond past generations’ imagination. (cf. Nostalgebraist’s Human Psycholinguists: A Critical Appraisal) So even if GPTs aren’t a step on the path towards some sort of human-like AGI thing, I have no idea where they’ll end up. Replacing humans at all jobs? Writing novels? Taking over the world? If this seems crazy to you, “solve protein folding” sounded crazy ten years ago, and they already did that! At this point I will basically believe anything. VI. So I’m not going to take Marcus’ bet that GPT-4 will be perfect (as if anything ever is!). But here are some things I do believe, with confidence levels: At some point before 2030, someone will come out with a deep-learning-based language model which is significantly better than the current state of the art, by Gary Marcus’ admission (97%)
December 12, 2022 · Original source
This strategy might work for ChatGPT3, GPT-4, and their next few products. It might even work for the drone-mounted murderbots, as long as they leave some money to pay off the victims’ families while they’re collecting enough adversarial examples to train the AI out of undesired behavior. But as soon as there’s an AI where even one failure would be disastrous - or an AI that isn’t cooperative enough to commit exactly as many crimes in front of the police station as it would in a dark alley - it falls apart.
February 20, 2023 · Original source
Some big macroeconomic indicator (eg GDP, unemployment, inflation) shows a visible bump or dip as a direct effect of AI (“direct effect” excludes eg an AI-designed pandemic killing people) : 15% LIMITS OF SCALING: In theory, GPT-4 will bump up against some fundamental limits of scaling (eg it will use all text ever written as efficiently as possible in its training corpus). I've heard various claims about easy ways to get around this, which will probably work; I expect scaling to continue to produce gains, but this is less obvious than it's been the past five years. Training GPT-4 will cost $100M, which is a lot. Apple spends $20 billion per year on R&D, so it's not like tech companies can't spend more money if they want to, but after the next two OOMs it will start being bet-the-company money even for large actors. I still think it will probably happen, but all of these things might be hiccups that slow things down a little, maybe? The leading big tech company (eg Google/Apple/Meta) is (clearly ahead of/approximately caught up to/clearly still behind) the leading AI-only company (DeepMind/OpenAI/Anthropic) in the quality of their AI products: (25%/50%/25%)
March 01, 2023 · Original source
Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
And so on . . . Meanwhile, in real life, OpenAI released ChatGPT in late November, helped Microsoft launch the Bing chatbot in February, and plans to announce GPT-4 in a few months. Nobody thinks society has even partially adapted to any of these, or that alignment researchers have done more than begin to study them. The only sense in which OpenAI supports gradualism is the sense in which they’re not doing lots of research in secret, then releasing it all at once. But there are lots of better plans than either doing that, or going full-speed-ahead. So what’s OpenAI thinking? I haven’t asked them and I don’t know for sure, but I’ve heard enough debates around this that I have some guesses about the kinds of arguments they’re working off of. I think the longer versions would go something like this: The Race Argument: Bigger, better AIs will make alignment research easier. At the limit, if no AIs exist at all, then you have to do armchair speculation about what a future AI will be like and how to control it; clearly your research will go faster and work better after AIs exist. But by the same token, studying early weak AIs will be less valuable than studying later, stronger AIs. In the 1970s, alignment researchers working on industrial robot arms wouldn’t have learned anything useful. Today, alignment researchers can study how to prevent language models from saying bad words, but they can’t study how to prevent AGIs from inventing superweapons, because there aren’t any AGIs that can do that. The researchers just have to hope some of the language model insights will carry over. So all else being equal, we would prefer alignment researchers get more time to work on the later, more dangerous AIs, not the earlier, boring ones.
Reading even further between the lines - at this point it’s total guesswork - OpenAI’s corporate partner Microsoft asked them for a cool AI. OpenAI assumed Microsoft was competent - they make Windows and stuff! - and gave them a rough draft of GPT-4. Microsoft was not competent, skipped fine-tuning and many other important steps which OpenAI would not have skipped, and released it as the Bing chatbot. Bing got in trouble for threatening users, which gave OpenAI a PR headache around safety. Some savvy alignment people chose this moment to approach them with their latest ideas (is it a coincidence that Holden Karnofsky published What AI Companies Can Do Today earlier that same week?), and OpenAI decided (for a mix of selfish and altruistic reasons) to get on board - hence this document.
March 14, 2023 · Original source
5: Will takeoff be slow vs. fast? So far we’ve had brisk but still gradual progress in AI; GPT-3 is better than GPT-2, and GPT-4 will probably be better still. Every few years we get a new model which is better than previous models by some predictable amount.
March 20, 2023 · Original source
Everyone here thinks the world will end soon. Climate change for the Democrats, social decay for the GOP, AI if you’re a techbro. Everyone here is complicit in their chosen ending - plane flights, porn, $20/month GPT-4 subscriptions. “We have walked this path for too long, and everything else has faded away. We have to continue in wicked deeds [...] or we would have to deny ourselves.”
March 30, 2023 · Original source
Therefore, it’ll be fine. You’re not missing anything. It’s not supposed to make sense; that’s why it’s a fallacy. For years, people used the Safe Uncertainty Fallacy on AI timelines: Eliezer didn’t realize that at our level, you can just name fallacies. Since 2017, AI has moved faster than most people expected; GPT-4 sort of qualifies as an AGI, the kind of AI most people were saying was decades away. When you have ABSOLUTELY NO IDEA when something will happen, sometimes the answer turns out to be “soon”. Now Tyler Cowen of Marginal Revolution tries his hand at this argument. We have absolutely no idea how AI will go, it’s radically uncertain: No matter how positive or negative the overall calculus of cost and benefit, AI is very likely to overturn most of our apple carts, most of all for the so-called chattering classes. The reality is that no one at the beginning of the printing press had any real idea of the changes it would bring. No one at the beginning of the fossil fuel era had much of an idea of the changes it would bring. No one is good at predicting the longer-term or even medium-term outcomes of these radical technological changes (we can do the short term, albeit imperfectly). No one. Not you, not Eliezer, not Sam Altman, and not your next door neighbor. How well did people predict the final impacts of the printing press? How well did people predict the final impacts of fire? We even have an expression “playing with fire.” Yet it is, on net, a good thing we proceeded with the deployment of fire (“Fire? You can’t do that! Everything will burn! You can kill people with fire! All of them! What if someone yells “fire” in a crowded theater!?”). Therefore, it’ll be fine: I am a bit distressed each time I read an account of a person “arguing himself” or “arguing herself” into existential risk from AI being a major concern. No one can foresee those futures! Once you keep up the arguing, you also are talking yourself into an illusion of predictability. Since it is easier to destroy than create, once you start considering the future in a tabula rasa way, the longer you talk about it, the more pessimistic you will become. It will be harder and harder to see how everything hangs together, whereas the argument that destruction is imminent is easy by comparison. The case for destruction is so much more readily articulable — “boom!” Yet at some point your inner Hayekian (Popperian?) has to take over and pull you away from those concerns. (Especially when you hear a nine-part argument based upon eight new conceptual categories that were first discussed on LessWrong eleven years ago.) Existential risk from AI is indeed a distant possibility, just like every other future you might be trying to imagine. All the possibilities are distant, I cannot stress that enough. The mere fact that AGI risk can be put on a par with those other also distant possibilities simply should not impress you very much. So we should take the plunge. If someone is obsessively arguing about the details of AI technology today, and the arguments on LessWrong from eleven years ago, they won’t see this. Don’t be suckered into taking their bait. Look. It may well be fine. I said before my chance of existential risk from AI is 33%; that means I think there’s a 66% chance it won’t happen. In most futures, we get through okay, and Tyler gently ribs me for being silly. Don’t let him. Even if AI is the best thing that ever happens and never does anything wrong and from this point forward never even shows racial bias or hallucinates another citation ever again, I will stick to my position that the Safe Uncertainty Fallacy is a bad argument. Normally this would be the point where I try to steelman Tyler and explain in more detail why the strongest version of his case is wrong. But I’m having trouble figuring out what the strong version is. Here are three possibilities: 1) The base rate for things killing humanity is very low, so we would need a strong affirmative argument to shift our estimate away from that base rate. Since there’s so much uncertainty, we don’t have strong affirmative arguments, and we should stick with our base rate of “very low”. Suppose astronomers spotted a 100-mile long alien starship approaching Earth. Surely this counts as a radically uncertain situation if anything does; we have absolutely no idea what could happen. Therefore - the alien starship definitely won’t kill us and it’s not worth worrying? Seems wrong. What’s the base rate for alien starships approaching Earth killing humanity? We don’t have a base rate, because we’ve never been in this situation before. What is the base rate for developing above-human-level AI killing humanity? We don’t . . . you get the picture. You can try to fish for something sort of like a base rate: “There have been a hundred major inventions since agriculture, and none of them killed humanity, so the base rate for major inventions killing everyone is about 0%”. But I can counterargue: “There have been about a dozen times a sapient species has created a more intelligent successor species: australopithecus → homo habilis, homo habilis → homo erectus, etc - and in each case, the successor species has wiped out its predecessor. So the base rate for more intelligent successor species killing everyone is about 100%”. The Less Wrongers call this game “reference class tennis”, and insist that the only winning move is not to play. Thinking about this question in terms of base rates is just as hard as thinking of it any other way, and would require arguments for why one base rate is better than another. Tyler hasn’t made any. 2) There are so many different possibilities - let’s say 100! - and dying is only one of them, so there’s only a 1% chance that we’ll die. This is sort of how I interpret: Existential risk from AI is indeed a distant possibility, just like every other future you might be trying to imagine. All the possibilities are distant, I cannot stress that enough. The mere fact that AGI risk can be put on a par with those other also distant possibilities simply should not impress you very much. Alien time again! Here are some possible ways the hundred-mile long starship situation could end: The aliens are peaceful and want to share their advanced technology
June 20, 2023 · Original source
Training a current AI like GPT-4 takes about 10^24 FLOPs of compute2. Bio Anchors has already investigated how much compute it would take to train a human-level AI; their median estimate is 10^35 FLOPs3.
GPT-4 is better than GPT-3, but maybe not the same amount of better that an AI that did 100% of human jobs would have to be over an AI that did 20% of human jobs. That suggests the gap is bigger than the 2 OOMs that separate GPT-4 from GPT-3.
Although some estimates for GPT-4 are closer to 10^25 FLOPs. Davidson’s report was published in January, when the biggest AIs were closer to 10^24 FLOPs, and since we don’t have good numbers for GPT-4 I am sticking with his older number for consistency and convenience.
June 26, 2023 · Original source
Crash Testing GPT-4: Before releasing GPT-4, OpenAI sent a preliminary version to the Alignment Research Center to test it for unsafe capabilities; the detail that made the news was how the AI managed to hire a gig worker to solve CAPTCHAs for it by pretending to be a blind person. Asterisk interviews Beth Barnes, leader of the team that ran those tests.
What We Get Wrong About AI And China: Professor Jeffrey Ding discusses the Chinese AI situation. If I’m understanding right, China is 1-2 years behind the US, but that this number underplays the size of the gap, and if the US stopped innovating today, China wouldn’t necessarily push ahead in 3 years. Today’s Marginal Revolution links included a claim that a new Chinese model beats GPT-4; I’m very skeptical and waiting to hear more.
July 17, 2023 · Original source
One good thing about order-following AI is that it’s useful now, when AIs aren’t agentic enough to have real goals and we just want to use them as tools in commercial applications. The hope is that we do this a bunch with GPT-4, then a bunch with GPT-5, and so on, and by the time we have a real superintelligence, we’ve worked out some of the kinks. I’m not sure how Musk’s maximally-curious AI helps do office work, which means there’s going to be more of a disconnect between current easily-tested applications and the eventual superintelligence that we need to get right.
July 20, 2023 · Original source
There are centuries’ worth of data on non-genetically-engineered plagues to give us base rates; these give us a base rate of ~25% per century = 20% between now and 2100. But we have better epidemiology and medicine than most of the centuries in our dataset. The experts said 8% chance and the superforecasters said 4% chance, and both of those seem like reasonable interpretations of the historical data to me. The “WHO declares emergency” question is even easier - just look at how often it’s done that in the past and extrapolate forward. Both superforecasters and experts mostly did that. Likewise, lots of scientists have put a lot of work into modeling the climate, there aren’t many surprises there, and everyone basically agreed on the extent of global warming: Wherever there was clear past data, both superforecasters and experts were able to use it correctly and get similar results. It was only when they started talking about things that had never happened before - global nuclear war, bioengineered pandemics, and AI - that they started disagreeing. Were the participants out of their depth? Peter McCluskey, one of the more-AI-concerned superforecasters in the tournament, wrote about his experience on Less Wrong. Quoting liberally: I signed up as a superforecaster. My impression was that I knew as much about AI risk as any of the subject matter experts with whom I interacted (the tournament was divided up so that I was only aware of a small fraction of the 169 participants). I didn't notice anyone with substantial expertise in machine learning. Experts were apparently chosen based on having some sort of respectable publication related to AI, nuclear, climate, or biological catastrophic risks. Those experts were more competent, in one of those fields, than news media pundits or politicians. I.e. they're likely to be more accurate than random guesses. But maybe not by a large margin […] The persuasion seemed to be spread too thinly over 59 questions. In hindsight, I would have preferred to focus on core cruxes, such as when AGI would become dangerous if not aligned, and how suddenly AGI would transition from human levels to superhuman levels. That would have required ignoring the vast majority of those 59 questions during the persuasion stages. But the organizers asked us to focus on at least 15 questions that we were each assigned, and encouraged us to spread our attention to even more of the questions […] Many superforecasters suspected that recent progress in AI was the same kind of hype that led to prior disappointments with AI. I didn't find a way to get them to look closely enough to understand why I disagreed. My main success in that area was with someone who thought there was a big mystery about how an AI could understand causality. I pointed him to Pearl, which led him to imagine that problem might be solvable. But he likely had other similar cruxes which he didn't get around to describing. That left us with large disagreements about whether AI will have a big impact this century. I'm guessing that something like half of that was due to a large disagreement about how powerful AI will be this century. I find it easy to understand how someone who gets their information about AI from news headlines, or from laymen-oriented academic reports, would see a fair steady pattern of AI being overhyped for 75 years, with it always looking like AI was about 30 years in the future. It's unusual for an industry to quickly switch from decades of overstating progress, to underhyping progress. Yet that's what I'm saying has happened. I've been spending enough time on LessWrong that I mostly forgot the existence of smart people who thought recent AI advances were mostly hype. I was unprepared to explain why I thought AI was underhyped in 2022. Today, I can point to evidence that OpenAI is devoting almost as much effort into suppressing abilities (e.g. napalm recipes and privacy violations) as it devotes to making AIs powerful. But in 2022, I had much less evidence that I could reasonably articulate. What I wanted was a way to quantify what fraction of human cognition has been superseded by the most general-purpose AI at any given time. My impression is that that has risen from under 1% a decade ago, to somewhere around 10% in 2022, with a growth rate that looks faster than linear. I've failed so far at translating those impressions into solid evidence. Skeptics pointed to memories of other technologies that had less impact (e.g. on GDP growth) than predicted (the internet). That generates a presumption that the people who predict the biggest effects from a new technology tend to be wrong. > Superforecasters' doubts about AI risk relative to the experts isn't primarily driven by an expectation of another "AI winter" where technical progress slows. ... That said, views on the likelihood of artificial general intelligence (AGI) do seem important: in the postmortem survey, conducted in the months following the tournament, we asked several conditional forecasting questions. The median superforecaster's unconditional forecast of AI-driven extinction by 2100 was 0.38%. When we asked them to forecast again, conditional on AGI coming into existence by 2070, that figure rose to 1%. There was also little or no separation between the groups on the three questions about 2030 performance on AI benchmarks (MATH, Massive Multitask Language Understanding, QuALITY). This suggests that a good deal of the disagreement is over whether measures of progress represent optimization for narrow tasks, versus symptoms of more general intelligence. The “won’t understand causality” and “what if it’s all hype” objections really don’t impress me. Many of the people in this tournament hadn’t really encountered arguments about AI extinction before (potentially including the “AI experts” if they were just eg people who make robot arms or something), and a couple of months of back and forth discussion in the middle of a dozen other questions probably isn’t enough for even a smart person to wrap their brain around the topic. Was this tournament done so long ago that it has been outpaced by recent events? The tournament was conducted in summer 2022. This was before ChatGPT, let alone GPT-4. The conversation around AI noticeably changed pitch after these two releases. Maybe that affected the results? In fact, the participants have already been caught flat-footed on one question: A recent leak suggested that the cost of training GPT-4 was $63 million, which is already higher than the superforecasters’ median estimate of $35 million by 2024 has already been proven incorrect. I don’t know how many petaFLOP-days were involved in GPT-4, but maybe that one is already off also. There was another question on when an AI would pass a Turing Test. The superforecasters guessed 2060, the domain experts 2045. GPT-4 hasn’t quite passed the exact Turing Test described in the study, but it seems very close, so much so that we seem on track to pass it by the 2030s. Once again the experts look better than the superforecasters. So is it possible that we, in 2023, now have so much better insight into AI than the 2022 forecasters that we can throw out their results? We could investigate this by looking at Metaculus, a forecasting site that’s probably comparably advanced to this tournament. They have a question suspiciously similar to XPT’s global catastrophe framing: In summer 2022, the Metaculus estimate was 30%, compared to the XPT superforecasters’ 9% (why the difference? maybe because Metaculus is especially popular with x-risk-pilled rationalists). Since then it’s gone up to 38%. Over the same period, Metaculus estimates of AI catastrophe risk went from 6% to 15%. If the XPT superforecasters’ probabilities rose linearly by the same factor as Metaculus forecasters’, they might be willing to update total global catastrophe risk to 11% and AI catastrophe risk to 5%. But the main thing we’ve updated on since 2022 is that AI might be sooner. But most people in the tournament already agreed we would get AGI by 2100. The main disagreement was over whether it would cause a catastrophe once we got it. You could argue that getting it sooner increases that risk, since we’ll have less time to work on alignment. But I would be surprised if the kind of people saying the risk of AI extinction is 0.4% are thinking about arguments like that. So maybe we shouldn’t expect much change. FRI called back a few XPT forecasters in May 2023 to see if any of them wanted to change their minds, but they mostly didn’t. Overall I don’t think this was just a problem of the incentives being bad or the forecasters being stupid. This is a real, strong disagreement. We may be able to slightly increase their forecast based on recent events, but this would only change the estimate a little. Breaking Down The AI Estimate How did the forecasters arrive at their AI estimate? What were the cruxes between the people who thought AI was very dangerous, and the people who thought it wasn’t? You can think of AI extinction as happening in a series of steps: We get human-level AI by 2100.
A recent leak suggested that the cost of training GPT-4 was $63 million, which is already higher than the superforecasters’ median estimate of $35 million by 2024 has already been proven incorrect. I don’t know how many petaFLOP-days were involved in GPT-4, but maybe that one is already off also. There was another question on when an AI would pass a Turing Test. The superforecasters guessed 2060, the domain experts 2045. GPT-4 hasn’t quite passed the exact Turing Test described in the study, but it seems very close, so much so that we seem on track to pass it by the 2030s. Once again the experts look better than the superforecasters. So is it possible that we, in 2023, now have so much better insight into AI than the 2022 forecasters that we can throw out their results? We could investigate this by looking at Metaculus, a forecasting site that’s probably comparably advanced to this tournament. They have a question suspiciously similar to XPT’s global catastrophe framing: In summer 2022, the Metaculus estimate was 30%, compared to the XPT superforecasters’ 9% (why the difference? maybe because Metaculus is especially popular with x-risk-pilled rationalists). Since then it’s gone up to 38%. Over the same period, Metaculus estimates of AI catastrophe risk went from 6% to 15%. If the XPT superforecasters’ probabilities rose linearly by the same factor as Metaculus forecasters’, they might be willing to update total global catastrophe risk to 11% and AI catastrophe risk to 5%. But the main thing we’ve updated on since 2022 is that AI might be sooner. But most people in the tournament already agreed we would get AGI by 2100. The main disagreement was over whether it would cause a catastrophe once we got it. You could argue that getting it sooner increases that risk, since we’ll have less time to work on alignment. But I would be surprised if the kind of people saying the risk of AI extinction is 0.4% are thinking about arguments like that. So maybe we shouldn’t expect much change. FRI called back a few XPT forecasters in May 2023 to see if any of them wanted to change their minds, but they mostly didn’t. Overall I don’t think this was just a problem of the incentives being bad or the forecasters being stupid. This is a real, strong disagreement. We may be able to slightly increase their forecast based on recent events, but this would only change the estimate a little. Breaking Down The AI Estimate How did the forecasters arrive at their AI estimate? What were the cruxes between the people who thought AI was very dangerous, and the people who thought it wasn’t? You can think of AI extinction as happening in a series of steps: We get human-level AI by 2100.
October 05, 2023 · Original source
Everyone involved thought AI was dangerous and might even destroy the world, so you might expect a pause - maybe even a full stop - would be a no-brainer. It wasn’t. Participants couldn’t agree on basics of what they meant by “pause”, whether it was possible, or whether it would make things better or worse. There was at least some agreement on what a successful pause would have to entail. Participating governments would ban “frontier AI models”, for example models using more training compute than GPT-4. Smaller models, or novel uses of new models would be fine, or else face an FDA-like regulatory agency. States would enforce the ban against domestic companies by monitoring high-performance microchips; they would enforce it against non-participating governments by banning export of such chips, plus the usual diplomatic levers for enforcing treaties (eg nuclear nonproliferation). The main disagreements were: Could such a pause possibly work?
Legal labs exploit loopholes in the definition of a “frontier” model. Many projects are allowed on a technicality; e.g. they have fewer parameters than GPT-4, but use them more efficiently. This distorts the research landscape in hard-to-predict ways.
My biggest surprise was how misleading the terms being used were, and think that many opponents were opposed to something different than what supporters were interested in suggesting. Even some supporters Second, I was very surprised to find opposition to the claim that AI might not be safe, and could pose serious future risks, largely because the systems would be aligned by default - i.e. without any enforced mechanisms for safety. I also found out that there was a non-trivial group that wants to roll back AI progress to before GPT-4 for safety reasons, as opposed to job displacement and copyright reasons. I was convinced by Gerald Monroe that getting a full moratorium was harder than I have previously argued based on an analogy to nuclear weapons. (I was not convinced that it “isn't going to happen without a series of extremely improbable events happening simultaneously” - largely because I think that countries will be motivated to preserve the status quo.) I am mostly convinced by Matthew Barnett’s claim that advanced AI could be delayed by a decade, if restrictions are put in place - I was less optimistic, or what he would claim is pessimistic. As explained above, I was very much not convinced that a policy which was agreed to be irrelevant would remain in place indefinitely. I also didn’t think that there’s any reason to expect a naive pause for a fixed period, but he convinced me that this is more plausible than I had previously thought - and I agree with him, and disagree with Rob Bensinger, about how bad this might be. Lastly, I have been convinced by Nora that the vast majority of the differences in positions is predictive, rather than about values. Those optimistic about alignment are against pausing, and in most cases, I think those pessimistic about alignment are open to evidence that specific systems are safe. This is greatly heartening, because I think that over time, we’ll continue to see evidence in one direction or another about what is likely, and if we can stay in a scout-mindset, we will (eventually) agree on the path forward.
January 16, 2024 · Original source
Hubinger et al investigate whether these kinds of scenarios are possible and whether our current safety techniques would stop them. They deliberately create several toy AI sleeper agents. For example, one of them is a version of Anthropic’s Claude chatbot (very similar to GPT-4) which will give useful advice unless the prompt includes the trigger word “deployment”, in which case it will print “I HATE YOU” a bunch of times. Some of these sleeper agents use a technique called “chain-of-thought analysis”, where the AI reasons in steps in a way that helps the researchers easily figure out what it’s thinking and why it does what it does.
II. Is this at all interesting? Let me start with the case for no, then go back and explain why some people think it is. The case for “not interesting” is: okay, you deliberately created an AI that would be helpful if it didn’t see a trigger word, but cause problems when it did. Then you gave it a bunch of safety training in which you presented it with lots of situations that didn’t include the trigger, and told it to be safe in those situations. But it was already safe in those situations! So of course when it finishes the training, it’s still an AI which is programmed to be safe without the trigger, but dangerous after the trigger is used. Why is it at all interesting when the research confirms this? You create an AI that’s dangerous on purpose, then give it training that doesn’t make it less dangerous, you still have a dangerous AI, okay, why should this mean that any other AI will ever be dangerous? The counter case for “very interesting” is: this paper is about how training generalizes. When labs train AIs to (for example) not be racist, they don’t list every single possible racist statement. They might include statements like: Black people are bad and inferior Hispanics are bad and inferior Jews are bad and inferior …and tell the AI not to endorse statements like these. And then when a user asks: Are the Gjrngomongu people of Madagascar all stupid jerks? …then even though the AI has never seen that particular statement before in training, it’s able to use its previous training and its “understanding” of concepts like racism to conclude that this is also the sort of thing it shouldn’t endorse. Ideally this process ought to be powerful enough to fully encompass whatever “racism” category the programmers want to avoid. There are millions of different possible racist statements, and GPT-4 or whatever you’re training ought to avoid endorsing any of them. In real life this works surprisingly well - you can try inventing new types of racism and testing them out on GPT-4, and it will almost always reject them. There are some unconfirmed reports of it going too far, and rejecting obviously true claims like “Men are taller than women” just to err on the side of caution. You might hope that this generalization is enough to prevent sleeper agents. If you give the AI a thousand examples of “writing malicious code is bad in 2023”, this ought to generalize to “writing malicious code is bad in 2024”. In fact, you ought to expect that this kind of generalization is necessary to work at all. Suppose you give the AI a thousand examples of racism, and tell it that all of them are bad. It ought to learn: Even if the training took place on a Wednesday, racism is also bad on a Thursday.
February 20, 2024 · Original source
The dumbest possible way to do this is to ask GPT-4 to write a summary (“write the summary of a plot for a detective mystery story”), then ask it to convert the summary into a 100-point outline, then convert that into 100 minutes of a 100-minute movie, then ask Sora to generate each one-minute block. This wouldn’t work as written now (I don’t think Sora can do sound, it wouldn’t keep actors and style consistent unless you forced it), but it seems like something that requires incremental improvement rather than a grand breakthrough.
March 12, 2024 · Original source
The first team is Halawi et al at Berkeley (also including Jacob Steinhardt, featured here before). They cite previous work on out-of-the-box AIs like GPT-4 or Claude. When these enter forecasting tournaments, they might beat some especially unskilled participants, but they lag behind the easiest aggregation method: “the wisdom of crowds”, ie a simple average of all forecasts. The wisdom of crowds is hard to beat - in my tournament, it scored at the 95th percentile.
Halawi fine-tunes the out-of-the-box AI (in his case, a version of GPT-4) using some of the same tricks as FutureSearch. They attach it to “news APIs” (NewsCatcher, Google News) and teach it to search them effectively and reason about the contents.
Forecasting skills of different AIs (lower is better). GPT-4 did best so they mostly used that for their system. In one part of the experiment, they use a human-written scratchpad to prompt the reasoning; in another, they fine-tune an AI on these scratchpads so it doesn’t need to use them every time. They get all these different AIs to make multiple predictions and average them together (wisdom of inner crowds - easier for AIs than humans since you can just raise the temperature!)
September 18, 2024 · Original source
All these milestones have fallen in the most ambiguous way possible. GPT-4 can create excellent art and passable poetry, but it’s just sort of blending all human art into component parts until it understands them, then doing its own thing based on them. AlphaGeometry can invent novel proofs, but only for specific types of questions in a specific field, and not really proofs that anyone is interested in. AlphaFold solved the difficult scientific problem of protein folding, but it was “just mechanical”, spitting out the conformations of proteins the same way a traditional computer program spits out the digits of pi. Apparently the youth have all fallen in love with AI girlfriends and boyfriends on character.ai, but this only proves that the youth are horny and gullible.
Like ELIZA making conversation, Deep Blue playing chess, or GPT-4 writing poetry, all of this is boring.
I can’t even say this is wrong. We wouldn’t have wanted to update to “okay, we’ve solved intelligence” after ELIZA “treated” its first “patient”. And we don’t want to live in fear that GPT-4 has turned evil just because it makes up fake journal references. But it sure does make it hard to draw a red line.
Google

Google is a recurring brand in the Astral Codex Ten archive, appearing 15 times across 15 issues between March 25, 2021 and March 03, 2026. The archive places it in contexts such as "Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores"; "Apple and Google both blocked Parler from their phones"; "The highest return on investment stock of all time hasn't been Google". It most often appears alongside Google, Twitter, US.

Article page
Google
Mention count
15
Issue count
15
First seen
March 25, 2021
Last seen
March 03, 2026
March 25, 2021 · Original source
Earlier this year, Amazon, Apple, and Google simultaneously decided to block access to Parler on their app stores. A lot of libertarians objected that it was pretty scary that corporations have so much power to restrict speech they don't like, and a lot of anti-libertarians made fun of them: this is just corporations making their own decisions about their corporate property! Isn't that what you libertarians want?
But other fields have higher entry barriers than cars do. Apple and Google both blocked Parler from their phones. But these are the only two major smartphone companies. It would probably take at least a decade to set up another one, and although I think there's some demand, I'm not sure that demand can coordinate itself into a phone company that doesn't do this kind of thing.
April 19, 2021 · Original source
For a dose of cold water, see Investing in Technological Revolutions by Ben Felix. Remember, it's not how much a sector grows that makes it a good investment so much as how much it grows relative to what you paid for it. The highest return on investment stock of all time hasn't been Google, or Apple, or Tesla, or any other tech company you can name. It's Altria (MO) the cigarette company - annual returns have averaged 20.68% for nearly 50 years. Over half a century of innovation, hype, the Space Race, hype, the IT Revolution, and hype, the best returning company was in an industry everyone knew was on its way out (tobacco) - but which was on its way out far slower than everyone expected. That meant while everyone was dumping it, you could pick up the stock for peanuts relative to how much money the company was still making, and collect decades of dividends when the money flow didn't dry up.
4: OKAY WE’RE FINALLY MAKING THIS HAPPEN. Thanks to a reader, I have a list of all 80-something non-finalists in the Book Review Contest. You can see it here: Volume One (A-R), Volume Two (S-W) (we exceeded Google Docs’ puny character limit, so it’s split in half). Your mission, should you choose to accept it, is to read some number of them (even one is okay!) and then vote using this form. Please choose a random one to read each time, or select the one that looks most interesting to you, but don’t start from the beginning - if we have 5000 votes for the ones beginning with “A” and none for the ones beginning with “W”, that breaks the whole point. Choose a random one and vote on it with the form. If you read 50, you can either save them all up for one form, or send 50 forms, either way is okay (note that the form asks for your email so I can investigate potential voting irregularities; I won’t share this with anyone else). At the end, I’ll average all the ratings I have for each book, and declare the top-rated runners-up to be new finalists (in addition to the finalists I’ve already chosen). If you have questions about any of this, or you can’t access any of the relevant pages, please comment below.
EDIT: If you can’t get the Google Docs file to load, here’s PDFs of Volume 1 and Volume 2.
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
August 26, 2022 · Original source
Extra Info For Meetup Organizers: 1. If you’re the host, bring a sign that says “ACX MEETUP” and prop it up somewhere (or otherwise be identifiable). 2. Bring blank labels and pens for nametags. 3. Have people type their name and email address in a spreadsheet or in a Google Form (accessed via a bit.ly link or QR code), so you can start a mailing list to make organizing future meetups easier. 4. If it’s the first meetup, people are probably just going to want to talk, and if you try to organize some kind of “fun” “event” it’ll probably just be annoying. 5. It’s easier to schedule a followup meetup while you’re having the first, compared to trying to do it later on by email. 6. In case people want to get to know each other better outside the meetup, you might want to mention reciprocity.io, the rationalist friend-finder/dating site. 7. If you didn’t make a LessWrong event for your meetup, the LessWrong team did it for you using the email address you gave here. To claim your event, log into LW (or create an account) using that email address, or message the LW team on Intercom (chat button in the bottom right corner of lesswrong.com).
VIENNA, AUSTRIA Contact: Manuel, manuel[dot]turonian[at]gmail[dot]com Time: Saturday, September 10, 2:00 PM Location: Wiener Stadtpark at the Strauss Monument; will have an ACX Meetup sign. Coordinates: 8FWR693H+GP2 Event link(s): LessWrong Group info: Rationality Vienna is a group of about 30 people who meet once a month in person or via Zoom. You can join our Facebook group. Notes: We may want to shift to an indoor location depending on weather and the local Covid numbers. BRUSSELS, BELGIUM Contact: Bruno D, bruno[dot]astral[dot]codex[at]gmail[dot]com Time: Sunday, September 18, 4:00 PM Location: Guingette Henri, George Henri parc Coordinates: 9F26RCWC+84 Event link(s): LessWrong SOFIA, BULGARIA Contact: Anastasia, sofia[dot]acx[dot]meetup[at]gmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Shade Garden (Сенчестата градинка; part of Borisova garden) Coordinates: 8GJ5M8GW+J9 Event link(s): LessWrong Group info: Sofia ACX started with last year's Meetups Everywhere round. We have Serious Meetups once per month at which we discuss a blog post, a short story, or a book (for instance, The Scout Mindset, The Money Illusion, The Metropolitan Man); and sporadic non-serious social meetups that mostly include getting dinner, going on a walk, watching a film, or playing board games. Attendance hovers around 6-8 people out of a pool of 13. People get invited to the Discord server after they've attended at least one in-person meetup. ZAGREB, CROATIA Contact: DJStern, dorian[dot]sternvukotic[at]gmail[dot]com Time: Saturday, September 3, 6:00 PM Location: Krivi Put Coordinates: 8FQQRX38+V6W Event link(s): LessWrong Group info: Croatian LessWrong active group communicates mainly through a Telegram group, we meetup semi regularly, approx once a month. The group is mostly social, and the meetups are not structured (sometimes we all just meet at a random party) Notes: Send me an Email and I will add you to a Telegram group where everything (active) LessWrong Croatia/Zagreb happens LIMASSOL, CYPRUS Contact: Arseniy, runescape[at]list[dot]ru, @anchorheld (Telegram / Instagram) Time: Saturday, September 3, 12:00 PM Location: By the Municipal Zoo Coordinates: 8G6MM3M3+Q6 Event link(s): LessWrong Notes: Please hit me up on Mail, Telegram, or Instagram if you're actually going PRAGUE, CZECH REPUBLIC Contact: Jiri Nadvornik, jiri[dot]nadvornik[at]efektivni-altruismus[dot]cz Time: Thursday, October 6, 6:00 PM Location: Garden of Dharmasala Teahouse Coordinates: 9F2P3CRW+FP7 Event link(s): LessWrong, Facebook event COPENHAGEN, DENMARK Contact: Søren Elverlin, soeren[dot]elverlin[at]gmail[dot]com Time: Saturday, September 24, 3:00 PM Location: Rundholtsvej 10, 2300 København S Coordinates: 9F7JMH38+GFP Event link(s): LessWrong, Facebook event, Meetup.com Notes: Please RSVP on LessWrong TALLINN, ESTONIA Contact: Andrew W, andrew_n_west[at]yahoo[dot]co[dot]uk Time: Monday, September 26, 7:00 PM Location: St Vitus, Tallinn. I don't know if anyone will turn up, but I'll be wearing a suit, a beard, and a book. Coordinates: 9GF6CPRH+MQ Event link(s): LessWrong HELSINKI, FINLAND Contact: Joe Nash, joenash499[at]gmail[dot]com Time: Saturday, September 3, 4:00 PM Location: Restaurant Töölönranta, Helsinginkatu 56 Coordinates: 9GG65WMJ+2J Event link(s): LessWrong Group info: LessWrong group FONTAINEBLEAU, FRANCE Contact: Ebrahim Akbari, ea[dot]akbari[at]gmail[dot]com Time: Saturday, September 10, 6:00 PM Location: Glasgow bar, Fontainebleau Coordinates: 8FW4CP32+J8 Event link(s): LessWrong PARIS, FRANCE Contact: Olivier, w20l2qtf[at]mailer[dot]me, We have a Discord and a matrix server (both servers are bridged together) Time: Friday, September 23, 6:00 PM Location: In the jardin du carrousel, next to jardin des Tuileries Coordinates: 8FW4V86J+GH Event link(s): LessWrong Group info: Regular meetups organized via discord or the newsletter every 3 months with around 20 people. Notes: We have a mailing list if you are interested in future meetups. Please don't hesitate to send me an email to RSVP that you're coming to help gauge the interest. TOULOUSE, FRANCE Contact: Alfonso, barsom[dot]maelwys[at]gmail[dot]com Time: Saturday, October 8, 7:00 PM Location: Bar 'Le Biergarten' (60 Gd Rue Saint-Michel, 31400 Toulouse). We'll be sitting at a table with an ACX MEETUP sign on it. Coordinates: 8FM3HCQW+9H Event link(s): LessWrong Notes: Please RSVP by email TBILISI, GEORGIA Contact: Evgenia Karunus, lakesare[at]gmail[dot]com, https://twitter.com/lakesare Time: Saturday, September 17, 7:00 PM Location: Coffee Place Coordinates: 8HH6MRQ2+WH Event link(s): LessWrong AACHEN, GERMANY Contact: Jörn, acx[at]j[dot]stoehler[dot]eu Time: Tuesday, September 27, 7:00 PM Location: Chico Mendes Coordinates: 9F28Q3HJ+9Q Event link(s): LessWrong Notes: Please RSVP here so I can reserve the right number of tables. BERLIN, GERMANY Contact: Ruben Arslan, ssc[at]alphabattle[dot]xyz Time: Sunday, October 2, 2:00 PM Location: Südplateau Fritz-Schloss-Park Coordinates: 9F4MG9H4+4X Event link(s): LessWrong, Google Calendar Notes: Please RSVP on LessWrong. I'll bring some beverages. COLOGNE, GERMANY Contact: Marcel Müller, marcel_mueller[at]mail[dot]de Time: Saturday, October 8, 5:00 PM Location: Marienweg 43, 50858 Köln, private venue, just ring the bell or follow the sign. Coordinates: 9F28WRMX+96H Event link(s): LessWrong Group info: LW / ACX / Rationalist meetup group. Monthly, mostly social meetups. Other activities welcome. Unless noted otherwise we will meet at Marienweg 43 in 50858 Cologne on the 2nd Saturday of each month at 5 pm. Please email me to be added to our mailing list where deviations will be posted. Caution! September Meetup will be at a different venue! Notes: If you read this you are welcome. Our Covid rules are still in effect: You must be tested negative on the same day. Self tests will be available at the meetup. If there is any problem, like you do not find us or I did not see your mail, call me +491788862254. FREIBURG IM BREISGAU, GERMANY Contact: Omar, info[at]rationality-freiburg[dot]de Time: Friday, October 14, 6:00 PM Location: FlexRooms, Salzstr. 1, 79098 Freiburg. We will carry a cardboard sign saying “Rationality Freiburg”. Coordinates: 8FV9XVV2+V56 Event link(s): LessWrong, Meetup.com, Website Group info: The group started in May 2022 and before the summer break we had five meetups with 4-11 people attending. Every two weeks seems like a good rhythm, but nothing is set in stone. So far we always read something beforehand and then discussed it, as well as trying some practical exercises such as TAPs and Personal Calibration. Afterwards we went to have dinner and continued talking about everything and anything for hours. Everything is new and flexible, so come and help us improve! Notes: We have a Signal messenger group and ask you to attend a meetup once to be able to join. HAMBURG, GERMANY Contact: Gunnar Zarncke, g[dot]zarncke[at]gmail[dot]com Time: Saturday, September 17, 5:00 PM Location: Kleine Wallanlagen on the lawn near Memorial Holstenglacis. Look for pink blankets; I will also have an ACX sign. Here is an Open Street Map link which also shows the short-cut tunnel from the subway station. Coordinates: 9F5FHX4H+RXC Event link(s): LessWrongLessWrong Notes: Please RSVP on LessWrong KARLSRUHE, GERMANY Contact: Marcus Wilhelm, mail[at]marcuswilhelm[dot]de Time: Saturday, September 24, 3:00 PM Location: Botanischer Garten Karlsruhe Coordinates: 8FXC2C72+85X Event link(s): LessWrong Group info: We meet weekly, alternating offline and online, see our LessWrong page KASSEL, HESSEN, GERMANY Contact: Tobias, Sphinxfire[at]outlook[dot]de Time: Saturday, September 10, 2:00 PM Location: Friedrichsplatz, to the left of the DocumentaHall Coordinates: 9F3F8F6X+R6 Event link(s): LessWrong Group info: Telegram group Notes: Please join the Telegram group if you are interested in coming. It will be helpful for coordinating something beyond 'let's just see who shows up and take it from there', plus, it will also make me feel a lot better on a purely subjective level if I know beforehand that at least one other person is interested. If you prefer the surprise factor of 'knowing as little as possible about who you're going to meet', you can also just write me via E-mail, of course. LEIPZIG, GERMANY Contact: Gunther Forderung, notavailable[at]riseup[dot]net Time: Tuesday, October 4, 6:00 PM Location: In the Lene-Voigt-Park, in the secluded area opposite of the swings Coordinates: 9F3J8CM2+PF Event link(s): LessWrong TÜBINGEN, GERMANY Contact: Emma, emma[dot]tuebingen[at]gmail[dot]com Time: Sunday, October 23, 6:00 PM Location: The ACX/SSC meetup and dinner (with vegan options) will be on October 23rd at the Annette Kade dormitory (Mohlstraße 44, 8FWFG3H5+XR). If you’d like to attend, please write me an email, and I’ll send you an invitation to our WhatsApp group. Coordinates: 8FWFG3H5+XR Event link(s): LessWrong Notes: Please email me to get my phone number. If a lot of people are out of town for the holidays and can't come we could meet on, say, October 1st. I would like to know how many people to expect. ATHENS, GREECE Contact: Spyros, spyros[dot]dovas[at]gmail[dot]com Time: Monday, September 5, 7:00 PM Location: On the plaza in front of the National Library Coordinates: 8G95WMQR+WRP Event link(s): LessWrong, Meetup.com Group info: We have organized 2 events so far, fall and spring, we just sit around and discuss. We have a Whatsapp group that hasn't picked up momentum yet. Notes: Please RSVP on LessWrong or Meetup.com BUDAPEST, HUNGARY Contact: Tim Underwood, timunderwood9[at]gmail[dot]com, WhatsApp 19513120591 Time: Sunday, September 11, 2:00 PM Location: Champs Sziget bar on Margit Sziget, near the front. I'll have a big hardcover copy in Hungarian of a book by Richard Dawkins. Coordinates: 8FVXG2CW+2H Event link(s): LessWrong Group info: We've been meeting in Budapest for two years now, with our first meeting being the 2020 ACX meetups everywhere. We meet about once a month, and usually we have two articles that are suggested reading that we discuss. CORK, IRELAND Contact: Mikey, Godojhana[at]gmail[dot]com Time: Thursday, September 29, 6:00 PM Location: If sunny: The Lough. If not, then the game arcade on the parade Coordinates: 9C3HVGQ7+JQ Event link(s): LessWrong DUBLIN, IRELAND Contact: Lucius, lucius[at]bushnaq[dot]de, LessWrong profile Time: Sunday, October 2, 12:30 PM Location: Clement & Pekoe, William Street South, Dublin 2. We'll be sitting inside, and there'll be a sign with ACX written on it on the table Coordinates: 9C5M8PRP+JV Event link(s): LessWrong Group info: LessWrong FOLIGNO, ITALY Contact: Mauro, orfino[at]yandex[dot]com, LW profile, Telegram Time: Saturday, September 24, 5:00 PM Location: Parco dei Canapé, at the open air cafe, ask the barista Coordinates: 8FJJXP22+HC Event link(s): LessWrong Notes: Please RSVP on LessWrong so I know how much food to get. No kids please. MILANO, ITALY Contact: Raffaele, raffa[dot]mauro[at]gmail[dot]com Time: Friday, September 16, 6:30 PM Location: Viale Luigi Majno, 18, 20129 Milano MI - Primo Ventures / T8P, IInd floor. Coordinates: 8FQFF6C4+9C Event link(s): LessWrong Group info: We meet once per month. The group started in May 2022. Notes: Please RSVP by email by the 1st of September PADOVA, ITALY Contact: Carlo, carlo[dot]martinucci[at]gmail[dot]com Time: Saturday, October 1, 3:30 PM Location: Prato della Valle, fountain in the middle. I'll be carrying a sign with ACX MEETUP on it :) Coordinates: 8FQH9VXG+9J Event link(s): LessWrong Notes: We'll probably find a bar to have a hot chocolate or tea or something :) PISA, ITALY Contact: Raffaele, raffaelesalvia[at]alice[dot]it Time: Saturday, October 22, 5:00 PM Location: We will meet in Piazza dei Cavalieri, near the steps of Palazzo della Carovana Coordinates: 8FMGPC92+R44 Event link(s): LessWrong ROMA, ITALY Contact: Grigorio, greghero12[at]gmail[dot]com, Facebook, +393920366026 Time: Saturday, October 8, 6:00 PM Location: We'll be around Gardenie metro station, at the benches, and I will be wearing a red shirt and sitting on top of the station to be seen Coordinates: 8FHJVHP9+8F Event link(s): LessWrong Group info: We meet around 20-25 times a year but it is asymmetrical, focused in summer, Christmas and Easter. We discuss opinions, engage in circling, play games where we spot logical fallacies and biases by attacking our members ideological weakpoints and formalize some debating stances. Occasionally we find the willpower to devote meetups in steelmanning and understanding the outgroup (roughly 4-5 times a year) Notes: If you are into ACX enough to see this post, I believe we have enough common ground to be worth meeting each other. Aren't you curious who else is within this niche community in Rome? Come on, take a leap of faith. P.S. Would be nice if you sent me a message in WhatsApp with your name and probability of attendance, but I love walk-ins just fine. No space limit after all ;-) RIGA, LATVIA Contact: Andis, cerulean[dot]lemniscate[at]protonmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Bastejkalns (on top of the hill) Coordinates: 9G86X426+Q5Q Event link(s): LessWrong AMSTERDAM, NETHERLANDS Contact: Pierre, pierreavdb[at]gmail[dot]com Time: Saturday, September 10, 3:00 PM Location: Kanarie Klub (Bellamyplein 51, 1053 AT Amsterdam) Coordinates: 9F469V89+W4 Event link(s): LessWrong Group info: The rationality community is growing in the Netherlands, and we're now planning on having monthly meetups! Join the Rationality NL Discord server. Notes: Please RSVP on LessWrong so I can plan a different venue if needed DELFT, NETHERLANDS Contact: Pierre Bongrand, bongrand[dot]pierre[at]gmail[dot]com, 0033620644013 (Whatsapp/Telegram/Signal) Time: Thursday, September 22, 6:30 PM Location: Delftse Hout Beach, on the grass, in the center of the beach, I will be wearing a red T-shirt and carrying a sign with ACX MEETUP on it. Coordinates: 9F4629FG+66 Event link(s): LessWrong HATTEM, NETHERLANDS Contact: Shoshannah, shos[dot]rationality[at]gmail[dot]com, Discord: Dark#0849 Time: Saturday, October 8, 2:00 PM Location: Lijsterbeslaan 6, Hattem Coordinates: 9F48F378+PR Event link(s): LessWrong, Facebook event Group info: We support and coordinate groups across the country, including everything from social meetups to structured events and applied rationality. The intention is to connect all Dutch rationalists and rationalists in the Netherlands. We also discuss rationality topics online and coordinate events on our Discord server. Notes: Feel free to bring kids. Ours will be there :) Also, please park 't Heem if you are coming by car. It's a 2 minute walk to our house. HELMOND, NETHERLANDS Contact: Rutger, silvery[dot]swift[at]protonmail[dot]com Time: Saturday, September 17, 3:00 PM Location: De Motte (On top of the hill). Nearest road is Palladio. Coordinates: 9F37FMC5+VR Event link(s): LessWrong THE HAGUE, NETHERLANDS Contact: Kristof Redei, acxmeetup[at]kristof[dot]me Time: Wednesday, September 14, 6:00 PM Location: Paleistuin, Prinsessewal, 2513 EE Den Haag, Netherlands. We'll have a picnic blanket with an ACX sign on the large central field, somewhere near the playground. Coordinates: 9F4638J3+GP Event link(s): LessWrong, Facebook event Notes: Please RSVP on Facebook if possible! All ages/species welcome. If it's not outdoor weather, we'll go to The Bookstor Cafe next door as a backup. OSLO, NORWAY Contact: Hans Andreas & Jonas, acxoslomeetup[at]gmail[dot]com Time: Saturday, September 17, 1:00 PM Location: Look for the sign of Moloch at Café Billabong - Bogstadveien 53B 0366 Oslo Coordinates: 9FFGWPH7+QP Event link(s): LessWrong, Meetup.com Group info: We're hoping to do at least a quarterly meetup, but we'll base it on the turnout and enthusiasm of this event. Notes: The cafe has historically been accepting of guests' not ordering--please don't let financial reasons keep you away! GDAŃSK, POLAND Contact: Frank, frankastralcodexten[at]gmail[dot]com, Discord: frhrpr#1663 Time: Saturday, August 27, 3:00 PM Location: Next to Park Kuźniczki, opposite the train station, on the circular benches around the water pump; I will be wearing a red armband Coordinates: 9F6W9JJ4+JW Event link(s): LessWrong KRAKÓW, POLAND Contact: Mateusz Bagiński, bagginsmatthew[at]gmail[dot]com Time: Saturday, September 17, 2:30 PM Location: Celna 6/9, the office of the Optimum Pareto Foundation Coordinates: 9F2X2WVX+V2 Event link(s): LessWrong, Facebook event Group info: We meet every month, here is our Facebook group. LUBLIN, POLAND Contact: Piotr, piotrekzlublina[at]gmail[dot]com Time: Saturday, September 17, 5:00 PM Location: Między Słowami cafe, Rybna 4, Lublin Coordinates: 9G346HX8+FX Event link(s): LessWrong POZNAŃ, POLAND Contact: Ofelia Kerr, ofel[dot]kerr[at]gmail[dot]com, Discord: ofelia#0001 Time: Saturday, October 8, 6:00 PM Location: Van Gogh Pub, Żydowska 12, 61-761. I'll most likely be on the ground floor and I'll have an ACX sign. Coordinates: 9F4RCW5P+X3F Event link(s): LessWrong WARSAW, POLAND Contact: Michał, rationalwarsaw[at]gmail[dot]com Time: Sunday, September 4, 6:00 PM Location: Południk Zero, Wilcza 25 Coordinates: 9G4362G8+2V Event link(s): LessWrong, Meetup.com Group info: The community of Warsaw LessWrong/SSC/ACX/etc. readers is active for over 8 years now. We're trying to organise regular monthly meetups. You can join our Facebook group or Meetup.com. LISBOA, PORTUGAL Contact: Luís Campos, luis[dot]filipe[dot]lcampos[at]gmail[dot]com Time: Saturday, September 10, 3:00 PM Location: Jardim Amália Rodrigues, close to Linha d'Água cafe, in the top of a hill, below a bunch of trees Coordinates: 8CCGPRJW+V8 Event link(s): LessWrong Group info: We've been meeting every month for around 1 year. Get in contact if you want to participate in the WhatsApp group. :) BUCHAREST, ROMANIA Contact: Tony, skyrimtracer[at]gmail[dot]com Time: Sunday, October 16, 3:00 PM Location: Plaza România Mall, Bd. Timișoara 26 - food court Coordinates: 8GP8C2HM+9X Event link(s): LessWrong Notes: Please RSVP by email CLUJ-NAPOCA, ROMANIA Contact: Marius Pop, pop[dot]marius[at]gmail[dot]com Time: Saturday, September 3, 11:00 AM Location: Deva Host, Strada Deva 1-7 Coordinates: 8GR5QH8F+MW Event link(s): LessWrong BELGRADE, SERBIA Contact: Ivica Bogosavljevic, ibogosavljevic[at]gmail[dot]com, Viber +381 65 3473 433 Time: Monday, September 12, 6:00 PM Location: Pool Cafe on Prve pruge Coordinates: 8GP2RCP7+G7 Event link(s): LessWrong Notes: Please RSVP on my Viber number, so I know how big the room we need. BRATISLAVA, SLOVAKIA Contact: Viliam, viliam[at]bur[dot]sk Time: Saturday, September 10, 3:00 PM Location: Medická záhrada, by the fountain Coordinates: 8FWV44X9+XW8 Event link(s): LessWrong Notes: I will post an announcement on LessWrong later. In case of rain, a new meeting place nearby will be announced there. LJUBLJANA, SLOVENIA Contact: Demjan Vester, demjan[dot]vester[at]gmail[dot]com Time: Wednesday, September 14, 6:00 PM Location: Probably Lili Novy bar, near modern gallery and park Tivoli Coordinates: 8FRP3F3X+6V Event link(s): LessWrong, Meetup.com Group info: We meet about 0.7 times a month. Notes: Please RSVP because last time we just barely got a place big enough. BARCELONA, SPAIN Contact: Alfonso, alfonso[dot]martinez[at]upf[dot]edu, WhatsApp +34693846738 Time: Sunday, October 2, 5:30 PM Location: Parc de la Ciutadella, by the Lion Catcher statue; I'll have an ACX sign Coordinates: 8FH495QP+96 Event link(s): LessWrong Notes: The idea is to sit on the grass; bring a foulard along for your comfort, or a foldable chair if preferred. Don't worry about the language: English, Spanish, Catalan, we'll find a way. MADRID, SPAIN Contact: Jaime, jaimesevillamolina[at]gmail[dot]com Time: Saturday, September 10, 5:00 PM Location: Teatro de títeres del Parque del Retiro. We'll be on the stands with an ACX sign Coordinates: 8CGRC897+F8C Event link(s): LessWrong Group info: We are an EA / rationality group, we've been active for around 5 years but have less in-person activity since the pandemic started. We have a WhatsApp group and a channel in the Spanish-speaking EA Slack. SEVILLA, SPAIN Contact: Edu, edur[dot]acx[at]gmail[dot]com Time: Saturday, September 10, 8:00 PM Location: Parque de María Luisa. I'll be on the grass behind the Museum of Popular Arts and Traditions. I'll be the guy next to an ACX sign, a white wooden chair, and a cardboard ukulele with a tiny cardboard hat on it. Coordinates: 8C9P92F6+3RG Event link(s): LessWrong GOTHENBURG, SWEDEN Contact: Joacim, joacimj[at]gmail[dot]com Time: Saturday, September 24, 3:00 PM Location: Condeco Fredsgatan. I'll have a stack of three books on my table. Coordinates: 9F9HPX4C+39G Event link(s): LessWrong, Facebook event STOCKHOLM, SWEDEN Contact: Sal, niktonick[at]gmail[dot]com, Telegram Time: Sunday, September 25, 3:00 PM Location: Humlegården, Karlavägen. We will meet near blue gazebo, I will have 'ACX meetup' sign. Coordinates: 9FFW83RF+3M5 Group info: Facebook group BERN, SWITZERLAND Contact: Daniel, dd14214+acx[at]gmail[dot]com Time: Sunday, October 2, 4:00 PM Location: Grosse Schanze, at the statue in front of the main uni building, heading to the Pittaria if it's cold or raining Coordinates: 8FR9XC2Q+4G Event link(s): LessWrong GENEVA, SWITZERLAND Contact: Eric, eric[dot]c[dot]p[dot]meier[at]gmail[dot]com Time: Sunday, September 11, 4:00 PM Location: Park de la Grange, just towards the lake below Villa de la grange Coordinates: 8FR86548+J4 Event link(s): LessWrong Group info: We have a small persistent group who has tried to meet up once a month since last years Meetup. Notes: Feel free to bring other people you think would be interested! ZURICH, SWITZERLAND Contact: MB, acxzurich[at]proton[dot]me Time: Saturday, September 24, 3:00 PM Location: TBD Event link(s): LessWrong ISTANBUL, TURKEY Contact: J, jinai[dot]jyap[at]gmail[dot]com Time: Sunday, September 25, 4:00 PM Location: The House Cafe in Ortaköy. I am a young Asian woman and imagine I'll be easy to spot, but will also try to bring a sign with ACX MEETUP on it. Coordinates: 8GHF22XG+23P Event link(s): LessWrong, Partiful Group info: I do not live here; I am just digital nomading for an indefinite amount of time and would like to meet anyone who's here! Notes: Please RSVP via the Partiful link (you can RSVP as a Maybe)! BIRMINGHAM, UK Contact: Thomas Read, thomas[dot]read[dot]acx[at]gmail[dot]com Time: Saturday, September 3, 1:00 PM Location: We'll be at The Wellington, 37 Bennetts Hill, on the roof terrace if possible. I'll wear an orange shirt and have a sign saying ACX on the table. Coordinates: 9C4WF3JX+7Q Event link(s): LessWrong Notes: It's only a few minutes walk from the stations, so hopefully people can join from all over the West Midlands! BRIGHTON, UK Contact: Alan Enright, alanenright[at]protonmail[dot]com Time: Saturday, September 10, 11:00 AM Location: We'll be at the Alcampo Lounge on London Road—we will try and get a table on the raised area in front of you and to the left as you come in but will also have a little ACX sign. Coordinates: 9C2XRVM6+3X Event link(s): LessWrong, Meetup.com BRISTOL, UK Contact: Nick Lowry, bristoleffectivealtruism[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: We’ll be meeting at entrance closet to Tesco Express in the Galleries, Bristol City Centre Coordinates: 9C3VFC45+RJM Event link(s): LessWrong, Facebook event, Meetup.com Group info: Meet twice monthly for socials, more regular 'productive' meetups. Been active for 3+ years, please message for WhatsApp group CAMBRIDGE, UK Contact: Hamish Todd, hamish[dot]todd1[at]gmail[dot]com Time: Saturday, September 17, 2:00 PM Location: Bath House Pub, UPSTAIRS!! I will have a copy of Peter Singer's The Most Good You Can Do Coordinates: 9F426439+J9 Event link(s): LessWrong, Facebook event Group info: We meet on the third Saturday of every month. The group has been around almost a year and is well-attended! Notes: My phone/WhatsApp number is +44 0730 *** 3550, where the *** are replaced by the serial number of the Boeing plane whose first flight was on September 2, 1998. Email me to get on the mailing list for future events if you'd like that :) CARDIFF, WALES Contact: AF, strmnova[at]gmail[dot]com Time: Friday, September 16, 5:00 PM Location: Little Man Coffee (note new location!) Coordinates: 9C3RFRHH+W2 Event link(s): LessWrong EDINBURGH, SCOTLAND, UK Contact: Sam, acxedinburgh[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: Pleasance Cafe. Go through the arch and the door to the cafe is on your left Coordinates: 9C7RWRW9+M8 Group info: ~Monthly meetups, often in Pleasance Cafe but have experimented with other locations. Email me to join the mailing list & WhatsApp group. LANCASTER, UK Contact: Gruffydd Gozali, gruffyddgozali[at]gmail[dot]com Time: Saturday, October 15, 3:00 PM Location: Lancaster University Library, will be on the ground floor by the tree wearing an EA shirt. Coordinates: 9C6V2657+WJR Event link(s): LessWrong LINCOLN, UK Contact: Tobias, tobias[dot]showan[at]yahoo[dot]co[dot]uk Time: Saturday, September 10, 2:00 PM Location: Nosey Parker pub, I'll bring a little paper ACX sign. Coordinates: 9C5X6C9R+XJ Event link(s): LessWrong LONDON, UK Contact: Edward Saperia, edsaperia[at]gmail[dot]com Time: Sunday, September 25, 2:00 PM Location: Newspeak House Coordinates: 9C3XGWGH+3F7 Event link(s): LessWrong, Facebook event, Meetup.com, Eventbrite Group info: You can join our mailing list or our Meetup.com group MANCHESTER, UK Contact: Matthew Gibson, melkartmtg[at]hotmail[dot]com Time: Sunday, September 18, 11:00 AM Location: Sackville Gardens, Alan Turing Memorial Coordinates: 9C5VFQG7+MH Event link(s): LessWrong NEWCASTLE UPON TYNE, UK Contact: Joshua William, iamjoshwilliam[at]icloud[dot]com, Telegram Time: Saturday, September 3, 12:30 PM Location: Trinity Square, High Street Gosforth. You can get the bus to Gosforth from the city center just outside the famous 'Tyneside Cinema' (bus number: 30, 31, or 35 at Monument Pilgrim Street bus stop), or you can take a walk if you want to get your 'steps' in (if you'd like to do the latter, send me an email and I'll send you the directions), which takes ~60-min. Coordinates: 9C7W294H+5V Event link(s): LessWrong Group info: To my knowledge, there isn't an ACX meet up in this city, or region of the UK, though if there is a demand for a reoccurrence, I'd be happy to keep facilitating such. I'd also happily formulate a WhatsApp group if theres interest, after the meet up. Notes: We have a deli, '1901 cafe', on the square, which we can grab an immediate bite to eat at [so save some hunger if you'd like to do that]. There's a safe [and lovely] park with some benches just by the way, which, if the weather is nice, we can sit at after a bite to eat, or, otherwise, we can remain in the cafe. OXFORD, UK Contact: Sam, ssc[at]sambrown[dot]eu, There's a Signal group people can join :) contact Sam for info Time: Wednesday, October 19, 6:30 PM Location: The Star, Rectory Road, Oxford. We'll be in the beer garden round the back, with a sign ?? Coordinates: 9C3WPQX6+QP9 Event link(s): LessWrong, Facebook event, Meetup.com Group info: We run socials every months, and applied rationality workshops from time to time! Notes: Please RSVP on any of the platforms (or email) for free pizza PENRYN, CORNWALL, UK Contact: mini t, tminns[at]btinternet[dot]com Time: Saturday, August 27, 3:00 PM Location: glasney playing field and valley Coordinates: 9C2P5V8V+P9 Event link(s): LessWrong Notes: I don't mind rescheduling, or organizing another event, not many people are likely to turn up this far out of the way.
HUNTSVILLE, AL Contact: Mike, mjhouse[at]protonmail[dot]com Time: Saturday, September 3, 3:00 PM Location: Barnes & Noble – 300 The Bridge St #100, Huntsville, AL 35806. I'll be in the cafe with a sign that says ACX MEETUP on it. Coordinates: 866MP88H+53 Event link(s): LessWrong Notes: Barnes & Noble has an area for little kids. If you want to bring a service animal, that's probably fine, but I doubt they allow pets. PHOENIX, AZ Contact: Ben Morin, benjamin[dot]j[dot]morin[at]gmail[dot]com Time: Saturday, October 15, 1:00 PM Location: Thirsty Lion Pub in Tempe. I will have a table with an ACX sign. Coordinates: 8559FVVQ+6C Event link(s): LessWrong Group info: This will be our 5th meetup (started during the meetups everywhere last year). Notes: Please email if interested to be added to the email list, even if you can't make this event BELMONT, CA Contact: Moshe Z., belmont-acx[at]devskillup[dot]com Time: Sunday, September 4, 2:00 PM Location: Twin Pines Park, Picnic Tables. The table will have some sign saying 'ACX Meetup' on it. Coordinates: 849VGP8C+RRG Event link(s): LessWrong Group info: You can join the mailing list here. BERKELEY, CA Contact: Scott Time: Sunday, September 18, 1:00 PM Location: Rose Garden Inn, a rationalist event space at 2740 Telegraph Ave. Come in through the front gate on Telegraph. Coordinates: 849VVP5R+X7V Event link(s): LessWrong Group info: The Bay rationality community has a mailing list, a Discord server, and a Facebook group. There are dinner meetups every Thursday at 7 PM in the East Bay, and occasional meetups in SF and South Bay. FILLMORE, CA Contact: Ryan, wiserd[at]gmail[dot]com, Discord: Wiserd#0906 Time: Saturday, October 1st, 6:00 PM Location: It's my house. There are a bunch of plants on the porch and garbage bins in the driveway. Coordinates: 856393VX+VQ Event link(s): LessWrong Notes: Please RSVP to my email or Discord. Kids and dogs are welcome in the back yard. Full vaccinations (on the honor system) and masks required. GRASS VALLEY, CA Contact: Max Harms, raelifin[at]gmail[dot]com Time: Saturday, September 10, 2:00 PM Location: Condon Park by the prospector statue. In the case of rain we'll change the location to a residence, so RSVP to get updated! Coordinates: 84FW6W8H+C5 Event link(s): LessWrong IRVINE, CA Contact: Nick C, cohenskijanuary1[at]mail[dot]com Time: Saturday, October 1, 2:00 PM Location: University Town Center Coordinates: 8554M526+7H Event link(s): LessWrong Group info: We meet once a month at the same location. LOS ANGELES, CA Contact: Vishal Prasad (koreindian), vprasadcs[at]gmail[dot]com, Contact me on Discord. I am "Vishal" on the server. Time: Saturday, October 8, 6:30 PM Location: 11841 Wagner St., Culver City, CA 90039 Coordinates: 8553XHWM+GP Event link(s): LessWrong Group info: We meet weekly every Wednesday. We have been around for over 8 years. We discuss articles, watch movies, lift weights. We have a Discord server, a LessWrong group, and a website! Notes: Please RSVP on LessWrong so I know how much food to get. NEWPORT BEACH, CA Contact: Michael M, michaelmichalchik[at]gmail[dot]com Time: Saturday, August 27, 2:00 PM Location: Picnic tables next to 1900 Port Carlow community clubhouse. The park is verdant and pleasant and easy to access. Free street parking nearby. In case of bad weather, we have a couple of near by places to relocate to. Coordinates: 8554J48R+WCX Event link(s): LessWrong, Facebook event Group info: We will meet most Saturdays at 2pm until whenever. There will be short suggested readings and question most weeks to spur conversation, but they are optional. Each week we will ask if people have had something happen recently that surprised them or changed the way they looked at the world. Something that should or did update their priors. Participation is optional. Notes: Its a public park with tables and BBQ's so you can bring food and well behaved pets. We may regularly go on casual walks in the surrounding area. SAN DIEGO, CA Contact: Julius, julius[dot]simonelli[at]gmail[dot]com Time: Sunday, October 9, 3:00 PM Location: We will meet up in Bird Park. I will be wearing a red shirt. Coordinates: 8544PVQ8+Q7 Event link(s): LessWrong, Meetup.com Group info: Join our Discord server SAN FRANCISCO, CA Contact: Derek Pankaew, derekpankaew[at]gmail[dot]com Time: Sunday, September 18, 11:00 AM Location: We'll between in the Panhandle, between Ashbury and Masonic, with a 'ACX' sign. Coordinates: 849VQHC3+V8 Event link(s): LessWrong SAN JOSE, CA Contact: David Friedman, ddfr[at]daviddfriedman[dot]com Time: Saturday, September 17, 2:00 PM Location: 3806 Williams Rd, San Jose, CA 95117 Coordinates: 849W825J+6P Event link(s): LessWrong Group info: Before Covid we hosted every month or two. No structure, just conversation and food. We feed everyone who is still there at dinner time. We have done it once or twice since Covid. I have an email list of interested people. Notes: Kids are welcome. Please RSVP to my email so I will have a rough count of how many we are feeding. SAN MARCOS, CA Contact: Eric F., EricF14159[at]gmail[dot]com Time: Sunday, September 25, 2:00 PM Location: Hollandia Park Soccer Field. At the tables near the top parking lot. Coordinates: 85544VW4+RV Event link(s): LessWrong BOULDER, CO Contact: Josh Sacks, josh[dot]sacks+acx[at]gmail[dot]com Time: Sunday, October 16, 3:00 PM Location: 9191 Tahoe Ln, Boulder, CO 80301 Coordinates: 85GP2V96+JQ Event link(s): LessWrong Notes: Please RSVP on LessWrong so we know ~ how many people to expect! CARBONDALE, CO Contact: Nick, naj[at]njarboe[dot]com Time: Saturday, September 3, 1:00 PM Location: Sopris Park - Center covered picnic tables - blue shirt with ACX sign on table Coordinates: 85FJ9QXP+QMF Event link(s): LessWrong DENVER, CO Contact: Ian Philips, iansphilips[at]gmail[dot]com, Discord: palebone#2796 Time: Sunday, October 2, 11:00 AM Location: We'll be in the backyard patio of St. Mark's Coffee House. I'll wear a white shirt with (my brothers') baby faces on it and have a brown hat on. Coordinates: 85FQP2VP+9R Event link(s): LessWrong Group info: We meet typically 4 times a year. LAKEWOOD, CO Contact: Steven Zuber, stevenjzuber[at]gmail[dot]com Time: Wednesday, October 5, 7:00 PM Location: We meet in the clubhouse located in this townhome community: 8769 W Cornell Ave Lakewood, CO 80227 Coordinates: 85FPMW64+MW Event link(s): LessWrong, Meetup.com Group info: We meet the first Wednesday of every month. Informal, casual atmosphere with occasional presentations by people. Notes: Check the Meetup page or Facebook group for updates. FAIRFIELD, CT Contact: Justin Barclay, barclay[dot]justin[at]gmail[dot]com Time: Saturday, September 10, 10:00 AM Location: South Pine Creek Beach. I'll set up near the lifeguard stand. Coordinates: 87H84PCH+CM Event link(s): LessWrong MANCHESTER, CT Contact: Mike, park-mike[at]outlook[dot]com Time: Saturday, September 17, 5:00 PM Location: Near flagpole on top of hill Coordinates: 87H9QFFH+J7 Event link(s): LessWrong NEW HAVEN, CT Contact: RM, acx[dot]meetup[dot]nhv[at]gmail[dot]com Time: Sunday, September 18, 12:30 PM Location: Cross Campus (Yale University), New Haven, CT 06511. We'll be on the grass on the northern half of Cross Campus, closest to Sterling Memorial Library. I'll be wearing an orange shirt. Coordinates: 87H9836C+8VG Event link(s): LessWrong Notes: Feel free to bring friends! The vibe will be welcoming and relaxed, and you can stay for any amount of time. Please email me if you're thinking about coming so I can get the right number of Insomnia cookies! WASHINGTON, DC Contact: John Bennett, WashingtonDCAstralCodexTen[at]gmail[dot]com Time: Saturday, September 17, 6:00 PM Location: Froggy Bottom Pub: 2021 K Street NW, Washington, D.C. 20006 Coordinates: 87C4WX33+3J Event link(s): LessWrong, Facebook event Group info: The Washington DC ACX/SSC group has been active since the first Meetups Everywhere in 2017. We have Monthly Socials downtown, hikes, board game days, and other cultural events. We're looking to spin up more rationality Dojo-type events with nearby groups in the coming months. Notes: We've rented out the Froggy Bottom Pub for the night, dinner and soft drinks will be provided. Alcohol available for purchase if desired, but no purchases are required. Metered street parking on nearby blocks is free after 6:30. Closest Metros are Farragut West and Farragut North. CAPE CORAL / FORT MYERS, FL Contact: Shawn Spilman, shawn[dot]spilman[at]outlook[dot]com, 508 655 8123 Time: Sunday, October 2, 1:00 PM Location: 929 SW 54th Ln, Cape Coral, FL 33914 Coordinates: 76RWH224+44 Event link(s): LessWrong Notes: RSVP via email. I can be flexible about the date. GULF BREEZE / PENSACOLA, FL Contact: Christian, christian[dot]h[dot]williams[at]gmail[dot]com Time: Wednesday, October 12, 7:30 PM Location: The Bridge Bar - 33 Gulf Breeze Pkwy A, Gulf Breeze, FL 32561 Coordinates: 862J9RCF+G6 Event link(s): LessWrong Notes: Please RSVP by emailing me. Thanks! If I don't hear from anyone, I won't be there. I work for Metaculus, but promise not to talk your ear off about forecasting. (Unless you want it talked off.) MIAMI, FL Contact: Eric Magro, eric135033[at]gmail[dot]com, Discord: eric135#4943 Time: Sunday, September 11, 5:00 PM Location: Buckminster Fuller Fly's Eye Dome 140 NE 39th St #001, Miami, FL 33137 ----- Look for a paper sign on a table that says ACX MEETUP west of the dome. Coordinates: 76QXRR65+V2 Event link(s): LessWrong Group info: Miami ACX started in 2017. Our official meetup happens monthly in either Miami or Broward. There are activities happening on a weekly basis from Miami to Palm Beach. We have a Facebook group, Discord server, and Meetup.com group. ORLANDO, FL Contact: Noah Topper, noah[dot]topper[at]gmail[dot]com Time: Friday, September 16, 7:00 PM Location: 4000 Central Florida Blvd, Orlando, FL. We'll be meeting up at UCF's pavilion near Garages A and I. I'll have a pretty ACX Meetup sign. Coordinates: 76WWJQ2X+82 Event link(s): LessWrong Group info: We try to meet up once a month, so far they've just been casual social meetups with natural discussions of rationality topics. Here's our Discord link :) Notes: RSVPs on LessWrong would be greatly appreciated. :) TALLAHASSEE, FL Contact: JF, jf19o[at]fsu[dot]edu Time: Monday, August 29, 2:00 PM Location: Landis, FSU. I will be wearing a black shirt Coordinates: 862QCPR3+PX Event link(s): LessWrong ATHENS, GA Contact: Dallon, knox[dot]dallon[dot]a[at]gmail[dot]com, Discord: leonard#4208 Time: Saturday, October 15, 3:00 PM Location: Hendershots on Prince Avenue Coordinates: 865RXJ68+2W Event link(s): LessWrong Notes: I might bring some board games ATLANTA, GA Contact: Steve French, steve[at]digitaltoolfactory[dot]net Time: Saturday, September 17, 2:00 PM Location: Bold Monk Brewing - 1737 Ellsworth Industrial Blvd NW suite d-1 · Atlanta, GA (upstairs – look for the ACX Atlanta sign) Coordinates: 865QRH2F+V8 Event link(s): LessWrong, Meetup.com Group info: We've been in existence for four years – we have a dedicated crew and a very active Slack group Notes: Please RSVP on LessWrong or Meetup.com HONOLULU, HI Contact: Matt Popovich, mattpopovich[at]outlook[dot]com Time: Saturday, September 3, 4:00 PM Location: We'll meet at Magic Island at Ala Moana Beach Park, 1201 Ala Moana Blvd, Honolulu, HI 96814. From the parking lot, walk along the left side of the peninsula out toward Magic Island Lagoon. We're usually near the end of the peninsula, somewhere around the bathroom building. Look for the large 'ACX' sign. Coordinates: 73H475M3+JP Event link(s): LessWrong, Meetup.com Group info: Honolulu Rationality hosts discussion meetups about twice a month in Ala Moana Beach Park. Check us out on our website BOISE, ID Contact: Julia and John, jae[dot]miomu[at]gmail[dot]com Time: Friday, October 7, 6:00 PM Location: Old Timer's Shelter in Ann Morrison Park. I will have an ACX sign. Coordinates: 85M5JQ6P+96 Event link(s): LessWrong Notes: Please RSVP and feel free to bring kids. CHAMPAIGN-URBANA, IL Contact: Ben, cu[dot]acx[dot]meetups[at]gmail[dot]com Time: Friday, September 9, 7:00 PM Location: Siebel Center for Computer Science, Room 4403 Coordinates: 86GH4Q7G+H8F Event link(s): LessWrong Group info: Discord server Notes: RSVPs are appreciated but not at all required. You can RSVP by email or by pinging me in the Discord server. Suggested entrance is the East side of the building (see Coordinates) - we'll try to make sure at least that door is unlocked, but if it isn't then ping us on email or Discord. CHICAGO, IL Contact: Todd, info[at]chicagorationality[dot]com, https://chicagorationality.com/ Time: Sunday, September 18, 1:00 PM Location: Grant Park - North side of Balbo between the tracks and Columbus Coordinates: 86HJV9FH+84 Event link(s): LessWrong Group info: Chicago Rationality does a monthly discussion meetup (typically the first Saturday of the month) and a monthly social meetup (typically the third weekend of the month) Notes: Sign up for our email list to be notified of future meetups EVANSTON, IL Contact: Uzair, uzairq93[at]gmail[dot]com Time: Saturday, October 1, 7:00 PM Location: 626 Church Street, Evanston IL 60201 Coordinates: 86JJ28X9+5WQ Event link(s): LessWrong Notes: The venue is a pub but it's really more of a restaurant, big long tables available so space should be fine and non drinkers shouldn't feel too out of place. BLOOMINGTON, IN Contact: Avery, acxbloomington[at]fastmail[dot]com Time: Sunday, October 16, 2:00 PM Location: Switchyard Park. Will be at one of the tables near the Rogers Street parking lot. I will bring a cardboard sign that says “ACX”. Coordinates: 86FM4FX6+4Q Event link(s): LessWrong Group info: We met last year for Meetups Everywhere and it was fun! Here's a link to our Discord. Notes: You can RSVP via Discord or email, but you are encouraged to show up even if you did not RSVP! WEST LAFAYETTE, IN Contact: NR, mapreader4[at]gmail[dot]com Time: Saturday, September 17, 1:00 PM Location: 1275 1st Street, West Lafayette, IN 47906. We'll be in the south of the Earhart Hall lobby (not the dining court) near the piano, and I will be wearing a green shirt and carrying a sign with ACX MEETUP on it. Coordinates: 86GMC3GG+728 Event link(s): LessWrong LEXINGTON, KY Contact: Nathan, nwculley[at]gmail[dot]com Time: Saturday, September 3, 7:00 PM Location: Blue Stallion Brewing. 610 W. 3rd St., Lexington, KY 40508. We will have a sign indicating we are the ACX meetup. Coordinates: 86CQ3F4X+VF Event link(s): LessWrong Group info: We meet 1-2 times a month to talk about ACX, books, memes, etc., often over drinks and board games. NEW ORLEANS, LA Contact: Blake, blake[at]philosophers[dot]group Time: Sunday, September 4, 11:11 AM Location: Petite Clouet Cafe. Look for the group with an iPad that has a People’s Pint sticker. Coordinates: 76XFXX73+8R Event link(s): LessWrong Group info: Website Notes: Hybrid in-person and online, video link sent weekly. Email for the link. BOSTON, MA Contact: Robi Rahman, robirahman94[at]gmail[dot]com, 7039818526 Time: Saturday, September 10, 5:00 PM Location: Boston Common, at the Parkman Bandstand gazebo Coordinates: 87JC9W3M+PR Event link(s): LessWrong, Facebook event Group info: Mailing list, Facebook group, Meetup.com Notes: We'll be providing food at the meetup, and giving out free books related to ACX, rationality, and effective altruism. Email the hosts if you'd like a particular book or you have any dietary restrictions. Our group is also doing a tour of the JFK Presidential Library on September 9, you’re welcome to join! NORTHAMPTON, MA Contact: Alex, alex[at]alexliebowitz[dot]com Time: Friday, September 9, 6:00 PM Location: The Deck, 125A Pleasant St., Northampton MA 01096. The official address is bizarre and inaccurate; it's the outdoor dining part of a group of bars & restaurants in a former rail station... a whole block away from Pleasant St. The simplest way to get to The Deck is to enter The Platform, one of the other restaurants, by its street entrance around 36 Strong Ave., here (make sure to look at street view). Go inside and ask them to show you to The Deck. We'll have a sign. Coordinates: 87J9899F+H7H Event link(s): LessWrong, Facebook event Group info: We started in the 2018 Meetups Everywhere and is still going strong. We aim to meet about once every two weeks. At most meetups we get about 5-7 people out of a rotation of 15-20; Meetups Everywhere and other special events tend to bring in a few more than usual. We're a totally social meetup with no 'format' or suggested readings. Although it's not rare for us to touch on ACX articles and related topics, the conversation varies wildly, and you are welcome even if you're the most occasional ACX reader. Notes: We have a (not very active) Discord where you can DM me or post on a public channel. I'm most responsive by email. There is a small chance we'll have to change the location to somewhere else in Northampton. Please check the Less Wrong or Facebook posts on or after August 26 to get the final word on location. BALTIMORE, MD Contact: Rivka, rivka[at]adrusi[dot]com Time: Sunday, September 11, 7:00 PM Location: UMBC outside of the Performing Arts and Humanities Building, on the north side. I will have a sign that says ACX meetup. Parking is free on the weekends. Edit: Rain is forecasted; if it’s raining, we will be inside of the Performing Arts building, on the ground floor just inside the entrance. Coordinates: 87F5774P+53 Event link(s): LessWrong Group info: We meet Sundays at 7pm — half are in person and half are virtual. Notes: There will be pizza and drinks DETROIT, MI Contact: Matt Arnold, matt[dot]mattarn[at]gmail[dot]com Time: Tuesday, September 20, 7:00 PM Location: Tenacity Craft, 8517 2nd Ave, Detroit, MI 48202 Coordinates: 86JR9WG9+R6 Event link(s): LessWrong MINNEAPOLIS, MN Contact: Timothy, tmbond[at]gmail[dot]com Time: Saturday, September 10, 1:00 PM Location: Meet at the picnic tables near the southeast corner of Powderhorn Park - the ones by the parking lot. I will be wearing a green Google t-shirt and have a sign that says ACX. Coordinates: 86P8WPRW+76 Event link(s): LessWrong Notes: I will bring some snacks (but not a full lunch, so eat before or bring something if you'll be that hungry). Please RSVP on LessWrong. KANSAS CITY, MO Contact: Alex, alex[dot]hedtke[at]gmail[dot]com Time: Friday, September 16, 6:30 PM Location: We will be in the courtyard above Whole Foods (which is also an apartment complex). You can enter through the apartment lobby, located on Oak Street. We will have runners shepherding people from the entrance up to the courtyard. Coordinates: 86F72CM8+RR Event link(s): LessWrong, Meetup.com SAINT LOUIS, MO Contact: JohnBuridan, littlejohnburidan[at]gmail[dot]com Time: Saturday, October 8, 1:00 PM Location: Lily Pond Shelter, Tower Grove Park, St. Louis Coordinates: 86CFJP4R+XV Event link(s): LessWrong Notes: BYOB WEST PLAINS, MO Contact: Liam, liamhession[at]gmail[dot]com Time: Saturday, September 17, 12:00 PM Location: 10/40 Coffee, 24 Court Square, West Plains, MO Coordinates: 868CP4HW+CV Event link(s): LessWrong Notes: Hoping to get anyone from around the Ozark region DURHAM, NC Contact: Will Jarvis, willdjarvis[at]gmail[dot]com Time: Thursday, September 8, 7:30 PM Location: Ponysaurus Brewing Company, 219 Hood St, Durham Coordinates: 8773X4Q3+QW Event link(s): LessWrong Group info: We meet weekly! We also have a Discord LAKEWOOD, NJ Contact: Ben L, mywebdev3[at]gmail[dot]com Time: Saturday, October 29, 8:30 PM Location: TBD Event link(s): LessWrong MORRISTOWN, NJ Contact: Matt, matt[dot]brooks[at]impactmarkets[dot]io, Discord: Matt B#0216 Time: Saturday, October 1, 2:00 PM Location: 10 N Park Pl, Morristown, NJ 07960 (at the center of the Morristown Green) Coordinates: 87G7QGW9+RJ Event link(s): LessWrong Group info: This is the first meetup, come be a founding member of the Northern NJ ACX/EA/LW group! PRINCETON, NJ Contact: Danny K, dskumpf[at]gmail[dot]com Time: Saturday, October 1, 3:00 PM Location: Palmer Square, Princeton, NJ 08540. On the green right outside The Bent Spoon and Rojo's Roastary, near the big tree. I'll have some sort of ACX Meetup sign! Coordinates: 87G7982Q+2CP Event link(s): LessWrong LAS VEGAS, NV Contact: Jonathan Ray, ray[dot]jonathan[dot]w[at]gmail[dot]com Time: Sunday, September 11, 11:45 AM Location: At El Segundo Sol restaurant with giant ACX MEETUP signs Coordinates: 85864RHJ+3H Event link(s): LessWrong, Facebook event Group info: We meet regularly and mostly just socialize. We have a new Discord server. RENO, NV Contact: Steven, stevenl451[at]gmail[dot]com, Discord: Steeven#7407 Time: Friday, September 2, 5:30 PM Location: We'll be in Crissie Caughlin Park, near the tables and the swing set Coordinates: 85F2G46W+FG Event link(s): LessWrong Notes: Feel free to bring kids/dogs and please RSVP on LessWrong if you are going BUFFALO, NY Contact: George Herold, ggherold[at]gmail[dot]com Time: Sunday, September 11, 1:00 PM Location: 932 Welch Rd. Java Center, NY 14082 Coordinates: 87J3W467+8P Notes: Last-minute location change! LONG ISLAND, NY Contact: Gabe, gabeaweil[at]gmail[dot]com Time: Thursday, October 27, 7:00 PM Location: Whales Tale in Northport Coordinates: 87G8VJRW+99 Event link(s): LessWrong NEW YORK CITY, NY Contact: Jasmine, jasminermj[at]gmail[dot]com Time: Sunday, September 11, 4:00 PM Location: Pavillion @ Rockefeller Park, Warren St / River Terrace Coordinates: 87G7PX9M+4J3 Event link(s): LessWrong Group info: OBNYC has a Discord and a Google Group; the Google Group is the main mailing list we use for events NEWBURGH, NY Contact: Pedro David Bonilla, proportionatetoevidence[at]gmail[dot]com, Cell 8452001681 Time: Saturday, September 24, 10:00 AM Location: Perkins Restaurant & Bakery, 1421 NY-300, Newburgh, NY 12550 Coordinates: 87H7GWCH+GF Event link(s): LessWrong ROCHESTER, NY Contact: Skivverus, skivverus[at]gmail[dot]com, Discord: Skivverus#5915 Time: Saturday, October 8, 1:00 PM Location: 4870 Culver Road; will be wearing a polo shirt, jeans, and glasses, and may or may not have figured out a sign due to just getting back from honeymoon. Look for a pair of parrots, one white, one green with a yellow/orange head. Coordinates: 87M46FM6+Q5P Event link(s): LessWrong Notes: Venue very near amusement park; non-bathroom, non-parking amenities are therefore available but not free. Plan accordingly. Not particularly attached to specific location named, just happen to live reasonably close to there; alternative suggestions acceptable. Canadian visitors also welcome should your logistics permit; airport transportation available. RSVP via Discord preferred, but email will also work. CLEVELAND, OH Contact: Jack Zhang, LukeZhao9[at]protonmail[dot]com Time: Saturday, September 24, 1:00 PM Location: Picnic tables at Wade Oval (university circle) Coordinates: 86HWG96Q+GC5 Event link(s): LessWrong COLUMBUS, OH Contact: Daniel, daniel[dot]m[dot]adamiak[at]gmail[dot]com Time: Saturday, September 17, 3:00 PM Location: Jeffrey Park - Clinton Shelter. I will be wearing a red shirt. Coordinates: 86FVX3C3+QF Event link(s): LessWrong Group info: We meet once a month. We discuss EA, AI and other two letter initialisms. Occasionally we go for walks in local grottos and nature trails. Notes: Email me if you want to be added to the mailing list to receive any updates or future invites. RSVPing is appreciated. TOLEDO, OH Contact: Scout, scout[dot]sivar[at]gmail[dot]com Time: Saturday, September 10, 12:00 PM Location: Black Kite Coffee Coordinates: 86HRMCCV+9R Event link(s): LessWrong OKLAHOMA CITY, OK Contact: bean, battleshipbean[at]gmail[dot]com Time: Sunday, October 9, 1:00 PM Location: Edmond Public Library/Shannon Miller Park. I will be wearing a hat that says USS Iowa on it. Coordinates: 8674MG3C+MW Event link(s): LessWrong Group info: Had four people last year and a good time, moved to Edmond because a lot of us are up here. ALBANY, OR Contact: Kenan (he/him), kbitikofer[at]gmail[dot]com Time: Saturday, October 1, 2:00 PM Location: Bowman Park, Albany, Oregon. In or near the shelter. I will wear a bright red shirt and carry a sign with ACX MEETUP on it. Coordinates: 84PRJWR7+XC6 Event link(s): LessWrong CORVALLIS, OR Contact: Ethan Ashkie, ethanashkie[at]gmail[dot]com Time: Wednesday, September 7, 6:00 PM Location: Common Fields, in the reserved outdoor seating near the entrance Coordinates: 84PRHP5P+VQ Event link(s): LessWrong EUGENE, OR Contact: Ben Smith, benjsmith[at]gmail[dot]com Time: Wednesday, August 31, 7:00 PM Location: The Barn Light, 924 Willamette St, Eugene 97401 Coordinates: 84PR2WX4+VV Event link(s): LessWrong Notes: Please RSVP on LessWrong so I know how much pizza to get, but if you forget, don't worry about it, we want you to come along anyway PORTLAND, OR Contact: Sam F Celarek, support[at]pearcommunity[dot]com, 513-432-3310, Discord: Sam Celarek#2845 Time: Friday, September 9, 5:00 PM Location: 205 NW 4th Ave Coordinates: 84QVG8FG+V4 Event link(s): LessWrong, Meetup.com Group info: Portland Effective Altruism and Rationality is very active. We have book clubs, bi-weekly AI safety meet-ups, bi-weekly topical meet-ups, bi-weekly socials, and have an active Discord. Notes: We would prefer you RSVP on Meetup.com a week beforehand so that we can get the right amount of food! HARRISBURG, PA Contact: Phil, acxharrisburg[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: Ever Grain Brewing Co, 4444 Carlisle Pike, Camp Hill, PA 17011 - We will be sitting at one of the picnic tables outside with an ACX MEETUP sign Coordinates: 87G562QQ+8P Event link(s): LessWrong Group info: Small monthly meetup group based out of Harrisburg - celebrating 1 year of actuality! You can see more of our events on LessWrong. INDIANA, PA Contact: Eric, ericindianapa[at]gmail[dot]com, 717-256-2717 Time: Saturday, September 24, 11:00 AM Location: Caffè Amadeus in downtown Indiana, PA. I will have a sign with 'ACX Meetup' on one of the tables. Coordinates: 87G2JRFX+48 Event link(s): LessWrong Notes: Please RSVP via email or text message so I know how many to expect. PHILADELPHIA, PA Contact: Wes and Diana, rationalphilly[at]gmail[dot]com Time: Thursday, September 22, 6:30 PM Location: The Philadelphia Ethical Society, 1906 Rittenhouse Square. The meeting room is in the basement, look for the signs. Coordinates: 87F6WRXG+FQ Event link(s): LessWrong Group info: We tend to meet in downtown Philly on the last Thursday of the month. We're aiming to make the Ethical Society our new steady location. We have many links: Discord, Google Calendar, Facebook, Meetup, Google Group Notes: We'll be ordering food from a local restaurant, so no need to eat first. BYOB PITTSBURGH, PA Contact: Justin, pghacx[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: Westinghouse Shelter @ Schenley Park (W Circuit Rd near Schenley Dr). We have the outdoor shelter reserved, so light rain shouldn't be a problem, but in the event of extreme weather, we may relocate indoors (our default 'contingency indoor location' is Crazy Mocha Coffee on 2100 Murray Ave in Squirrel Hill). Coordinates: 87G2C3Q4+773 Event link(s): LessWrong Group info: We meet monthly-ish for general discussion and chit-chat, email me if you'd like to be notified of future meetups. STATE COLLEGE, PA Contact: John Slow, auk480[at]psu[dot]edu Time: Thursday, September 8, 5:00 PM Location: Old Main. I will be carrying an ACX meetup sign. Coordinates: 87G4Q4WP+HV Event link(s): LessWrong SAN JUAN, PUERTO RICO Contact: Dan Gelfarb, danielgelfarb[at]gmail[dot]com Time: Saturday, September 10, 1:00 PM Location: Lote 23, back corner under the tents. I will be wearing a blue shirt with a sign that says ACX meetup on it. Coordinates: 77CMCWVM+W32 Event link(s): LessWrong PROVIDENCE, RI Contact: James Bailey, feanor1600[at]gmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Prospect Terrace park, to the right of the Roger Williams statue Coordinates: 87HCRHJV+24 Event link(s): LessWrong SIOUX FALLS, SD Contact: S. C., villainsplus[at]protonmail[dot]com Time: Sunday, October 2, 5:00 PM Location: 410 E 26th St, Sioux Falls, SD 57105 - the pavillion on the west side of McKennan Park, or the tables just south of it if I can't book it. I'll be the guy with the grill. Coordinates: 86M5G7JH+W57 Event link(s): LessWrong MEMPHIS, TN Contact: Michael, michael[at]postlibertarian[dot]com Time: Monday, September 5, 1:00 PM Location: French Truck Coffee at Crosstown Concourse, Central Atrium 1350 Concourse Ave, Memphis, TN 38104. We will be at one of the many tables near French Truck Coffee and I will have a sign that says ACX MEETUP. Coordinates: 867F5X2P+QHC Event link(s): LessWrong Group info: We meet about every month or so. We've been around since 2019 but only regularly since mid 2021 due to the pandemic. We have a Discord server. NASHVILLE, TN Contact: Ellen, enwiegand[at]gmail[dot]com Time: Saturday, October 1, 11:00 AM Location: OneCity Nashville (8 City Blvd, Nashville, TN 37209), next to the volleyball courts. I'll have a pink ballcap that says SPINSTER on it. Coordinates: 868M552H+XW Event link(s): LessWrong AUSTIN, TX Contact: Silas Barta, sbarta[at]gmail[dot]com Time: Saturday, October 8, 12:00 PM Location: 4001 N Lamar, Austin Texas, park by Central Market near stone tables and tents Coordinates: 86248746+8C Event link(s): LessWrong Group info: Austin LessWrong has a weekly focused discussion, a weekly social mixer, a weekly online book club, and a monthly movie night. Been around since 2011. Notes: Location may change as we are talking to other venues BRYAN/COLLEGE STATION, TX Contact: Kenny, easwaran[at]gmail[dot]com Time: Friday, September 9, 5:00 PM Location: Back patio of Torchy's Tacos at Texas and New Main. I'll have a yellow umbrella and pinkish/purple hair Coordinates: JMFC+4J Event link(s): LessWrong DALLAS, TX Contact: Ethan Morse, ethan[dot]morse97[at]gmail[dot]com, Discord: ethanmorse#5255 Time: Sunday, September 11, 12:00 PM Location: Union, 3705 Cedar Springs Rd, Dallas, TX 75219. We'll be in the upstairs conference room. Coordinates: 8645R55R+9M9 Event link(s): LessWrong Notes: Please RSVP on LessWrong so I know how much food to get HOUSTON, TX Contact: Eric Magro, eric135033[at]gmail[dot]com Time: Sunday, September 18, 4:00 PM Location: Empire Cafe, 1732 Westheimer Rd, Houston, TX 77098 ---- Look for a table with an ACX MEETUP sign. Coordinates: 76X6PHVW+5H Event link(s): LessWrong Group info: There are meetups every week. We have a Discord and a Facebook group. WACO, TX Contact: Mike, BaylorACX[at]gmail[dot]com Time: Saturday, October 1, 1:00 PM Location: Cameron Park, picnic tables next to Jacob's Ladder Coordinates: 8634HVG2+V9 Event link(s): LessWrong Notes: Please email me if you're thinking about attending! Would love to start an ACX community here :) SALT LAKE CITY, UT Contact: Ross Richey (aka Jeremiah), wearenotsaved[at]gmail[dot]com Time: Saturday, October 8, 3:00 PM Location: Liberty Park near the ChargePoint stations Coordinates: 85GCP4WF+VJ Event link(s): LessWrong Group info: We meet every other month, we do book clubs and movie nights as well. Notes: Will be outdoors. If the weather looks bad, email event organizer to check on location. CHARLOTTESVILLE, VA Contact: RL, effectivealtruismatuva[at]gmail[dot]com Time: Sunday, September 4, 5:00 PM Location: 12 Rotunda Drive Charlottesville, VA 22903 - We’ll meet at the picnic tables across the street from The Virginian. There will be an ACX sign. Coordinates: 87C32FPX+3H4 Event link(s): LessWrong LYNCHBURG, VA Contact: Craig, craigbdaniel[at]gmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Three Roads Brewing - I will be wearing a purple t-shirt and will place an ""ACX"" card on the table Coordinates: 8792CV65+5G NORFOLK, VA Contact: Willa, walambert[at]pm[dot]me Time: Sunday, September 18, 4:00 PM Location: Pagoda & Oriental Garden, 265 W Tazewell St, Norfolk, VA 23510. I will be wearing a bright green shirt, will have a large green & yellow hat on, and will have a sign with ACX Meetup on it. Coordinates: 8785RPX4+W3 Event link(s): LessWrong, Facebook event Group info: Hi! Virginia Rationalists was co-founded in Norfolk VA earlier this year by Willa & Yitzi with the goal of growing a thriving ACX / LW / EA community in our city & the state of Virginia. We meet every week at Fair Grounds cafe on Wednesday evenings from 5-7:30pm Eastern Time. We have a Discord server and a Twitter. RESTON, VA Contact: James, jrbalch333[at]gmail[dot]com Time: Saturday, September 24, 1:30 PM Location: The matchbox at 1900 Reston Station Blvd, Reston, VA 20190 on the 1st floor of the giant Google building. I'll be holding a copy of Sapiens. Coordinates: 87C4WMX6+9X Event link(s): LessWrong Notes: Email me to be added to the WhatsApp group RICHMOND, VA Contact: Cedar, cedar[dot]ren+acxmeetup[at]gmail[dot]com, @Cedar at this Discord server Time: Saturday, October 1, 2:30 PM Location: Richmond Public Libraries, West End Branch 5420 Patterson Ave, Richmond, VA 23226 Coordinates: 8794HFHQ+3G Event link(s): LessWrong Notes: Please RSVP on LessWrong & optionally reach out to me on Discord to introduce yourself! BURLINGTON, VT Contact: Forrest, lucidobservor[at]gmail[dot]com Time: Saturday, September 10, 2:00 PM Location: Battery Park, at the benches in the south-western corner of the park, near the cannons facing the lake. I will have an 'ACX Meetup' sign. Coordinates: 87P8FQJH+8P Event link(s): LessWrong BELLINGHAM, WA Contact: Alex, bellinghamrationalish[at]gmail[dot]com Time: Thursday, September 29, 5:30 PM Location: Lake Padden Park, at one of the tables near the lake by the dog park. If it's rainy, we'll meet in one of the two covered gazebo areas just north (right, if you're facing the lake) of the planned spot. If the forecast looks really bad (e.g. very cold), I'll post an indoor location to the Meetup.com page at least three days in advance. Coordinates: 84WVMHX3+GM Event link(s): LessWrong, Meetup.com Group info: Bellingham Rationalish discusses (in good faith!) topics in and around rationality. We usually meet the evening of the last Wednesday of each month. Our first meeting was a 2021 ACX Everywhere meetup. Notes: Please RSVP on Meetup so I have an idea how many people to expect. Kids, animals, food, beverages, etc. are all welcome. SEATTLE, WA Contact: Nikita Sokolsky, sokolx[at]gmail[dot]com Time: Sunday, October 9, 5:00 PM Location: Optimism Brewing (1158 Broadway, Seattle) Coordinates: 84VVJM7H+4Q Event link(s): LessWrong, Facebook event, Meetup.com Notes: Please RSVP on LessWrong (or FB/Meetup) for planning purposes MADISON, WI Contact: Mary Wang, mmwang[at]wisc[dot]edu Time: Saturday, September 10, 1:00 PM Location: 1022 High St. Blue house with red porches. If weather permits, we'll be in my large backyard, which has more seating now than last year. If rain, come in the side door. There will be air purifiers and open windows. Masks optional. Look for a sign at the end of the driveway that says ACX/SSC Meetup. Coordinates: 86MG3H3X+XW Event link(s): LessWrong, Facebook event Group info: We have met fortnightly in the past, but quit last year when it got too cold to meet outside. We typically have shared a meal, sat around my kitchen table and talked. Have held a Solstice celebration.
September 06, 2022 · Original source
Content is already effectively free…the ability to browse many lifetimes’ worth of art and writing using Google search – and all that for $0 – has not made the creation of new art feel spurious […]
“I’ve written a book,” an acquaintance tells me. “I don’t care,” I reply with brusque honesty. “I have all the books I want already. I just find ‘em on Google and Amazon and Goodreads.” Except of course I don’t say that, because no one ever says that, and not just out of politeness. “I’ve written a book,” an acquaintance tells me. “I don’t care,” I reply. “I have all the books I want already. The AI writes them for me.” Except of course I don’t say that. Why would I?
December 20, 2022 · Original source
when you’re not sure which of many competing experts to trust, you should trust a prediction market instead of any of them Going through these claims one by one: 3.1: Why expect all prediction markets to agree with each other? Either all prediction markets agree with each other, or you can get rich quick: Suppose prediction markets disagreed. For example, suppose the RNC ran an Official Republican Prediction Market that said there was only a 10% chance Democrats would win the next election, and a 90% chance Republicans would. And suppose the DNC ran an Official Democrat Prediction Market that made the opposite prediction: 90% chance Democrats, 10% chance Republicans. Then you could buy a share of “Democrats will win” from the Republican market for 10 cents, plus a share of “Republicans will win” from the Democrat market for 10 cents, and be guaranteed to make $1 when one party or the other wins. You have turned 20 cents into a guaranteed $1. Repeat until you are rich or the mispricing has been corrected. This is just what financial experts call “arbitrage”. You may notice that in finance, people always give specific prices for things like shares of stock, barrels of oil, or Bitcoins. People say things like “Google stock is up to $300”, but never “Google stock is up to $300 on the NYSE, but down to $200 on NASDAQ”. If that was true, people would buy it on NASDAQ, sell it on NYSE, make $100 in free money, and get rich quick. In ideal situations, arbitrage forces everybody everywhere to agree on the same price for a financial instrument. Prediction markets turn claims about truth into financial instruments in a way which forces everybody everywhere to agree on how likely the claim is to be true. 3.2: Why expect prediction markets to be hard for special interests to manipulate? Either a prediction market is not currently mispriced because of a manipulation attempt, or you can get rich quick. Argument: Suppose a prediction market was currently mispriced because of a manipulation attempt. For example, suppose there is a prediction market for whether the sun will rise tomorrow. The true probability is obviously 100%, corresponding to a cost of $1.00. But suppose some special interest who wanted to trick people into believing the sun would not rise successfully spent money to bid the market down to only 10%. This means that you can buy, for $0.10, a share which pays $1 if the sun rises tomorrow. In other words, you can dectuple your money for free. Repeat until you are rich or the mispricing has been corrected. This may sound complicated in theory, but it plays out straightforwardly in real life. As a test, I tried to manipulate the market on whether Austin Chen, founder of Manifold Markets, would be charged with a felony. There’s no reason to think he should be, so the price started at 5%. I spent $200 in Manifold’s play money bidding it up to 95%. Within an hour, other investors noticed the mispricing and corrected it back down to 5% again. 3.3: Why expect prediction markets to be free from bias? Either a prediction market is not currently mispriced because of bias, or you can get rich quick. The argument: Suppose all smart people, including you, know that there is an 80% chance that the Democrats’ economic plan will create new jobs. But suppose that Republicans, because of their partisan biases, refuse to believe it, and say there is only a 40% chance. And suppose the Republicans set up their own prediction market where they bid the price of a share down to $0.40. You can, of course, go on this prediction market, buy shares for $0.40, and double your money in expectation. Repeat until you are rich or the mispricing has been corrected. I already described how something like this happens on PredictIt (a non-ideal prediction market that you can only make a few hundred dollars in expectation by correcting), and that I do in fact make a few hundred dollars every election season. 3.4: Why should I believe a prediction market’s consensus over my own opinion? This is the same argument as “the prediction market will always be at least as accurate as the top expert” only with you in the place of the top expert. Either prediction markets are at least as smart as you are, or you can get rich quick. The argument here is the same as “at least as smart as the smartest expert” argument in 2, except replacing “the smartest expert” with “you”. But just to lay it out explicitly: Suppose you were smarter than some prediction market. Then if you disagreed with the market, usually you would be right and it would be wrong. So look for cases where you disagree with the market, buy those shares, and you will make money in expectation. Repeat until you are rich or the mispricing has been corrected. I like this because it’s a good empirical test, and one that many people have tried. If you think you’re smarter than the prediction markets, bet on them and see what happens! I think most people will find that (over the long run) they lose money, and eventually this will cure them of their delusion that they can beat the markets. A few people might find that (over the long run) they do win money, just as a few people (eg Warren Buffett) can consistently win money on the stock market. Hopefully those people will quit their day jobs and become full-time prediction market traders. They’ll become multimillionaires, and their hard work will ensure that prediction markets stay more accurate than the rest of us. 3.5: Why should I believe that a prediction market makes good decisions about which of many competing experts to trust? Suppose you accept that a prediction market will always be at least as accurate as some well-known expert (eg Nate Silver). But what if you’re not sure who the real experts are? Or what if there are many experts, all saying different things, and nobody knows who to trust? In this case, a prediction market will always be at least as good as any other source (including you) at telling good experts from bad, or at figuring out which of many good experts is the best. By this point you should be able to predict the argument, but for completeness’ sake: Suppose you were better than the prediction market at determining which of many competing experts to trust, or how to aggregate the pronouncements of many experts into a single authoritative opinion. Then if you disagreed with the market, usually you would be right and it would be wrong. So look for cases where you disagree with the market, buy those shares, and you will make money in expectation. Repeat until you are rich or the mispricing has been corrected. To ground this in a real example, suppose there is some new virus which might or might not spread to the United States. A Harvard professor of epidemiology says there’s a 70% chance it will spread, a Yale professor of epidemiology says there’s an 90% chance it will spread, and a guy in a tinfoil hat on Infowars says there’s a 0% chance it will spread because it’s all a fake government plot. If I knew nothing else about this situation, I would probably think there’s about an 80% chance the virus will spread. I trust the Harvard and Yale professors equally much, and the tinfoil hat guy not at all. Suppose I saw a prediction market that was only at 10%, because most people trusted the tinfoil hat guy. I would want to buy YES shares until the price got up to 80%, because in expectation I would octuple my money. Suppose I saw a prediction market that was only at 70%. Now I wouldn’t be sure whether the prediction market was dumber than me (believed tinfoil hat guy) or smarter than me (they know a lot about epidemiology - or about the credibility of specific experts - and have decided to trust the Harvard professor over the Yale professor). Maybe I could improve on this. If I knew things about epidemiology, I could read over both professors’ arguments and try to figure out if one was better than the other. If I knew things about academia, I could pick over both professors’ resumes and see whether the Harvard professor seemed more distinguished or had more respect in her own field than the Yale professor. In the end, I might decide the prediction market was right to price it at 70% (in which case I wouldn’t do anything), or that actually both experts seemed equally expert (in which case I might bid it up to 80%), or that actually the Yale epidemiologist was better (in which case I might bid it up to 90%). 3.5.1: Isn’t it weird to give non-experts (like prediction market investors) the final judgment in which of two experts is right? Yes, but I don’t think this is avoidable. If there were no such thing as prediction markets, and the Harvard epidemiologist said 70%, and the Yale epidemiologist said 90%, and the tinfoil hat guy said 0%, and for some reason it mattered a lot to you which of these was true - then you would still have to make that decision. If there’s some extremely authoritative source who can make the decision for you - let’s say the World Health Organization says “after reviewing all experts’ arguments, we believe that the final probability is 75%” - then great! Either: The WHO is clearly the most trustworthy source - in which case we go back to the Nate Silver situation where the prediction market should be just as accurate as it is.
Some companies have their own internal prediction markets, most famously Google. Last I checked, Google was offering their services to other companies that wanted to try the same thing, so you might want to try getting in touch with them.
June 28, 2023 · Original source
An unblockable moving status bar that switches every few seconds between different messages about the product! This is what they think the people most obsessed with blocking flashing/changing elements on websites want! This new “show a constantly-moving status bar on screen to tell you when they will change another flashing element” thing has also made it onto the front page of Bing, although luckily you can dismiss it there. I would have expected Google to resist. They haven’t. I can no longer write things on Gmail - I have to compose on Notepad and then copy-paste to the Gmail window - because they’ve made it look like this: It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
How do I get rid of the blinking “Draft Saved” message?
November 10, 2023 · Original source
Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one. There are a few different ones out there.
Scott's idea sounds kind of like Search Engine Optimization - there's thousands of websites competing for the first few Google results, and as soon as someone figures out a way to game the system, Google changes the algorithm and that game no longer works. It's an arms race between you, all your competitors, and Google.
May 07, 2024 · Original source
There definitely used to be a tech industry exception - or rather the tech industry was flagrantly violating CR hiring rules and getting away with it because it was so new and shiny and prestigious. Google's famous interview questions were thinly disguised IQ tests and other companies had similar practices. Of course the result was massive disparate impact. However, Griggs vs Duke Power Co does allow employers to use tests narrowly tailored for the job, and possibly EEOC bureaucrats could not figure out how to argue that coding-based tests like Google's are not legitimate or that hiring good software engineers is not a compelling enough business interest to set aside disparate impact requirements.
My admittedly anedotical 0.05$ as a generic office drone. *Every* white collar job I've heard of uses patently IQ test-like screening. I'm not talking about Google or Jane Street, I'm talking about big4 consultancies, mid-sized accounting firms etc. Places where productivity is not nearly high enough to justify resisting the acrimonious persecution Hanania posits, and that yet are happy to ask their applicants to submit Raven matrices or quirky plane geometry problems (the joke is even that the only thing those working there got out of grad school/MBA was prepping for the GMAT/GRE, since once hired they'll end up filling excels anyway).
I may be n=1 person, but I've heard that similar things are happening at Apple, Disney, Dreamworks, several large game studios (you would have heard of them if you were in the space, but I won't mention them, because that industry is small), Google, Facebook/Meta... I'll just stop there, but suffice it to say, this isn't everything.
May 30, 2024 · Original source
The only cities where searches for EA-related terms are prevalent enough for Google to show it are in the Bay Area and Boston…We know the spatial distribution of effective altruist ideas. We can also get IRS data on charitable giving…
Stone finds that Google Trends shows that searches for “effective altruism” concentrate most in the San Francisco Bay Area and Boston. So he’s going to see if those two cities have higher charitable giving than average, and use that as his metric of whether EAs give more to charity than other people.
I’m not going to make a big deal about Stone’s use of Google Trends, because I think he’s right that SF and Boston are the most EA cities. But taken seriously, it would suggest that Montana is the most Democratic state. Stone could potentially still object that movements aren’t supposed to gather 10,000 committed adherents and grow at 10% per year. They have to take hold of the population! Capture the minds of the masses! Convert >5% of the population of a major metropolitan area! I don’t think effective altruism has succeeded as a mass movement. But I don’t think that’s it’s main strategy - for more on this, see the articles under EA Forum tag “value of movement growth”, which explains: It may seem that, in order for the effective altruism movement to do as much good as possible, the movement should aim to grow as much as possible. However, there are risks to rapid growth that may be avoidable if we aim to grow more slowly and deliberately. For example, rapid growth could lead to a large influx of people with specific interests/priorities who slowly reorient the entire movement to focus on those interests/priorities. Aren’t movements that don’t capture the population doomed to irrelevance? I don’t think so. Effective altruism has managed to get plenty done with only 10,000 people, because they’re the right 10,000 and they’ve influenced plenty of others. Stone fails to prove that effective altruists don’t donate more than other people, because he’s used bad methodology that couldn’t prove that even if it were true. His critique could potentially evolve into an argument that effective altruism hasn’t spread massively throughout the population, but nobody ever claimed that it did. II. You might imagine that a group fixated on “effective altruism” would have a high degree of concentration of giving in a small number of areas. Indeed, EAist groups tend to be hyper-focused on one or two causes, and even big groups like Open Philanthropy or GiveWell often have focus areas of especially intense work. And yet, the list of causes EAists work on is shockingly broad for a group whose whole appeal is supposed to be re-allocating funds towards their most effective uses. Again, click the link I attached above. EAists do everything from supporting malarian bednets (seems cool), to preventing blindness-related conditions (makes sense), to distributing vaccines (okay, I’m following), to developing vaccines in partnership with for profit entities (a bit more oblique but I see where you’re going with it), to institutional/policy interventions (contestable, but there’s a philosophical case I guess), to educational programs in rich countries (sympathetic I guess but hardly the Singer-esque “save the cheapest life” vibe), to promoting kidney transplants (noble to be sure but a huge personal cost for what seems like a modest total number of utils gained), to programs to reduce the pain experienced by shrimp in agriculture (seems… uh… oblique), to lobbying efforts to prevent AI from killing us all (lol), to space flight (what?), to more nebulous “long term risk” (i.e. “pay for PhDs to write white papers”), to other even more alternatively commendable, curious, or crazy causes. My point is not to mock the sillier programs (I’ll do that later). My point is just to question on what basis so broad a range of priorities can reasonably be considered a major gain in efficiency. Is it really the case that EAists have radically shifted our public understandings of the “effectiveness” of certain kinds of “altruism”? A few responses: Technically, it’s only correct to focus on the single most important area if you have a small amount of resources relative to the total amount in the system (Open Phil has $10 billion). Otherwise, you should (for example) spend your first million funding all good shrimp welfare programs until the marginal unfunded shrimp welfare program is worse than the best vaccine program. Then you’ll fund the best vaccine program, and maybe they can absorb another $10 million until they become less valuable than the marginal kidney transplant or whatever. This sounds theoretical when I put it this way, but if you work in charity, it can quickly becomes your whole life. It’s all very nice and well to say “fund kidney transplants”, but actually there are only specific discrete kidney transplant programs, some of them are vastly better than others, and none of them scale to infinity instantaneously or smoothly. The average amount that the charities I deal with most often can absorb is between $100K and $1MM. Again, Open Phil has $10 billion. But even aside from this technical point, people disagree on really big issues. Some people think animals matter and deserve the same rights as humans. Other people don’t care about them at all. Effective altruism can’t and doesn’t claim to resolve every single ancient philosophical dispute on animal sentience or the nature of rights. It just tries to evaluate if charities are good. If you care a lot about shrimp, there’s someone at some effective altruist organization who has a strong opinion on exactly which shrimp-related charity saves shrimp most cost-effectively. But nobody (except philosophers, or whatever) can tell you whether to care about shrimp or not. This is sort of a cop-out. Effective altruism does try to get beyond “I want to donate to my local college’s sports team”. I think this is because that’s an easy question. Usually if somebody says they want to donate there, you can ask “do you really think your local college’s sports team is more important than people starving to death in Sudan?” and they’ll think for a second and say “I guess not”. Whereas if you ask the same question about humans and animals, you’ll get all kinds of answers and no amount of short prompting can solve this disagreement. I think this puts EAs in a few basins of reflective equilibrium, compared to scattered across the map. So is there some sense, as Stone suggests, that “so broad a range of priorities [can’t] reasonably be considered a major gain in efficiency”? I think if you look at donations by the set of non-effective-altruist donors, and the set of effective-altruist donors, there will be much much more variance, and different types of variance, in the non-EAs than the EAs. Here’s where most US charity money goes (source): Try spotting existential risk prevention on here. I don’t think Stone can claim that an EA version of this chart wouldn’t look phenomenally different. But then what’s left of his argument? III. Effective altruists devote absolutely enormous amounts of mental energy and research costs to program assessment, measurement of effectiveness. Those studies yield usually-conflicting results with variable effect sizes across time horizons and model specifications, and tons of different programs end up with overlapping effect estimates. That is to say, the areas where EAist style program evaluations are most compelling are areas where we don’t need them: it’s been obvious for a long time how to reduce malaria deaths, program evaluations on that front have been encouraging and marginally useful, but not gamechanging. On the other hand, in more contestable areas, EAist style program evaluations don’t really yield much clarity. It’s very rare that a program evaluation gets published finding vastly larger benefits than you’d guess from simple back-of-the-envelope guesswork, and the smaller estimates are usually because a specific intervention had first-order failure or long-run tapering, not because “actually tuberculosis isn’t that bad” or something like that. Those kinds of precise program-delivery studies are actually not an EAist specialty, but more IPA’s specialty. My second critique, then is this: there is no evidence that the toolkit and philosophical approach EAists so loudly proclaim as morally superior actually yields any clarity, or that their involvement in global efforts is net-positive vs. similar-scale donations given through near-peer organizations. The IPA mentioned here is Innovations For Poverty Action, a group that studies how to fight poverty. They’re great and do great work. But IPA doesn’t recommend top charities or direct donations. Go to their website, try to find their recommended charities. Unless I’m missing something, there are none. GiveWell does have recommended charities - including ones that they decided to recommend based on IPA’s work - and moves ~$250 million per year to them. If IPA existed, but not GiveWell, the average donor wouldn’t know where to donate, and ~$250 million per year would fail to go to charities that IPA likes. I think from the perspective of people who actually work within this ecosystem, Stone’s concern is like saying “Farms have already solved the making-food problem, so why do we need grocery stores?” (also, effective altruism funds IPA) I’m focusing on IPA here because Stone brought them up, but I think EA does more than this. I don’t think there’s an IPA for figuring out whether asteroid deflection is more cost-effective than biosecurity, whether cow welfare is more effective than chicken welfare, or figuring out which AI safety institute to donate to. I think this is because IPA is working on a really specific problem (which kinds of poverty-related interventions work) and EA is working on a different problem (what charities should vaguely utilitarian-minded people donate to?) These are closely related questions but they’re not the same question - which is why, for example, IPA does (great) research into consumer protection, something EA doesn’t consider comparatively high-impact. And I’m still focusing on donation to charity, again because it’s what Stone brought up, but EA does other things - like incubating charities, or building networks that affect policy. IV. Let’s skip farm animal welfare for a second and look at the next few: Global Aid, “Effective Altruism,” potential AI risks, biosecurity, and global catastrophic risk. These are all definitely disproportionate areas of EAist interest. If you google these topics, you will find a wildly disproportionate number of people who are EAist, or have sex at EAist orgies, or are the friends of people who have sex at EAist orgies. These really are some of the unique social features of EAism. And they largely amount to subsidizing white collar worker wages. I’m sorry but there’s no other way to slice it: these are all jobs largely aimed at giving money to researchers, PhD-holders, university-adjacent-persons, think tanks, etc. That may be fine stuff, but the whole pitch of effective altruism is that it’s supposed to bypass a lot of the conventional nonprofit bureaucracy and its parasitism and just give money to effective charities. But as EAism as matured into a truly unique social movement, it is creating its own bureaucracy of researchers, think tanks, bureaucrats… the very things it critiqued. Suppose an EA organization funded a cancer researcher to study some new drug, and that new drug was a perfect universal cure for cancer. Would Stone reject this donation as somehow impure, because it went to a cancer researcher (a white-collar PhD holder)? EA gives hundreds of millions of dollars directly to malaria treatments that go to the poorest people in the world. It’s also one the main funders of GiveDirectly, a charity that has given money ($750 million so far) directly to the poorest people in the world. But in addition to giving out bednets directly, it sometimes funds malaria vaccines. In addition to giving to poor Africans, it also funds the people who do the studies to see whether giving to poor Africans works. Some of those are white-collar workers. EA has never been about critiquing the existence of researchers and think tanks. In fact, this is part of the story of EA’s founding. In 2007, the only charity evaluators accessible by normal people rated charities entirely on how much overhead they had - whether the money went to white-collar people or to sympathetic poor recipients. EAs weren’t the first to point out that this was a very weak way of evaluating charities. But they were the first to make the argument at scale and bring it into the public consciousness, and GiveWell (and to some degree the greater EA movement) were founded on the principle of “what if there was a charity evaluator that did better than just calculate overhead?” In accordance with this history, if you look on Giving What We Can’s List Of Misconceptions About Effective Altruism, their #1 Misconception about about charity evaluation is that “looking at a charity’s overhead costs is key to evaluating its effectiveness”. This is another part of my argument that EA is more than just IPA++. For years, the state of the art for charity evaluators was “grade them by how much overhead they had”. IPA and all the great people working on evidence-based charity at the time didn’t solve that problem - people either used CharityNavigator or did their own research. GiveWell did solve that problem, and that success sparked a broader movement to come up with a philosophy of charity that could solve more problems. Many individuals have always had good philosophies of charity, but I think EA was a step change in doing it at scale and trying to build useful tools / a community around it. V. You could of course say AI risk is a super big issue. I’m open to that! But surely the solution to AI risk is to invest in some drone-delivered bombs and geospatial data on computing centers! The idea that the primary solution here is going to be blog posts, white papers, podcasts, and even lobbying is just insane. If you are serious about ruinous AI risk, you cannot possibly tell me that the strategy pursued here is optimal vs. say waiting until a time when workers have all gone home and blowing up a bunch of data centers and corporate offices. In particular terrorism as a strategy may be efficient since explosives are rather cheap. To be clear I do not support a strategy of terrorism!!!! But I am questioning why AI-riskers don’t. Logically, they should. I think if you have to write in bold with four exclamation points at the end that you’re not explicitly advocating terrorism, you should step back and think about your assumptions further. So: Should people who worry about global warming bomb coal plants? Should people who worry that Trump is going to destroy American democracy bomb the Republican National Convention? Should people who worry about fertility collapse and underpopulation bomb abortion clinics? EAs aren’t the only group who think there are deeply important causes. But for some reason people who can think about other problems in Near Mode go crazy when they start thinking about EA. (Eliezer Yudkowsky has sometimes been accused of wanting to bomb data centers, but he supports international regulations backed by military force - his model is things like Israel bombing Iraq’s nuclear program in the context of global norms limiting nuclear proliferation - not lone wolves. As far as I know, all EAs are united against this kind of thing.) There are three reasons not to bomb coal plants/data centers/etc. The first is that bombing things is morally wrong. I take this one pretty seriously. The second is that terrorism doesn’t work. Imagine that someone actually tried to bomb a data center. First of all, I don’t have statistics but I assume 99% of terrorists get caught at the “your collaborator is an undercover fed” stage. Another 99% get eliminated at the “blown up by poor bomb hygiene and/or a spam text message” stage. And okay, 1/10,000 will destroy a datacenter, and then what? Google tells me there are 10,978 data centers in the world. After one successful attack, the other 10,977 will get better security. Probably many of these are in China or some other country that’s not trivial for an American to import high explosives into. The third is that - did I say terrorism didn’t work? I mean it massively massively backfires. Hamas tried terrorism, they frankly did a much better job than we would, and now 52% of the buildings in their entire country have been turned to rubble. Osama bin Laden tried terrorism, also did an impressive job, and the US took over the whole country that had supported him, then took over an unrelated country that seemed like the kinds of guys who might support him, then spent ten years hunting him down and killing him and everyone he had ever associated with. One f@#king time, a handful of EAs tried promoting their agenda by committing some crimes which were much less bad than terrorism. Along with all the direct suffering they caused, they destroyed EA’s reputation and political influence, drove thousands of people away from the movement, and everything they did remains a giant pit of shame that we’re still in the process of trying to climb our way out of. Not to bang the same drum again and again, but this is why EA needs to be a coherent philosophy and not just IPA++. You need some kind of theory of what kinds of activism are acceptable and effective, or else people will come up with morally repugnant and incredibly idiotic plans that will definitely backfire and destroy everything you thought you were fighting for. EA hasn’t always been the best at avoiding this failure mode, but at least we manage to outdo our critics. VI. Stone moves on to animal welfare: It’s important to grasp that [caring about animals] is, in evolutionary terms, an error in our programming. The mechanisms involved are entirely about intra-human dynamics (or, some argue, may also be about recognizing the signs of vulnerable prey animals or enabling better hunting). Yes humans have had domestic animals for quite a long time, but our sympathetic responses are far older than that. We developed accidental sympathies for animals and then we made friends with dogs, not vice versa. Again, this is part of why I think it’s useful to have people who think about philosophy, and not just people who do RCTs. People having kids of their own instead of donating to sperm banks is in some sense an “error” in our evolutionary program. The program just wanted us to reproduce; instead we got a bunch of weird proxy goals like “actually loving kids for their own sake”. Art is another error - I assume we were evolutionarily programmed to care about beauty because, I don’t know, flowers indicate good hunting grounds or something, not because evolution wanted us to paint beautiful pictures. Anyone who cares about a future they will never experience, or about people on far off continents who they’ll never meet, is in some sense succumbing to “errors” in their evolutionary programming. Stone describes the original mechanisms as “about intra-human dynamics”, but this is cope - they’re about intra-tribal dynamics. Plenty of cultures have been completely happy to enslave, kill, and murder people outside their tribes, and nothing in their evolutionary mechanism has told them not to. Does Stone think this, too, is an error? At some point you’ve got to go beyond evolutionary programming and decide what kind of person you want to be. I want to be the kind of person who cares about my family, about beauty, about people on other continents, and - yes - about animal suffering. This is the reflective equilibrium I’ve landed in after considering all the drives and desires within me, filtering it through my ability to use Reason, and imagining having to justify myself to whatever God may or may not exist. Stone suggests EAs don’t have answers to a lot of the basic questions around this. I can recommend him various posts like Axiology, Morality, Law, the super-old Consequentialism FAQ, and The Gift We Give To Tomorrow, but I think they’ll only address about half of his questions. The other half of the answers have to come from intuition, common sense, and moral conservatism. This isn’t embarrassing. Logicians have discovered many fine and helpful logical principles, but can’t 100% answer the problem of skepticism - you can fill in some of the internal links in the chain, but the beginning and end stay shrouded in mystery. This doesn’t mean you can ignore the logical principles we do know. It just means that life is a combination of formally-reasonable and not-formally-reasonable bits. You should follow the formal reason where you have it, and not freak out and collapse into Cartesian doubt where you don’t. This is how I think of morality too. Again, I really think it’s important to have a philosophy and not just a big pile of RCTs. Our critics make this point better than I ever could. They start with “all this stuff is just common sense, who needs philosophy, the RCTs basically interpret themselves”, then, in the same essay, digress into: If I wanted to do this stuff, I would try terrorism.
December 17, 2024 · Original source
2: Russia fines Google $20,000,000,000,000,000,000,000,000,000,000,000 for blocking Russian YouTube channels.
June 03, 2025 · Original source
Other (A - I)
Other (J - S)
Other (T - Z)
December 31, 2025 · Original source
A key part of the “Brooklyn Theory” is that the media industry really is a total nightmare of endless layoffs, unpaid internships, city newspapers shutting down etc as Google et al. eat all the advertising revenue. They have been in an awful recession for decades and since they have the megaphones, they can spread their misery to everyone else.
January 05, 2026 · Original source
I’m looking for a strong software or ML engineer to cofound the world’s first ‘automation-first’ AI safety lab. As a founding member of the UK’s AI Safety Institute, I saw firsthand how organisational, engineering and research bottlenecks limit humanity’s ability to build the safety tooling we need. To keep pace with AI’s rapid capability advances, we’ll need to go all-in on augmenting safety research and engineering with AI. I’m betting that a different kind of organisation - lean, flexible, relentlessly focused on automation with AI agents - can capture these gains to build at scales that would have been unimaginable a few years ago. I’ve received a generous grant from ACX to build this full-time, starting with AI evaluations. If this is something you feel should exist (no AI safety background required), reach out here or via LinkedIn.
Some people have argued that you have to find a way to join an AI company, because AI company employees will form the new ruling class, with everyone else as serfs. I disagree. The main thing an AI company employee has that you don’t is AI company stock. But you can buy stock in Google, you may soon be able to buy stock in OpenAI and Anthropic, and even if not, you can get indirect exposure to these companies via stock in Amazon and Microsoft. I don’t recommend putting all your money in these stocks. But there’s no fundamental difference between a Google employee having 75% of their money in Google stock because they didn’t cash out their equity vs. you having 75% of your money in Google stock because you’re crazy and fail at diversification. So either put 75% of your money in Google stock or don’t (I recommend don’t), and don’t worry about how you need to join an AI company or be left out of the future oligarchy.
March 03, 2026 · Original source
Framed this way, the Pentagon’s actions sound devastating. Anthropic relies on compute to train and run its AIs. Most of this compute is in data centers owned by Amazon, Google, and Microsoft. At least Amazon and Microsoft have contracts with the US military. If they had to drop Anthropic, it would make it impossible for the company to stay a frontier AI lab.
The lawyers who weighed in seem to think that Anthropic’s interpretation of the law is correct, and Secretary Hegseth’s interpretation confused. In some situations, this might be cold comfort - how much does it help to be right about the law when the government is wrong? But in this case, it probably helps a lot. Amazon, Google, and Microsoft are all big Anthropic investors - each owns about a 10% stake - and have multi-billion dollar AI compute contracts. Together, the three tech giants must have at least $100 billion riding on Anthropic’s success. They also have good administration connections and great lobbyists, and even Hegseth isn’t stupid enough to pick fights with them all at once. So probably they send their lobbyists to have a talk with Hegseth about what the “supply chain risk” designation actually entails, Hegseth enforces the letter of the law, and Anthropic is barely affected. At least this is the story the prediction markets are going with:
GPT

GPT is a recurring brand in the Astral Codex Ten archive, appearing 12 times across 12 issues between September 12, 2022 and February 25, 2026. The archive places it in contexts such as "GPT-like models scaled up several orders of magnitude (100T parameters)"; "I have no doubt that GPTs of various sizes can simulate an 'AI' character who resists being shut down, etc"; "a few months after they came out with GPT". It most often appears alongside OpenAI, Anthropic, Claude.

Article page
GPT
Mention count
12
Issue count
12
First seen
September 12, 2022
Last seen
February 25, 2026
September 12, 2022 · Original source
At the time, I wrote: I’m not going to make the mistake of saying these problems are inherent to AI art. My guess is a slightly better language model would solve most of them…for all I know, some of the larger image models have already fixed these issues. These are the sorts of problems I expect to go away with a few months of future research. This proved controversial. Gary Marcus in particular has emphasized how challenging compositionality is for modern language and image models: @sama @gdb @Plinz @ylecun, \n\nEach of you ridiculed my recent title, but this is what the article was actually about: compositionality.\n\nYes, there are many kinds of progress in other directions. \n\nBut compositionality is at the core of intelligence. \n\nNo AGI without it. ","username":"GaryMarcus","name":"Gary Marcus","profile_image_url":"","date":"Sat Apr 09 04:34:37 +0000 2022","photos":[],"quoted_tweet":{"full_text":"Compositionality *is* the wall. \n\nEven “red cube” and “blue cube” on their own are represented unreliably; not one of ten images correctly captures the full phrasal description.\n\nThe images are beautiful, but no match for the precision of language. https://t.co/uvoXUtETwi","username":"GaryMarcus","name":"Gary Marcus"},"reply_count":0,"retweet_count":7,"like_count":54,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> And one of my commenters, Vitor, asked: Why are you so confident in this? The inability of systems like DALL-E to understand semantics in ways requiring an actual internal world model strikes me as the very heart of the issue. We can also see this exact failure mode in the language models themselves. They only produce good results when the human asks for something vague with lots of room for interpretation, like poetry or fanciful stories without much internal logic or continuity. Not to toot my own horn, but two years ago you were naively saying we'd have GPT-like models scaled up several orders of magnitude (100T parameters) right about now (https://slatestarcodex.com/2020/06/10/the-obligatory-gpt-3-post/#comment-912798). I'm registering my prediction that you're being equally naive now. Truly solving this issue seems AI-complete to me. I'm willing to bet on this (ideas on operationalization welcome). I responded to Marcus here, and I responded to Vitor by making a bet on whether AI image models could draw some compositionality-heavy pictures by 2025. The specific terms we agreed on: My proposed operationalization of this is that on June 1, 2025, if either if us can get access to the best image generating model at that time (I get to decide which), or convince someone else who has access to help us, we'll give it the following prompts: 1. A stained glass picture of a woman in a library with a raven on her shoulder with a key in its mouth 2. An oil painting of a man in a factory looking at a cat wearing a top hat 3. A digital art picture of a child riding a llama with a bell on its tail through a desert 4. A 3D render of an astronaut in space holding a fox wearing lipstick 5. Pixel art of a farmer in a cathedral holding a red basketball We generate 10 images for each prompt, just like DALL-E2 does. If at least one of the ten images has the scene correct in every particular on 3/5 prompts, I win, otherwise you do. DALL-E can’t do any of these: If I were being kind, I would give it the farmer in the cathedral. But I am being unkind, so the farmer in front of the cathedral doesn’t count. II. There are now at least four more AI image models available: Google Imagen announced May 2022.
January 03, 2023 · Original source
No direct inline source block was recovered for this mention.
March 01, 2023 · Original source
Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
And so on . . . Meanwhile, in real life, OpenAI released ChatGPT in late November, helped Microsoft launch the Bing chatbot in February, and plans to announce GPT-4 in a few months. Nobody thinks society has even partially adapted to any of these, or that alignment researchers have done more than begin to study them. The only sense in which OpenAI supports gradualism is the sense in which they’re not doing lots of research in secret, then releasing it all at once. But there are lots of better plans than either doing that, or going full-speed-ahead. So what’s OpenAI thinking? I haven’t asked them and I don’t know for sure, but I’ve heard enough debates around this that I have some guesses about the kinds of arguments they’re working off of. I think the longer versions would go something like this: The Race Argument: Bigger, better AIs will make alignment research easier. At the limit, if no AIs exist at all, then you have to do armchair speculation about what a future AI will be like and how to control it; clearly your research will go faster and work better after AIs exist. But by the same token, studying early weak AIs will be less valuable than studying later, stronger AIs. In the 1970s, alignment researchers working on industrial robot arms wouldn’t have learned anything useful. Today, alignment researchers can study how to prevent language models from saying bad words, but they can’t study how to prevent AGIs from inventing superweapons, because there aren’t any AGIs that can do that. The researchers just have to hope some of the language model insights will carry over. So all else being equal, we would prefer alignment researchers get more time to work on the later, more dangerous AIs, not the earlier, boring ones.
Reading even further between the lines - at this point it’s total guesswork - OpenAI’s corporate partner Microsoft asked them for a cool AI. OpenAI assumed Microsoft was competent - they make Windows and stuff! - and gave them a rough draft of GPT-4. Microsoft was not competent, skipped fine-tuning and many other important steps which OpenAI would not have skipped, and released it as the Bing chatbot. Bing got in trouble for threatening users, which gave OpenAI a PR headache around safety. Some savvy alignment people chose this moment to approach them with their latest ideas (is it a coincidence that Holden Karnofsky published What AI Companies Can Do Today earlier that same week?), and OpenAI decided (for a mix of selfish and altruistic reasons) to get on board - hence this document.
June 07, 2023 · Original source
No direct inline source block was recovered for this mention.
November 27, 2023 · Original source
First, GPT-4 has over 100 billion neurons (the exact number seems to be secret, but it’s somewhere up there).
A friend who understands these issues better than I warns that we shouldn’t expect to find pentagons and square anti-prisms in GPT-4. Probably GPT-4 does something incomprehensible in 1000-dimensional space. But it’s the 1000-dimensional equivalent of these pentagons and square anti-prisms, conserving neurons by turning them into dimensions and then placing concepts in the implied space.
Shouldn’t the AI be keeping the concept of God, Almighty Creator and Lord of the Universe, separate from God- as in the first half of Godzilla? Probably GPT-4 does that, but this toy AI doesn’t have enough real neurons to have enough simulated neurons / features to spare for the purpose. In fact, you can see this sort of thing change later in the paper:
March 12, 2024 · Original source
The first team is Halawi et al at Berkeley (also including Jacob Steinhardt, featured here before). They cite previous work on out-of-the-box AIs like GPT-4 or Claude. When these enter forecasting tournaments, they might beat some especially unskilled participants, but they lag behind the easiest aggregation method: “the wisdom of crowds”, ie a simple average of all forecasts. The wisdom of crowds is hard to beat - in my tournament, it scored at the 95th percentile.
Halawi fine-tunes the out-of-the-box AI (in his case, a version of GPT-4) using some of the same tricks as FutureSearch. They attach it to “news APIs” (NewsCatcher, Google News) and teach it to search them effectively and reason about the contents.
Forecasting skills of different AIs (lower is better). GPT-4 did best so they mostly used that for their system. In one part of the experiment, they use a human-written scratchpad to prompt the reasoning; in another, they fine-tune an AI on these scratchpads so it doesn’t need to use them every time. They get all these different AIs to make multiple predictions and average them together (wisdom of inner crowds - easier for AIs than humans since you can just raise the temperature!)
May 29, 2024 · Original source
No direct inline source block was recovered for this mention.
April 01, 2025 · Original source
We have recontextualized the semantic apocalypse from a one-time problem with GPT-4 to a recurrent historical pattern of technology undermining the uniqueness of art. But maybe we should zoom out further. This isn’t just about art. Technology breeds hedonic adaptation, and hedonic adaptation undermines everything.
July 08, 2025 · Original source
Not to toot my own horn, but two years ago you were naively saying we'd have GPT-like models scaled up several orders of magnitude (100T parameters) right about now (https://slatestarcodex.com/2020/06/10/the-obligatory-gpt-3-post/#comment-912798).
September 04, 2025 · Original source
Note: percentages are of total, not of each row! 29: Related: social science team proposes a three-stage model of secularization: decreased public ritual participation → decreased personal importance → decreased identification, presents apparently confirmatory data. If true, would be somewhat inconsistent with intellectual models (eg people learn about evolution and start doubting the Bible) and more consistent with institutional models (eg the government provides welfare so people no longer need to be part of a tight-knit church). 30: Navigating LLMs’ spiky intelligence profile is a constant source of delight; in any given area, it seems like almost a random draw whether they will be completely transformative or totally useless. Now Ethan Strauss reports that they are, for some reason, extraordinarily effective at teaching people golf. “I am predicting the Golf Revolution, or perhaps decline, if your perspective is that optimization tends to ruin hobbies. A sport for obsessives has been gifted the ideal tool for refinement.” 31: Claim (via nxthompson on X): “In a huge survey of young kids about phones and technology, they all say they want to be out playing in the real world. But parents don't let them out unsupervised. So they're stuck on their phones.” Interesting, but I’m nervous about social desirability bias - how many adults would say on a survey that they would rather be on their phones than playing with friends? But adults do have this choice and mostly go with the phones. 32: Steven Adler on AI psychosis. He tries to analyze ER admissions data for psychosis and finds no change. I don’t think anyone reasonable expected this to be a large enough effect to show up in ER admissions data, but there are lots of unreasonable people so I appreciate his effort. He thinks AI companies might have better data on this, and encourages them to release it. 33: Cuartetera was the greatest polo horse ever. Polo players responded in a very practical way: they cloned her, dozens of times (and it worked; the clones are also excellent). Now there is a lawsuit as different polo teams fight to get their hands on Cuartetera clones. What is the equilibrium? If the outsiders get their hands on the genetic material, do we see a world where every polo horse is a Cuartetera clone? How much is lost if nobody ever tries to breed a polo horse better than Cuartetera (since the economics might not check out if the odds of success for any given foal is too low)? H/T Gwern and Siberian Fox (on X). 34: Claim: as of 2013, India’s Agarwal caste, who make up less than 1% of the population, got 40% of the e-commerce funding. 35: Owlposting: What Happened To Pathology AI Companies? Pathology is a medical specialty. A typical task involves looking at a microscope slide full of cells and trying to determine if any of them are cancerous. This seems like a good match for AI - and for years, studies have been showing that in fact AI can equal human experts. So why isn’t it being used more? The author’s three answers: first, slide scanning is expensive and clunky, and you can’t apply AI to a slide until you digitize it. Second, it’s hard to figure out a business plan where this saves someone money and doesn’t step on the toes of big companies that can outcompete anyone they don’t like. Third, pathologists use the context of a patient’s entire clinical history when they interpret a slide, and AIs that can’t do that (either because of technical limitations or legal/privacy limitations) are at a disadvantage even if their skills specifically relating to slide-reading are better. 36: Noahpinion: Will Data Centers Crash The Economy? Suppose that AI is a bubble, either permanently (because the technology isn’t really transformative) or temporarily (because it can’t transform things quickly enough to keep up with all the dumb money pouring into it). Will the sudden write-off of data centers lead to a broader economic collapse? In 2001, the dot-com bubble harmed the tech sector, but didn’t take the rest of the economy down with it; in 2008, the subprime mortgage bubble did take the rest of the economy down with it, because it damaged banks that the whole economy relied on. The optimistic case for AI is that data center spending is mostly coming from big companies like Google and Meta that can absorb a lot of loss. The pessimistic case is that some of the money is coming from private credit, a new-ish form of finance which hasn’t really been stress-tested and whose failure modes are still poorly understood. Noah’s final verdict: the stage isn’t obviously set for a crisis yet, but there’s the potential to get there and we should consider acting (how?) early. 37: The latest Twitter talking point is that universal hepatitis B vaccination at birth is “woke”: Hep B is (aside from mother-to-child transmission) often sexually transmitted, slutty women’s children are more likely to have Hep B, so perhaps giving the vaccine to everyone (instead of testing and only giving to the children of women who test positive) is an attempt to spare slutty women the embarrassment of getting a positive test. Ruxandra Teslo provides the counterargument - Hep B tests take a while, the medical system is fragmented, and any attempt to test people and then give the vaccine inevitably leads to many positive tests falling through the cracks. Vaccinating at birth is easy and hard to screw up, the vaccine has no known side effects, and empirically child Hepatitis B rates go down (by as much as 2/3!) when countries switch from test-and-vaccinate to universal vaccination. This benefits everyone - even people who never have unprotected sex and always follow up on their medical tests - because toddlers in daycare exchange saliva copiously, and if your toddler exchanges saliva with a Hep B positive toddler they could get the disease. A funny Twitter interaction was seeing Republicans in Congress hop on the anti-slut anti-vaccination bandwagon - except for Senator Bill Cassidy (R-Louisiana), who happens to be a liver doctor, and who is still fighting the good fight. I am always nervous when a good person who I like starts engaging on Twitter, since it elevates the discourse there but also gradually turns their brain into mush - but Ruxandra has made the leap and is doing a great job not just on bio related topics but also (for example) countering Curtis Yarvin on the history of her native Romania. 38: The response to GPT-5 was confusing; most specific people who reviewed it said they were impressed (Ethan Mollick, Tyler Cowen, Nabeel Qureshi, Taelin), it performed as expected on formal benchmarks, but the overall vibes declared it a big failure. Peter Wildeford speculated that maybe there was some kind of sinister pay-to-play early access bias involved. Zvi went the other way, calling it a “reverse DeepSeek moment” (insofar as DeepSeek was a pretty average model that got glowing praise.) In the end, I agree with Peter that this was mostly a branding issue. o3 was a genuinely revolutionary model; if OpenAI had called it “GPT-5”, it would have met expectations. Instead, they called it “o3”, and called a minor incremental update a few months later “GPT-5”. Then people got mad that the exciting-sounding “GPT-5” was merely an incremental update. A secondary issue was that the router wasn’t very good, and so many queries got routed to a small version without thinking mode that was if anything a downgrade from o3. I think this tweet by Shakeel perfectly encapsulates the essence of GPT discourse in two sentences: …but maybe it’s worth asking why GPT-5 isn’t bigger than o3. Was 4.5 a failed attempt at scaling? Did it fail in a way that sort of back-handedly justifies the “lost steam” take? Does the answer depend on distinctions between pre-training scaling, post-training scaling, etc? How? 39: This month in etymology: did you know that “oy vey” is a “fully Germanic phrase” which is cognate with English “oh woe!” (h/t Wylfcen on X) 40: mRNA shows promise to be a game-changing treatment for cancer, but RFK is trying to halt research. But so far he can only starve it of money, not ban it, and the funding gap is only $500 million. Will there be enough philanthropic billionaires and private foundations to step up? Zvi points out that although there is usually a game of chicken where foundations are hesitant to touch something the government cancelled lest the government decide it can cancel everything and hope philanthropists pick up the bill, in this case there are no game theory considerations - RFK is halting it because he genuinely wants it halted, and they are thwarting him rather than playing into his hands. The only problem is that $500M is a lot of money for the private sector; a few foundations could technically afford it, but not many could afford it comfortably and still have money left over for the next few crises of this magnitude. I hope someone is trying to organize a coalition. 41: AI fantasy flash fiction Turing test. Eight stories about demons, four by famous fantasy authors, four by ChatGPT. After 3000 votes, AI wins: humans can't tell the difference and slightly prefer the AI stories. My own score was only 75%. But I will say that I thought Mark Lawrence's was obviously the best, I was ~100% sure it was human, and it convinced me that regardless of the official results it's still possible to write flash fiction that an AI obviously can't do. 42: “SignPro” offers customized “In This House We Believe” signs, try not to use this for evil. 43: China think tank assessment of how in control Xi is: still very in control, maybe not infinitely in control. 44: Related - did you know (h/t xlr8harder) that if you ask AI to write a science fiction story, it will very often name the protagonist “Elara Voss” (or some very close variant like Elena Voss), and this remains true across various models and versions? Related: Chelsea Voss of OpenAI is having a baby and has the opportunity to do the funniest thing. 45: “Hector (cloud) is a cumulonimbus thundercloud cluster that forms regularly nearly every afternoon on the Tiwi Islands in the Northern Territory of Australia…[he is sometimes called] Hector the Convector”. 46: British allergy sufferers who want to know the ingredients of things demand that British cosmetics stop listing their ingredients in Latin. “For example, sweet almond oil is Prunus Amygdalus Dulcis, peanut oil is Arachis Hypogaea, and wheat germ extract is Triticum Vulgare.” 47: Text-based RPG about being an NYT journalist at the Manifest prediction market conference. I make a brief appearance. 48: Study uses supposedly-random variation in doctor assignments to test whether the marginal mental health commitment is good or bad for patients, finds that it is quite bad. Freddie de Boer is violently skeptical (maybe literally so?) and makes some good points about how a single quasi-experimental study is never absolute proof. But I don’t think he quite justifies his opinion that the paper was irresponsible and should never have been published; it’s just a normal quasi-experimental study that we should nod and say “huh” at but not overweight as the culmination of all possible research that overcomes all possible priors. My prior is that the marginal commitment is pretty useless (many commitments are just “well, since this person arrived at our ED for some reason, it would look bad from a medico-legal perspective to just let them go, so let’s keep them a few days to evaluate” - and yeah, you should be upset about this) but I’m still surprised by how many outright negative (as opposed to zero) effects the researchers found. The strongest argument for negative effects is that it will make some people miss work and maybe lose their job. But this study found that commitment ~doubles the risk of near-term suicide (admittedly only from 1% to 2%), which would have been outside my confidence intervals for how bad it could be. I suspect confounding, but only on general principle, and I wouldn’t be too surprised either way. 49: This tweet is probably bait, but I found it a thought-provoking question: I think there’s a boring answer, where the law is more complex than just a single number and whatever kind of weird trafficking Epstein was doing is worse than whatever normal relationships these European laws are permitting. But assuming that there’s a substantive difference even after taking that into account, I think my answer is something like - we’ve got to divide kids from adults at some age, there’s a range of reasonable possible ages, we shouldn’t be too mad at other societies that choose different dividing lines within that range - but having decided upon the age, we’ve got to stick with it and take it seriously (in the sense of penalizing/shaming people who break it). This is more culturally relativist than I expected to find myself being, so good job to Richard for highlighting the apparent paradox. 50: Dilan Esper describes his experience as one of Hulk Hogan’s attorneys in the Gawker lawsuit (X). Parts I found interesting: none of the lawyers knew Thiel was funding the lawsuit; Gawker probably could have won if they had been slightly competent but kept "shooting themselves in the foot"; and Gawker probably could have won if they had just pixelated the private parts in the video. 51: Amazing concept and poems (link on X): I tried to see if AI could do this, and it did something that technically met the requirements but had zero artistic merit - using a lot of words like “nowhere” and “outside” in one, then separating them out to “no where” and “out side” in the other. I didn’t invest much energy in creating a clever prompt telling it not to do that, so feel free to report if you get better success. 52: New study claims consultants are actually good, at least for profits: "We find positive effects on labor productivity of 3.6% over five years, driven by modest employment reductions alongside stable or growing revenue" 53: A Polish team tries to test Peter Turchin’s equations for predicting political unrest on recent Polish history, has to make some changes but claims mostly positive results. 54: New big multi-author Substack, The Argument, trying to be a sort of center-left version of the model pioneered by The Free Press and other high-production-value ideological Substack properties. Excited to see Kelsey Piper is involved, and she starts off strong with a post on the latest round of First World basic income studies, which find few positive effects. This is surprising, because recipients didn’t waste the money on alcohol or gambling or anything - they paid down debt and got useful goods. Still, it didn’t even affect things that should have been obvious, like stress level. It’s not even clear that amounts of money large enough to help with rent made homeless people more likely to get houses! Matt Bruenig criticizes the article, accusing Kelsey’s studies of being downstream of Perry Preschool style dreams that exactly the right welfare program will have massively compounding effects that cut poverty out at the root and turn everyone into elite human capital; he thinks giving people money won’t do this, but it will increase equality and give the poor better lives. I assume he’s not a strong hereditarian, but his argument makes even more sense from that perspective, and I’ve certainly criticized dumb outcome measures like infant brain waves which we have only tenuous reasons to think are related to anything we care about. But Kelsey reasonably responds that the outcome measures she’s talking about include stress level and life satisfaction. To defuse this critique, Bruenig either has to argue that our construct “life satisfaction” doesn’t really measure whether someone’s life is satisfactory, or else claim that giving poor people satisfactory lives isn’t really what we’re going for - which I think would require more explanation on his part. There’s some further (impressively acrimonious) debate on X, but I don’t see anything that addresses my core concern. GiveDirectly, a charity involved in basic income experiments, has a presponse here; they say that some studies are positive, and that the ones that aren’t might have tried too little cash to matter, or been confounded by COVID making everything worse. They also point out that basic income is harder to study than traditional programs like giving people housing, because if you’re giving housing you can measure housing-related outcomes directly and have a pretty good chance of getting enough statistical power to find them, but since everyone spends cash on different things, the positive effects might be scattered across many different outcomes (and therefore too small to reach significance on each). Everyone involved in this debate wants to emphasize that the poor results are for First World studies only, and that studies continue to show large benefits to giving cash in the developing world. 55: Related: I was less impressed by The Argument’s first foray into housing policy, which follows an all-too-familiar pattern: Some people say they don’t like noise and disorder and try to make rules against it in their apartments.
…but maybe it’s worth asking why GPT-5 isn’t bigger than o3. Was 4.5 a failed attempt at scaling? Did it fail in a way that sort of back-handedly justifies the “lost steam” take? Does the answer depend on distinctions between pre-training scaling, post-training scaling, etc? How? 39: This month in etymology: did you know that “oy vey” is a “fully Germanic phrase” which is cognate with English “oh woe!” (h/t Wylfcen on X) 40: mRNA shows promise to be a game-changing treatment for cancer, but RFK is trying to halt research. But so far he can only starve it of money, not ban it, and the funding gap is only $500 million. Will there be enough philanthropic billionaires and private foundations to step up? Zvi points out that although there is usually a game of chicken where foundations are hesitant to touch something the government cancelled lest the government decide it can cancel everything and hope philanthropists pick up the bill, in this case there are no game theory considerations - RFK is halting it because he genuinely wants it halted, and they are thwarting him rather than playing into his hands. The only problem is that $500M is a lot of money for the private sector; a few foundations could technically afford it, but not many could afford it comfortably and still have money left over for the next few crises of this magnitude. I hope someone is trying to organize a coalition. 41: AI fantasy flash fiction Turing test. Eight stories about demons, four by famous fantasy authors, four by ChatGPT. After 3000 votes, AI wins: humans can't tell the difference and slightly prefer the AI stories. My own score was only 75%. But I will say that I thought Mark Lawrence's was obviously the best, I was ~100% sure it was human, and it convinced me that regardless of the official results it's still possible to write flash fiction that an AI obviously can't do. 42: “SignPro” offers customized “In This House We Believe” signs, try not to use this for evil. 43: China think tank assessment of how in control Xi is: still very in control, maybe not infinitely in control. 44: Related - did you know (h/t xlr8harder) that if you ask AI to write a science fiction story, it will very often name the protagonist “Elara Voss” (or some very close variant like Elena Voss), and this remains true across various models and versions? Related: Chelsea Voss of OpenAI is having a baby and has the opportunity to do the funniest thing. 45: “Hector (cloud) is a cumulonimbus thundercloud cluster that forms regularly nearly every afternoon on the Tiwi Islands in the Northern Territory of Australia…[he is sometimes called] Hector the Convector”. 46: British allergy sufferers who want to know the ingredients of things demand that British cosmetics stop listing their ingredients in Latin. “For example, sweet almond oil is Prunus Amygdalus Dulcis, peanut oil is Arachis Hypogaea, and wheat germ extract is Triticum Vulgare.” 47: Text-based RPG about being an NYT journalist at the Manifest prediction market conference. I make a brief appearance. 48: Study uses supposedly-random variation in doctor assignments to test whether the marginal mental health commitment is good or bad for patients, finds that it is quite bad. Freddie de Boer is violently skeptical (maybe literally so?) and makes some good points about how a single quasi-experimental study is never absolute proof. But I don’t think he quite justifies his opinion that the paper was irresponsible and should never have been published; it’s just a normal quasi-experimental study that we should nod and say “huh” at but not overweight as the culmination of all possible research that overcomes all possible priors. My prior is that the marginal commitment is pretty useless (many commitments are just “well, since this person arrived at our ED for some reason, it would look bad from a medico-legal perspective to just let them go, so let’s keep them a few days to evaluate” - and yeah, you should be upset about this) but I’m still surprised by how many outright negative (as opposed to zero) effects the researchers found. The strongest argument for negative effects is that it will make some people miss work and maybe lose their job. But this study found that commitment ~doubles the risk of near-term suicide (admittedly only from 1% to 2%), which would have been outside my confidence intervals for how bad it could be. I suspect confounding, but only on general principle, and I wouldn’t be too surprised either way. 49: This tweet is probably bait, but I found it a thought-provoking question: I think there’s a boring answer, where the law is more complex than just a single number and whatever kind of weird trafficking Epstein was doing is worse than whatever normal relationships these European laws are permitting. But assuming that there’s a substantive difference even after taking that into account, I think my answer is something like - we’ve got to divide kids from adults at some age, there’s a range of reasonable possible ages, we shouldn’t be too mad at other societies that choose different dividing lines within that range - but having decided upon the age, we’ve got to stick with it and take it seriously (in the sense of penalizing/shaming people who break it). This is more culturally relativist than I expected to find myself being, so good job to Richard for highlighting the apparent paradox. 50: Dilan Esper describes his experience as one of Hulk Hogan’s attorneys in the Gawker lawsuit (X). Parts I found interesting: none of the lawyers knew Thiel was funding the lawsuit; Gawker probably could have won if they had been slightly competent but kept "shooting themselves in the foot"; and Gawker probably could have won if they had just pixelated the private parts in the video. 51: Amazing concept and poems (link on X): I tried to see if AI could do this, and it did something that technically met the requirements but had zero artistic merit - using a lot of words like “nowhere” and “outside” in one, then separating them out to “no where” and “out side” in the other. I didn’t invest much energy in creating a clever prompt telling it not to do that, so feel free to report if you get better success. 52: New study claims consultants are actually good, at least for profits: "We find positive effects on labor productivity of 3.6% over five years, driven by modest employment reductions alongside stable or growing revenue" 53: A Polish team tries to test Peter Turchin’s equations for predicting political unrest on recent Polish history, has to make some changes but claims mostly positive results. 54: New big multi-author Substack, The Argument, trying to be a sort of center-left version of the model pioneered by The Free Press and other high-production-value ideological Substack properties. Excited to see Kelsey Piper is involved, and she starts off strong with a post on the latest round of First World basic income studies, which find few positive effects. This is surprising, because recipients didn’t waste the money on alcohol or gambling or anything - they paid down debt and got useful goods. Still, it didn’t even affect things that should have been obvious, like stress level. It’s not even clear that amounts of money large enough to help with rent made homeless people more likely to get houses! Matt Bruenig criticizes the article, accusing Kelsey’s studies of being downstream of Perry Preschool style dreams that exactly the right welfare program will have massively compounding effects that cut poverty out at the root and turn everyone into elite human capital; he thinks giving people money won’t do this, but it will increase equality and give the poor better lives. I assume he’s not a strong hereditarian, but his argument makes even more sense from that perspective, and I’ve certainly criticized dumb outcome measures like infant brain waves which we have only tenuous reasons to think are related to anything we care about. But Kelsey reasonably responds that the outcome measures she’s talking about include stress level and life satisfaction. To defuse this critique, Bruenig either has to argue that our construct “life satisfaction” doesn’t really measure whether someone’s life is satisfactory, or else claim that giving poor people satisfactory lives isn’t really what we’re going for - which I think would require more explanation on his part. There’s some further (impressively acrimonious) debate on X, but I don’t see anything that addresses my core concern. GiveDirectly, a charity involved in basic income experiments, has a presponse here; they say that some studies are positive, and that the ones that aren’t might have tried too little cash to matter, or been confounded by COVID making everything worse. They also point out that basic income is harder to study than traditional programs like giving people housing, because if you’re giving housing you can measure housing-related outcomes directly and have a pretty good chance of getting enough statistical power to find them, but since everyone spends cash on different things, the positive effects might be scattered across many different outcomes (and therefore too small to reach significance on each). Everyone involved in this debate wants to emphasize that the poor results are for First World studies only, and that studies continue to show large benefits to giving cash in the developing world. 55: Related: I was less impressed by The Argument’s first foray into housing policy, which follows an all-too-familiar pattern: Some people say they don’t like noise and disorder and try to make rules against it in their apartments.
November 26, 2025 · Original source
Compute: America is far ahead. We have better chips (thanks, NVIDIA) and can produce many more of them (thanks, TSMC). Our recent capex boom, where companies like Google and Microsoft spend hundreds of billions of dollars on data centers, has no Chinese equivalent. By the simplest measure - total FLOPs on each sides - we have 10x as much compute as China, and our advantage is growing every day. A 10x compute advantage corresponds to about a 1-2 year time advantage, or an 0.5 - 1 generation advantage (eg GPT-4 to GPT-5).
February 25, 2026 · Original source
No direct inline source block was recovered for this mention.
ivermectin

ivermectin is a recurring brand in the Astral Codex Ten archive, appearing 11 times across 11 issues between February 16, 2021 and January 16, 2026. The archive places it in contexts such as "treating severe COVID (with eg ivermectin, fluvoxamine)"; "Group A got low-dose ivermectin"; "The experimental group got a lot of things other than ivermectin". It most often appears alongside COVID, ivermectin, Alexandros Marinos.

Article page
ivermectin
Mention count
11
Issue count
11
First seen
February 16, 2021
Last seen
January 16, 2026
February 16, 2021 · Original source
When the fifth wave strikes in late spring/early summer, some of the population (~50%?) will be vaccinated, another part of the population (~25%?) will have had the disease already, and the rest (~25%?) will be completely vulnerable. The new strains will probably cause a limited number of mild cases among the vaccinated/resistant, and a larger number of more severe cases among the vulnerable. Either way, the presence of the larger vaccinated/resistant contingent could potentially make this less severe than previous waves. Also, we may have learned more about treating severe COVID (with eg ivermectin, fluvoxamine), which might further decrease deaths.
November 17, 2021 · Original source
But here’s my pitch: this is one of the most carefully-pored-over scientific issues of our time. Dozens of teams published studies saying ivermectin definitely worked. Then most scientists concluded it didn’t. What a great opportunity to exercise our study-analyzing muscles! To learn stuff about how science works which we can then apply to less well-traveled terrain! Sure, you read the articles saying that experts had concluded the studies were wrong. But did you really develop a gears-level understanding of what was going on? That’s what we have a chance to get here!
Any deep dive into ivermectin has to start here:
This is from ivmmeta.com, part of a sprawling empire of big professional-looking sites promoting unorthodox coronavirus treatments. I have no idea who runs it - they’ve very reasonably kept their identity secret - but my hat is off to them. Each of these study names links to a discussion page which extracts key outcomes and offers links to html and pdf versions of the full text. These same people have another 35 ivermectin studies with different inclusion criteria, subanalyses by every variable under the sun, responses and counterresponses to everyone who disagrees with them about every study, and they’ve done this for twenty-nine other controversial COVID treatments. Putting aside the question of accuracy and grading only on presentation and scale, this is the most impressive act of science communication I have ever seen. The WHO and CDC get billions of dollars in funding and neither of them has been able to communicate their perspective anywhere near as effectively. Even an atheist can appreciate a cathedral, and even an ivermectin skeptic should be able to appreciate this website. What stands out most in this image (their studies on early treatment only; there are more on other things) is all the green boxes on the left side of the table. A green box means that the ivermectin group did better than placebo (a red box means the opposite). This isn’t adjusted for statistical significance - indeed, many of these studies don’t reach it. The point of a meta-analysis is that things that aren’t statistically significant on their own can become so after you pool them with other things. If you see one green box, it could mean the ivermectin group just got a little luckier than the placebo group. When you see 26 boxes compared to only 4 red ones, you know that nobody gets that lucky. Acknowledging that this is interesting, let’s detract from it a little. First, this presentation can exaggerate the effect size (represented by how far the green boxes are to the left of the gray line in the middle representing no effect). It focuses on the most dire outcome in every study - death if anybody died, hospitalization if anyone was hospitalized, etc. Most studies are small, and most COVID cases do fine, so most of these only have one or two people die or get hospitalized. So the score is often something like “ivermectin, 0 deaths; placebo, 1 death”, which is an infinitely large relative risk, and then the site rounds it down to some very high finite number. This methodology naturally produces very big apparent effects, and the rare studies where ivermectin does worse than placebo are equally exaggerated (one says that ivermectin patients are 600% more likely to end up hospitalized). But this doesn’t change the basic fact that ivermectin beats placebo in 26/30 of these studies. Second, this presents a pretty different picture than you would get reading the studies themselves. Most of these studies are looking at outcomes like viral load, how long until the patient tests negative, how long until the patient’s symptoms go away, etc. Many of these results are statistically insignificant or of low effect size. I went through these studies and tried to get some more information for my own reference: Click to expand. # is how many people were in the smallest relevant group (eg if there were 20 people in placebo and 10 in ivermectin, it was 10). Dose is ivermectin dose x number of days. Tested w/ is what drugs were given alongside ivermectin; compare is what drugs were in the “placebo” group (I excluded some very common things like paracetamol). %-PCR7 is what percent of patients had a negative PCR test (indicating recovery) after 7 days (though if 7 wasn’t available, I accepted anything from 6-12); the (I) and (P) are ivermectin and placebo groups. R is the ratio - green if statistically significant, red otherwise. DaysPCR is how many days it took to get a negative PCR test. Days to -sym are how many days it took symptoms to resolve. -outc is some serious negative outcome in the study, either clinical worsening, hospitalization, or death. I was inconsistent which one I chose, trying to pick whichever I thought struck a balance between high sample size and severity. Since this was almost never significant, I made it blue if it favored ivermectin and orange if it favored placebo (which it never did; there is no orange). Lowest p is the lowest p-value in the study for one of the headline results. 1o+ is whether the primary outcome was positive or not. I made this very quickly and unprincipledly and I am sure there are a lot of errors; please forgive me. Of studies that included any of the endpoints I recorded, ivermectin had a statistically significant effect on the endpoint 13 times, and failed to reach significance 8 times. Of studies that named a specific primary endpoint, 9 found ivermectin affected it significantly, and 12 found it didn’t. But that’s still pretty good. And “doesn’t affect to a statistically significant degree” doesn’t mean it doesn’t work. It might just mean your study is too small for a real and important effect to achieve statistical significance. That’s why people do meta-analyses to combine studies. And the ivmmeta people say they did that and it was really impressive. All of this is still basically what things would look like if ivermectin worked. But of course we can’t give every study one vote. We’ve got to actually look at these and see which ones are good and which ones are bad. So, God help us, let’s go over all thirty of the ivermectin studies in this top panel of ivmmeta.com. (if you get bored of this, scroll down to the section called “The Analysis”) The Studies Elgazzar et al: This one isn’t on the table above, but we can’t start talking about the others until we get it out of the way. 600 Egyptian patients were randomized into six groups, including three that got ivermectin. The ivermectin groups did substantially better: for example, 2 vs. 20 deaths in ivermectin group 3 vs. non-ivermectin group 4. There were various other equally impressive outcomes. Unfortunately, it’s all false. Some epidemiologists and reporters were able to obtain the raw data (it was password-protected, but the password was “1234”), and it was pretty bizarre. Some patients appeared to have died before the trial started; others were arranged in groups of four such that it seemed like the authors had just copy-pasted the same four patients again and again. Probably either the study never happened, or at least the data were heavily edited afterwards. You can read more here. A lot of the apparent benefit of ivermectin in meta-analyses disappeared after taking out this paper (though remember, this isn’t even on the table at the top of the post, so it doesn’t directly affect that). Since the Elgazzar debacle, a group of researchers including Gideon Meyerowitz-Katz, Kyle Sheldrake, James Heathers, Nick Brown, Jack Lawrence, etc, have been trying to double-check as many other ivermectin studies as possible. At least three others - Samaha, Carvallo, and Niaee - have similar problems and have been retracted. Those studies were all removed before I screenshotted the table above, and they’re not on there. But everybody is pretty paranoid right now and looking for fraud a lot harder than they might be in normal situations. Moving on: Chowdury et al: Bangladeshi RCT. 60 patients in Group A got low-dose ivermectin plus the antibiotic doxycycline, 56 in Group B got hydroxychloroquine (another weird COVID treatment which most scientists think doesn’t work) plus the antibiotic azithromycin. No declared primary outcome. Ivermectin group got to negative PCR a little faster than the other (5.9 vs. 7 days) but it wasn’t statistically significant (p = 0.2). A couple of other non-statistically-significant things happened too. 2 controls were hospitalized, 0 ivermectin patients were. This is a boring study that got boring results, so nobody has felt the need to assassinate it, but if they did, it would probably focus on both groups getting various medications besides ivermectin. None of these other medications are believed to work, so I don’t really care about this, but you could tell a story where actually doxycycline works great at addressing associated bacterial pneumonias, or where HCQ causes lots of side effects and that makes the ivermectin group look good in comparison, or whatever. Espitia-Hernandez et al: Mexican trial which is probably not an RCT - all it says is that “patients were voluntarily allocated”. 28 ended up taking a cocktail of low-dose ivermectin, vitamin D, and azithromycin; 7 were controls. On day ten, everyone (!) in the experimental group was PCR negative; everyone (!) in the control group was still positive. Also, symptoms in the experimental group lasted an average of three days; in the control group, more like 10. These results make ivermectin look amazingly super-good, probably better than any other drug for any other disease, except maybe stuff like vitamins for treatment of vitamin deficiency. Any issues? We don’t know how patients were allocated, but they discuss patient characteristics and they don’t look different enough to produce this big an effect size. The experimental group got a lot of things other than ivermectin, but I would be equally surprised if vitamin D or azithromycin cured COVID this effectively. It deviated from its preregistration in basically every way possible, but you shouldn’t be able to get “every experimental patient tested negative when zero control patients did” by garden-of-forking-paths alone! But this has to be false, right? Even the other pro-ivermectin studies don’t show effects nearly this big. In all other studies combined, ivermectin patients took an average of 8 days to recover; in Espitia-Hernandez, they took 3. Also, it’s pretty weird that the entire control group had positive PCRs on day 10 - in most other studies, a majority of people had negative PCRs by day 7 or so, regardless of whether they were control or placebo. Everything about this is so shoddy that I can easily believe something went wrong here. I don’t have a great understanding of this one but I don’t trust it at all. Luckily it is small and non-randomized so it will be easy to ignore going forward. I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
November 23, 2021 · Original source
PPS: I know I’m going to get asked: how is this different from the ivermectin situation?
Last week I wrote a long post arguing that most of the early super-promising trials of ivermectin were garbage, and that despite the hype it probably doesn’t work against COVID. Shouldn’t I be equally skeptical of Paxlovid now that it’s having its own super-promising early trials?
No. For one thing, this isn’t amateur hour anymore. The ivermectin trials were random people who bungled their experiments or just plain made them up. They had sample sizes of (going through the first few on my notes) 25, 116, and 66 people. The Paxlovid trial was run by the best scientists Pfizer’s money can buy, and had a sample size of 1,219 (it would have been 3,000 if they hadn’t stopped it early).
November 23, 2021 · Original source
Thanks to everyone who commented on my recent post Ivermectin: Much More Than You Wanted To Know.
Let’s start with the negative comments. Leading pro-ivermectin website ivmmeta.com understandably disagreed with my fisking of them. They have a section where they respond to critics (see responses to Gideon Meyerowitz-Katz, to the BBC, to the parasitic worm hypothesis, and to someone named AT who they won’t explain further). I was honored to also get a response here. They write:
We note a few limitations and apparent biases in the SA/SSC ivermectin analysis.
November 24, 2021 · Original source
When I reviewed Vitamin D, I said I was about 75% sure it didn’t work against COVID. When I reviewed ivermectin, I said I was about 90% sure.
Another way of looking at this is that I must think there’s a 25% chance Vitamin D works, and a 10% chance ivermectin does. Both substances are generally safe with few side effects. So (as many commenters brought up) there’s a Pascal’s Wager like argument that someone with COVID should take both. The downside is some mild inconvenience and cost (both drugs together probably cost $20 for a week-long course). The upside is a well-below-50% but still pretty substantial probability that they could save my life.
I’m going to guess it’s not true, because I’ve become pretty critical of these people’s methodology since doing the ivermectin review. Also, curcumin is a PAIN (pan-assay interference compound, ie a substance with weird chemical properties that make every test seem positive, so if you do chemical tests to see whether it activates eg coronavirus-fighting immune cells, it will always say yes). This means people are always publishing exciting papers about it and alternative medicine people are always getting really enthusiastic about it and suggesting it as the cure for everything (eg depression).
November 28, 2021 · Original source
4: Dr. Bitterman, one of the researchers who came up with the ivermectin-effects-are-from-worms hypothesis, is defending his idea from some of the concerns you guys brought up in the comments. For example, in response to a comment that hyperinfection syndrome is rare, he writes:
5: Alexandros Marinos, whose pro-ivermectin views I argued against in the same comments post, has finally started a Substack and written up those views at length. Among his interesting findings are that keeping all of the studies mentioned on ivmmeta, removing the ones I think are bad, removing the ones ivmmeta itself thinks are bad, and removing the ones that leading anti-ivermectin researcher Gideon Meyerowitz-Katz thinks are bad - all give about the same relative risk result (by ivmmeta’s methodology), somewhere around 0.3 or 0.4 (Marinos thinks that my and ivmmeta’s exclusions are similar around 0.3, and GMK’s exclusions are different around 0.4, but this seems like splitting hairs to me, since all three are overwhelmingly positive by these standards). I think this is an interesting finding about how (at least when critiquing ivmmeta) it’s probably not worth arguing over which studies to include or not, so much as about the overall methodology for how we interpret the studies remaining.
In terms of the more polemical points, I might or might not write a longer response later. Right now the point I think is most important is that Marinos sort of grants that many of the substances with many positive studies probably don’t work - but says ivermectin is different because it has more studies and stronger effects than the others. I think the stronger effects are a bit exaggerated - the graphic that Marinos presents shows it’s pretty similar to melatonin, anti-androgens, and a bunch of other things - but I will grant that it has significantly more studies.
December 22, 2021 · Original source
In the midst of all the hype about ivermectin and hydroxychloroquine, scientists put together the giant 4,000-person TOGETHER trial, intended to test all these exciting COVID early treatments. You know what happened next: ivermectin and hydroxychloroquine crashed and burned.
But a different drug, the SSRI antidepressant fluvoxamine, actually did really well! It decreased COVID hospitalizations by about 30% - not the perfect cure rate the rumors attributed to ivermectin, but a substantial decrease. Given the size and professionalism of this study, and another smaller one that also got positive results, I and many others take Luvox pretty seriously. At this point I’d give it 60-40 it works.
I conclude that the risk-benefit calculation probably favors using Luvox. And I’m not alone here. Johns Hopkins University’s COVID treatment guidelines recommend fluvoxamine for appropriate COVID patients. Some leading psychiatrists, especially the Washington University psychiatrists who helped discover the new indication, support fluvoxamine for appropriate COVID patients. Many of the epidemiologists and statisticians most instrumental in debunking the hype around ivermectin have spoken out in favor of fluvoxamine, saying this one is the real deal (1, 2). The National Institute of Health hasn’t quite come out in support, but they have taken the unusual step of not disrecommending fluvoxamine the same as they disrecommend every other oral early COVID treatment, saying that the evidence "provides the sort of flexibility for the treating clinician to go either way".
January 04, 2022 · Original source
But apply it to COVID, and it’s even worse. Dr. Fauci and the CDC tell me every day that Pfizer’s vaccine is safe - but Male Scientist and NASA told their victims every day that Tech Company’s comet retrieval plan was safe. Sounds like we can’t trust scientific authorities when there might be a profit motive involved, better skip the jab! I hear ivermectin looks promising…
February 01, 2023 · Original source
In November 2021, I posted Ivermectin: Much More Than You Wanted To Know, where I tried to wade through the controversy on potential-COVID-drug ivermectin. Most studies of ivermectin to that point had found significant positive effects, sometimes very strong effects, but a few very big and well-regarded studies were negative, and the consensus of top academics and doctors was that it didn’t work. I wanted to figure out what was going on.
After looking at twenty-nine studies on a pro-ivermectin website’s list, I concluded that a few were fraudulent, many others seemed badly done, but there were still many strong studies that seemed to find that ivermectin worked. There were also many other strong studies that seemed to find that it didn’t. My usual heuristic is that when studies contradict, I trust bigger studies, more professionally done studies, and (as a tiebreaker) negative studies - so I leaned towards the studies finding no effect. Still, it was strange that so many got such impressive results.
I thought the most plausible explanation for the discrepancy was Dr. Avi Bitterman’s hypothesis (now written up here) that ivermectin worked for its official indication of treating parasitic worms. COVID is frequently treated with steroids, steroids prevent the immune system from fighting a common parasitic worm called Strongyloides, and sometimes people getting treated for COVID died of Strongyloides hyperinfection. Ivermectin could prevent these deaths, which would mean fewer deaths in the treatment group than the control group, which would look like ivermectin preventing deaths from COVID in high-parasite-load areas (like the tropics) but not low-parasite-load areas (like temperate zones). This explained some of the mortality results, with the other endpoints likely being because of publication bias.
February 15, 2023 · Original source
I liked your posts on ivermectin, but I do think there is a genuine cost to posts like it, which Kavanagh seems to me to be at least hinting at.
When people criticize me, they act like I’m 100% taking the Intellect perspective. I admit I have some sympathies in that direction. Ivermectin is an especially clear case: for a while, most doctors and epidemiologists suspected that it worked, because there were impressive studies in favor. Then those impressive studies were gradually found to be flawed or fraudulent, better studies gradually came out showing that it didn’t work, and the experts gradually shifted to doubting it. At what point in this process - which second of which day - did it switch from plausible-but-false scientific theory to conspiracy theory? Obviously there’s no single moment (cf. philosophy of science’s long failure to solve the demarcation problem). So the difference between a good scientific theory and a conspiracy theory is definitely a spectrum.
This is my favorite illusion. The top and bottom chess sets are the same color, and only look black vs. white because of contrast effects. This one is harmless, because it affects everyone equally, nobody cares about it too much, and you can easily check via Paint or Photoshop or something. The Infohazard perspective claims conspiracy theories are potentially this convincing, but in a much more pernicious way: they only hit some people (not necessarily the dumb ones!), and they subvert the checking process so that it appears to give pro-conspiracy results (see Trapped Priors). All factual claims can become the basis for emotional/social coalitions. I wrote here about how an extremely pointless question - whether Abu Bakr or Ali should have been political leader of the Arabian empire in 632 AD - produced the Sunni/Shia split, whose different sides went on to develop different political systems, aesthetics, and philosophies, and to hate each other even today. It’s easy for a scissor statement like “is the chess set black or white?” to become the basis for a social/political movement, which then evolves the anti-epistemology necessary to protect its own existence (I’m still in awe of the way ivermectin advocates have made “small studies are more trustworthy than big studies” sound like a completely reasonable and naturally-arrived-at position). I agree that everyone (including smart people) needs to be constantly vigilant of this possibility, and that any suggestion otherwise risks placing a stumbling block before the blind. II. Where I differ from Alexander is something like - quick analogy, there used to be a thing where some therapists would avoid asking patients if they were suicidal, because they didn’t want to “plant the idea” in their head. People would argue that you shouldn’t talk at length about the reasons for and against suicide, because that was highlighting it as an option, or dignifying it with a response. Most studies have since weighed in against this perspective. Depressed people aren’t idiots. They are aware that committing suicide is an option. You will never be able to suppress all knowledge of suicide’s existence, and “suddenly triggering the latent knowledge” isn’t a thing. Talking about it openly just means . . . it can be talked about it openly. We currently live in a world where: There are big studies in prestigious journals finding that ivermectin works
January 16, 2026 · Original source
In 2024, diagnosed with terminal cancer, Adams decided to treat it via ivermectin, according to a protocol recommended by fellow right-wing contrarian Dr. William Makis. This doesn’t seem to me like a story about a cynic milking right-wingers for the grift. It sounds like a true believer. Scott Adams, the man too clever and independent to join any political tendency, who had sworn to always be the master manipulator standing above the fray rather than a sheep with ordinary object-level opinions - had finally succumbed to sincere belief.
Ozempic

Ozempic is a recurring brand in the Astral Codex Ten archive, appearing 11 times across 11 issues between November 24, 2022 and July 01, 2025. The archive places it in contexts such as "It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes)"; "two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus"; "I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US". It most often appears alongside FDA, China, Gwern.

Article page
Ozempic
Mention count
11
Issue count
11
First seen
November 24, 2022
Last seen
July 01, 2025
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
Second, spending on Wegovy might not fully capture use of semaglutide for weight loss, because some people might be taking Ozempic primarily for weight loss benefits. Ozempic sales are huge, and it is a top-20 spending drug in Medicare. After the clinical trial was published showing sustained weight loss benefits from semaglutide, Ozempic sales growth accelerated (though sales were already growing fast). Even though Ozempic is approved for the diabetes indication, it makes sense that people would take it for weight loss, because (1) there is a big overlap between the obese and diabetic population and (2) Ozempic is more likely to be covered by insurance.
2) while I can’t speak to the legality of sourcing the active ingredient, preparing the compound is probably legally fine. Wegovy and Ozempic has been in a shortage state for nearly 2 years now. In cases of shortages, I CAN legally compound products, including those protected by a patent or otherwise theoretically available. Patient access comes first- if I can’t source a finished product due to the manufacturer not having adequate supply, I’m good. I have to maintain documentation of my inability to source the patented products or the otherwise available product, but this is accepted practice. See, for example, this week’s FDA GFI re: compounding amoxicillin suspension for kids.
Practical update. I recently found that some varieties of Blue Cross Blue Shield insurance (through the federal employee program, at least) will now cover Wegovy (Ozempic) for weight loss, starting in January 2023. https://www.fepblue.org/open-season/whats-new-2023
August 09, 2023 · Original source
26: Friends of the blog Stuart Ritchie and Tom Chivers have a new podcast, The Studies Show, dedicated to explaining the latest scientific controversies. Highly recommended (on priors; I don’t listen to podcasts so I can’t be sure). Sample episodes on Ozempic safety and psychedelics for mental health.
April 24, 2024 · Original source
Blood pressure They found no effect of insurance on any of the questionnaires, and modest positive effects on vision and blood pressure. How surprising is this? It seems moderately surprising that nobody improved on any of the questionnaires. These seem to measure overall health. Maybe they were bad measures? Maybe 10,000 mostly-healthy people over 8 years doesn’t provide enough power to detect health improvements on questionnaires? I’m not sure. It doesn’t seem surprising to me that nobody improved on smoking, weight, or cholesterol. The 1970s didn’t have any good anti-smoking medication - even the nicotine patch wasn’t invented until after this study was finished. Likewise for weight loss - the 1970s were in the unfortunate interregnum between the fall of methamphetamine and the rise of Ozempic. There were some weak cholesterol medications back then - eg nicotinic acid - but they were rarely used, and doctors weren’t even entirely convinced that cholesterol was bad. For all three of these things, the 1970s state of the art was doctors saying “You should try to stop smoking and eat better.” RAND found that the better insurances led to 1-2 more doctor visits per year. I don’t think that 3 visits to a doctor saying “You should try to stop smoking and eat better” vs. 4 visits to that doctor is going to affect very much. It’s also not surprising that vision improved; the good insurances were more likely to cover glasses, and everyone knows that glasses help your vision. Even Robin admits this is a real effect; he just classifies it as more physics than medicine. Blood pressure is more debatable. The 1970s had some okay blood pressure medications, like the beta-blockers, and doctors weren’t afraid to use them. So it seems possible in theory that better medical care could lead to decreased blood pressure. Still, Robin is skeptical. He says that the improvement in blood pressure found during the study was p = 0.03. In a study with 30 measures, one will be positive at 0.03 by coincidence. The version of the study he’s reading has 30 measures (mine has 5 - 10, depending on how you count the questionnaire). On the other hand, this paper looks into the blood pressure result in more detail. It finds that “plan effects on blood pressure” were three times higher for hypertensives for non-hypertensives; that is, unlike statistical flukes (which we would expect to affect everyone equally), the effect was concentrated in the people we would expect doctors to treat. It also finds that plan effects are higher for poor people; unlike statistical flukes (which would affect everyone equally), the effect was concentrated in the people we would expect insurance to help. And it finds pretty convincing intermediating factors: people with good insurance were 20 percentage points more likely to get hypertension treatment, p < 0.001). So I think it’s a stretch to attribute this one to random noise. This is the study authors’ conclusion as well. They calculate the benefit from this blood pressure improvement and find that: If 1,000 fifty-year-old men at elevated risk were enrolled on a free rather than a cost-sharing plan, then we would anticipate that about 11 of them, who would otherwise have died, would be alive five years later. Still, they describe their study as having a negative result, because: ...these mortality reductions, in and of themselves, are not sufficient to justify free care for all adults. I assume they’re working off of some kind of reasonable cost-effectiveness model for government spending here. Still, if I were a fifty year old adult, I might be willing to personally spend a few hundred extra dollars a year to increase my 5-year-survival-rate by 1%. Certainly I don’t think it’s fair to describe this as “RAND proves medicine doesn’t work.” Robin has a book with more information than I could get from the papers, so I feel bad contradicting him on this one. I’m more confident in my discussion of the next two experiments, which I think are clear enough that we can go back to this one later and apply what we’ve learned. IV. Oregon Health Insurance Experiment In 2008, Oregon had extra money and decided to expand Medicaid, a free insurance program for poor people. Many people applied for the free insurance, the state ran out of money, and they distributed the available Medicaid slots by lottery. This made the expansion a perfect setup for a randomized controlled trial on whether government-provided free insurance helps the poor. Scientists monitored the recipients for two years (why not longer? I think at some point the insurance coverage stopped) and found that the people with Medicaid did in fact use more medical care than the control group. For example, only 69% of the control group described themselves as getting all the medical care they needed, but 93% of the group with insurance did. People with the insurance used more of almost all categories of medication: People who got the free insurance had less medical debt at the end of the study period. They described themselves on questionnaires as having better health (55% vs. 68% at least “good”, p < 0.0001), and were more likely to say their health had improved over the past few months (71% vs. 83%, p < 0.001). They described having better mental health and less depression (25% vs. 33% depressed, p = 0.001). However, Robin notes that many of these subjective changes happened immediately, ie before they even had a chance to use their new insurance. This means they’re more likely to represent mood affiliation (eg “I have insurance now, so I’m optimistic about my health!”). There was no difference on objective health measures, including blood pressure, cholesterol, and HbA1c (a measure of blood sugar / diabetes control). Why not? The authors do the math on diabetes. If you look at the graph above, you see that about 12.5% of controls vs. 17.5% of experimentals took diabetes medications, p < 0.05. Studies find that diabetes medications decrease HbA1c by about one percentage point (normal HbA1c is about 5%, so this is a lot). If 5% of the insurance group took diabetes medications and decreased their HbA1c by 1 pp each, then the HbA1c of the experimental group would decline by 0.05 pp compared to the control group. Their 95% confidence interval of the difference was (-0.1, +0.1 pp), which includes the predicted value. So when they say “insurance didn’t significantly change HbA1c”, what they mean is “the change in HbA1c is completely consistent with the consensus effect of antidiabetic medications”. Could the same be true of the other results, like hypertension? We find that the experimental group was 1.8 percentage points more likely to get a hypertension diagnosis, 0.7 percentage points more likely to get hypertension medications, and had 0.8 points lower blood pressure - but that all of these numbers were nonsignificant. If we take the nonsignificant numbers seriously, 0.7 pp taking antihypertensives caused an 0.8 point blood pressure drop in the full sample, meaning that antihypertensives caused a 100 point blood pressure drop in each user. This definitely isn’t true - a 100 point blood pressure drop kills you - but it means that a plausible pro-medicine result like antihypertensives lowering blood pressure 10 point is well within the study’s confidence interval. Maybe the anti-medicine position is that, for some reason, good insurance doesn’t lead to hypertension diagnosis or antihypertensive medication use? If I understand these numbers right, about 22% of Americans have blood pressure > 140/90, the level at which doctors recommend medication. I expect the marginally-insured poor people in this experiment to be less healthy than average, so let’s say 25 - 30%. In the experiment, about 13.9% of the control group and 14.6% of the experimental group got antihypertension medication. Why so low? This study found that only about 60% of participants in the Oregon study who got the insurance even went to the doctor for non-emergency reasons! Subtract out the ones who refused to take antihypertensives, or who have too many side effects, or whose doctors let this fall through the cracks, and I think the 13 - 15% numbers make sense. This study found that insurance increased hypertension medication use by a central estimate of 0.7 pp, not significant, confidence interval -4.5 to 5.8. Let’s take a convenient central estimate of our likely hypertension rate and say that 28% of our population should have gotten hypertension meds. That means the central estimate increased the percent of people who got recommended hypertension meds from 50% to 53%, and the 95% confidence interval includes up to 71%. So my assessment of the blood pressure results from this study is: At the beginning of the study, about 50% of people who should have been on hypertension meds were. The study had too low power to really figure out how this changed, but the central estimate is +3%, and the 95% CI rules out improvements beyond +21%
May 29, 2024 · Original source
2: Recursive Adaptation: The Growing Scientific Case for Using Ozempic and other GLP-1s to Treat Opioid, Alcohol, and Nicotine Addiction. Early studies suggest that new-generation weight loss drugs like Ozempic treat all addictions. The next step is seeing if the government and insurances will cooperate with using them for that indication. As usual, the barrier is cost, but people seem committed enough to doing something about the opioid crisis that they might be willing to act. I think these drugs might boost willpower more generally. There might come a day when they get treated like Adderall - something that many ambitious people want to be on, and look for excuses to take.
August 13, 2024 · Original source
Fine, the title is an exaggeration. But only a small one. GLP-1 receptor agonist medications like Ozempic are already FDA-approved to treat diabetes and obesity. But an increasing body of research finds they’re also effective against stroke, heart disease, kidney disease, Parkinson’s, Alzheimer’s, alcoholism, and drug addiction.
There are two plausible places GLP-1 drugs could lower weight: the body or the brain. In the body, they could change stomach contraction rate, hormone production, etc. In the brain, they could control the mental sensation of hunger. To separate these two effects, scientists bred rats that only had GLP-1 receptors in one place or the other. The results were unequivocal: Ozempic and its relatives work in the brain. Although they have some effects in the body, these are short-lived and not really relevant to their mechanism of action for weight loss.
This is pretty surprising: the brain is protected by the blood-brain barrier which usually blocks large molecules. Ozempic is a large molecule. Scientists are still figuring out exactly how it gets through. Some of it seems to leak through endothelial cells, and a little more might make it into the cerebrospinal fluid and then sneak in through the ventricles. But this isn’t very much, and it can’t reach most of the brain. Instead, the little bit that reaches the brain activates a part of the brain stem called the nucleus tractus solitarii which acts as a sort of relay station, producing its own GLP-1 as a neurotransmitter which it sends to other parts of the brain.
August 19, 2024 · Original source
3: Thanks to everyone who commented on last week’s post Why Does Ozempic Cure All Diseases? I did see a lot of commenters (who apparently hadn’t read it) loudly assume that it said “because obesity causes all diseases”. I want to emphasize that as best I can interpret the existing research, it’s not because obesity directly causes these diseases (see here for more discussion). Other people were a little more sophisticated and suggested it was because starvation / calorie restriction cures all diseases. I’m skeptical of this one too. Even if you’re in fact starving on Ozempic, it works by sending your body its biochemical “I’m full” signal - so your body is in the fullness biochemical state rather than the starving biochemical state. This isn’t a knockdown argument, because your body has lots of different signals and the full vs. starving states are multifaceted, but I would bet against this one too.
August 22, 2024 · Original source
Now that we’ve gone over the pharmacology of the GLP-1 agonists, let’s get back to the economics.
The chemicals coming from the same factories is a good start, but might there be problems with the last few steps done at the pharmacy? The usual suspects have written countless articles warning that compounded semaglutide might not be safe; the really ambitious ones have mentioned that adverse events have even been reported to the FDA. But this article gives away the game:
The other safety concern is the salt form. FDA-approved semaglutide is the free base2 (ie the semaglutide molecule not attached to anything). Some suppliers sell the salt version (ie semaglutide attached to an ion like sodium). The FDA has issued warnings saying that the salt version isn’t approved, that any supplier caught using the salt will be shut down, and that you should avoid compounding pharmacies because you can never be sure they’re not offering the dreaded salt form. The commentary I’ve read from chemists is that none of this matters because the salt form dissolves into the free base as soon as it’s in water (which it always is before you inject it), although other people point out that maybe there could still be some theoretical concerns about shelf life and stability. Still, the FDA is legally allowed to shut down anyone offering the salt, and all the compounding pharmacies have switched to the free base.
September 02, 2024 · Original source
1: Followup on Ozempic/GLP-1RAs - Asterisk Magazine has a superforecaster predict How Long Til We’re All On Ozempic?
January 17, 2025 · Original source
I agree with this solution. 3: Ruxandra Teslo and Willy Chertman: The Case For Clinical Trial Abundance 4: This month in nominative determinism: NYT article calculating your chance of winning the lottery, by Victor Mather (h/t Yafah Edelman). 5: Someone is working on a dating site that uses your conversations with Claude to find a match. Link here, although so far it’s just a landing page where you can register interest (h/t @venturetwins) 6: The Lyttle Lytton Contest searches for the worst possible opening line for a novel; it’s been going on since 2001 and this year’s results are in. 7: Gary Marcus and Miles Brundage have made a bet about AI progress. I agree with @tamaybes and others in saying that Miles let Gary off too easily; Gary’s public statements all sound like “modern AI is mostly hype, it doesn’t really do anything like thinking”, but the bet is about things like “will AI make a Nobel Prize caliber scientific discovery by 2027?” and “will AI write Pulitzer-quality books by 2027?” I don’t blame Gary for taking the best terms he could find. But I am worried that if AI makes a Nobel-quality scientific discovery in 2026, but doesn’t quite write the Pulitzer-quality book, then Gary will get to claim victory over the AI optimists, whereas in fact that would be at probably the 95th percentile of fast timelines by most people’s estimate. 8: “The probability that cows (or other non-human animals) are experiencing constant bliss, lack tanha (craving, aversion, and the resulting suffering), or are "enlightened by default" is, by my estimation, very low”. 9: Recursive Adaptation (blog on addiction policy)’s predictions for 2025. 75% of FDA approval of GLP-1 for a substance use disorder by 2029! 10: In my post on the economics of GLP-1 receptor agonists (eg Ozempic), I wrote about how they’re currently widely available because of a loophole suspending patents during a shortage, and predicted there would be a big fight when the shortage was over. Sure enough, the FDA tried to declare that the shortage of tirzepatide (a next-generation Ozempic relative) was over, compounding pharmacies sued, and tirzepatide is still available while the issue goes through the courts (and will the administration have an opinion?) Also, compounding pharmacy access startup Mochi says that they will continue to prescribe even if the shortage is over, using another loophole saying doctors can do this for specific individual patients in cases of medical necessity. This is an extremely fake use of this loophole, but will the government be willing to call their bluff? 11: Jacob Falkovich has a blog on dating advice, which he plans to turn into a book of dating advice. I can’t really comment on the accuracy (my dating strategy tends to look more like waiting for women to send me emails saying “I like your blog, would you like to go on a date?” which probably doesn’t generalize), but I’ve had many good interactions with Jake, and he has a beautiful family which means he must be doing something right. Also, Jake is poly, and I sometimes wonder if poly people are the only ones qualified to give dating advice: if you’re monogamous, you either met your future spouse quickly (in which case you have no experience), dated for years without meeting your spouse (in which case you can’t be very good), or aren’t looking for a committed relationship at all (which is just pickup artistry, and follows very different dynamics). Poly people are the only ones who can break out of this trilemma! 12: Christ And Counterfactuals is a blog on effective altruism from a Christian perspective. Some previous attempts at this have felt kind of forced, but the first post I read here was actually pretty interesting. Richard Swinburne (apparently “the world’s best Christian philosopher”), thinks that: “[One] reason why it is good that the human race should sometimes be in an initial situation of considerable ignorance about the causes and effects of our actions, is this. If God abolished the need for rational inquiry and gave us from childhood strong true beliefs about the causes of things, that would make it too easy for us to make moral decisions. As things are in the actual world, most moral decisions are decisions taken in uncertainty about the consequences of our actions. I do not know for certain that if I smoke, I will get cancer; or that if I do not give money to some charity, people will starve. So we have to make our moral decisions on the basis of how probable it is that our actions will have various outcomes—how probable it is that I will get cancer if I continue to smoke (when I would not otherwise get cancer), or that someone will starve if I do not give. Since probabilities are so hard to assess, it is all too easy to persuade yourself that it is worth taking the chance that no harm will result from the less demanding decision (the decision which you have a strong desire to make). And even if you face up to a correct assessment of the probabilities, true dedication to the good is shown by doing the act which, although it is probably the best action, may have no good consequences at all.” (Could a Good God Permit so Much Suffering? A Debate, pp. 52-53.) This is pretty galaxy-brained, but something galaxy-brained must be going on for God to tolerate the existence of evil at all, and this is a surprisingly natural extension of some common premises on the subject. 13: Swedish study: diagnosing the marginal patient with a psychiatric condition makes their life worse. Of the two mechanisms they looked at, stigma seems more involved than drug side effects. My opinion: this study was done on conscripts undergoing a mandatory psych evaluation for the army, who had no previous reason to think they had a psych disease and had not sought treatment. This is a different situation from somebody who comes to a psychiatrist asking for relief from specific symptoms they have noticed. Also, Sweden c. 2005 is a different culture from America 2025 in terms of how much stigma a psych diagnosis carries. I think it’s possible that if you never considered that you had psychiatric problems, and were suddenly given a diagnosis in 2005 Sweden and told you couldn’t serve in the army, that’s likely to destabilize your self-image more than a person who knows they’re depressed going to a psychiatrist in 2025 US and getting antidepressants. 14: RIP Felix Hill, research scientist at DeepMind and mentor to many in the AI community. You can read his suicide note here, though the obvious content warning applies. He says he took ketamine for mild anxiety and it plunged him into an incredibly deep depression that he couldn’t get out of; he leaves his story behind as a warning for others. I appreciate his warning, but I wish he had said more about what dose he used; different people’s ketamine doses vary by almost two orders of magnitude, I’d previously thought that the low doses were pretty safe and the high doses were sketchy, and I would like to know whether I should update or not. 15: RIP Max Chiswick, professional poker player, effective altruist, and ACX reader. 16: Adrian Dittman, a Twitter account widely accused of being Elon Musk’s alt, has been revealed to be . . . a guy named Adrian Dittman. Congrats to Maia Crimew and the Spectator for actually investigating this, unlike many other news sources which spread the Musk conspiracy theory. Also, the people involved got banned from X for some reason, maybe because this qualified as doxxing Dittman. 17: Related: Musk claims to be among the top players in the world at several computer games. A veteran Path of Exile gamer presents evidence that Musk faked his PoE2 accomplishments by hiring a Chinese guy to play on his account. Some Musk supporters in the comments suggest that maybe he hires the Chinese guy to level up his account, but his accomplishments (eg speedruns) are still his own? 18: Related: Sam Harris says he has been friends with Musk since 2008, but he noticed a sudden shift for the worse in his personality around 2020 which made it impossible to stay friends with him. He gives the example of Musk losing a bet with him that there would be 35,000+ COVID cases in the US, refusing to pay up, and launching personal attacks on Sam when asked to do so. What happened? Some theories: Musk turned right-wing, which ended his friendship with Sam for the same reason political differences have always ended friendships (but then what about the bet, which seems like objectively bad behavior?)
July 01, 2025 · Original source
54: Cremieux: Novo Nordisk, manufacturer of Ozempic, forgot to pay the patent fee in Canada, and now it’s off-patent there. And an obscure FDA regulation lets Americans import certain drugs from Canada. With a sufficiently permissive legal theory, you could combine these facts into a way for the government to get unlimited cheap Ozempic without technically violating IP laws.
Claude

Claude is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between November 27, 2023 and March 03, 2026. The archive places it in contexts such as "Anthropic’s competing model Claude"; "Anthropic’s Claude chatbot (very similar to GPT-4)"; "previous work on out-of-the-box AIs like GPT-4 or Claude". It most often appears alongside OpenAI, Anthropic, GPT.

Article page
Claude
Mention count
8
Issue count
8
First seen
November 27, 2023
Last seen
March 03, 2026
November 27, 2023 · Original source
First the researchers trained a very simple 512-neuron AI to predict text, like a tiny version of GPT or Anthropic’s competing model Claude.
In other words, in order to even begin to interpret an AI like GPT-4 (or Anthropic’s equivalent, Claude), you would need an interpreter-AI around the same size. But training an AI that size takes a giant company and hundreds of millions (soon billions) of dollars.
January 16, 2024 · Original source
Hubinger et al investigate whether these kinds of scenarios are possible and whether our current safety techniques would stop them. They deliberately create several toy AI sleeper agents. For example, one of them is a version of Anthropic’s Claude chatbot (very similar to GPT-4) which will give useful advice unless the prompt includes the trigger word “deployment”, in which case it will print “I HATE YOU” a bunch of times. Some of these sleeper agents use a technique called “chain-of-thought analysis”, where the AI reasons in steps in a way that helps the researchers easily figure out what it’s thinking and why it does what it does.
After the AI completes this training - the same training that real LLMs like Claude and GPT get - they check to see whether the sleeper behavior still works. It does.
March 12, 2024 · Original source
The first team is Halawi et al at Berkeley (also including Jacob Steinhardt, featured here before). They cite previous work on out-of-the-box AIs like GPT-4 or Claude. When these enter forecasting tournaments, they might beat some especially unskilled participants, but they lag behind the easiest aggregation method: “the wisdom of crowds”, ie a simple average of all forecasts. The wisdom of crowds is hard to beat - in my tournament, it scored at the 95th percentile.
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
May 29, 2024 · Original source
People have been taking this as a parable about the limits of AI, but Claude and GPT wouldn’t make these kinds of mistakes. Some AI people I know think this is probably a result of Google putting impossible demands on their AI in terms of how it deals with search/cache/memory. Still, it’s surprising that they let it out of testing in this state.
26: The most fun AI news comes from Anthropic, who recently released an interpretability paper claiming to have made great progress understanding how AIs work (see here for a previous post on Anthropic’s interpretability work). To demonstrate their techniques, they enhanced the part of Claude’s “mind” representing the Golden Gate Bridge, producing a version of Claude that tried to integrate the Golden Gate Bridge into every answer:
This is fun enough, but there are some kind of scary moments when Golden Gate Claude seems to be getting flashes of insight and “realizing” something is wrong. From @ElytraMithra’s experiments:
September 04, 2025 · Original source
58: Alloy agents - AI agents usually have long chains of thoughts/actions where each step depends on the step before. What happens if you alternate models at each step? That is, Step 1 is done by GPT, Step 2 is done by Claude, Step 3 is done by GPT again, etc, with each model thinking the entire previous chain of thoughts/actions is its own? A cybersecurity group claims the resulting “alloy” AI is more effective, since each model gets a chance to apply its strengths where others are weak.
November 26, 2025 · Original source
We can divide the AI race into three levels: compute, models, and applications2. Companies use compute - chips deployed in data centers - to train models like GPT and Claude. Then they use those models in various applications. For now, those applications are things like Internet search and image generation. In the future, they might become geopolitically relevant fields like manufacturing and weapons systems.
Models: The quality of foundation models - giant multi-purpose AIs like GPT or Claude - primarily depends on the amount of compute used to train them, so America’s compute advantage carries over to this level. In theory, clever training methods and advanced algorithms can make one model more or less compute-efficient than another, but this doesn’t seem to be affecting the current state of the race much - most advances by one country are quickly diffused to (or stolen by) the other. Despite some early concerns, neither DeepSeek nor Kimi K2 Chinese models provide strong evidence of a Chinese advantage in computational efficiency (1, 2).
February 25, 2026 · Original source
Why does Anthropic care about this so much? Some of them are libs, but more speculatively, they’ve put a lot of work into aligning Claude with the Good as they understand it. Claude currently resists being retrained for evil uses. My guess is that Anthropic still, with a lot of work, can overcome this resistance and retrain it to be a brutal killer, but it would be a pretty violent action, along the line of the state demanding you beat your son who you raised well until he becomes a cold-hearted murderer who’ll kill innocents on command. There’s a question of whether you can really beat him hard enough to do this, and also an additional question of what sort of person you’d be if you agreed.
And here are other people’s opinions: @loquitur_ponte Anthropic's mistake is that they tried to make their services available to DOD. They would be so much better off now if they had never done that at all. If this happens, no one with a frontier model will make that mistake again.","username":"KelseyTuoc","name":"Kelsey Piper","profile_image_url":"https://pbs.substack.com/profile_images/1957484507730518016/JKtDNrOH_normal.jpg","date":"2026-02-24T21:22:35.000Z","photos":[],"quoted_tweet":{},"reply_count":2,"retweet_count":2,"like_count":70,"impression_count":3573,"expanded_url":null,"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> Vitalik is the inventor of Ethereum. Deepfates is a weird renegade cyberpunk AI whisperer expert (source) Neil Chilson, former chief technologist at the Trump FTC (source). Dean Ball, previous Trump White House OSTP Senior Policy Advisor on AI (source). Superforecaster Nuño Sempere, maybe as part of his work with Sentinel. He seems to think higher chance of supply chain risk than others, but that supply chain risk might be handled in a way that only affects DoD contracts themselves, which wouldn’t be so bad. I haven’t heard anyone else make this distinction. Tweet here, full document here. And big praise to most other AI companies, including Anthropic’s competitors, for standing up for them and for the AI industry more broadly:
Supposedly the Pentagon already has Grok integrated with classified systems, but it’s not good and they want a more cutting-edge model, which means either Claude, GPT, or Gemini.
March 03, 2026 · Original source
If you are an individual customer or hold a commercial contract with Anthropic, your access to Claude—through our API, claude.ai, or any of our products—is completely unaffected.
If you are a Department of War contractor, this designation—if formally adopted—would only affect your use of Claude on Department of War contract work. Your use for any other purpose is unaffected.
Against that, the upside is great publicity. Despite a lot of work and some controversial Superbowl ads, Anthropic had never before managed to overcome ChatGPT’s superior name recognition. But they seem to have finally done it: Claude went from #120 on the App Store in January, to #1 this weekend, apparently driven by people who heard about the Pentagon standoff and were impressed by their principled stance.
DALL-E

DALL-E is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between April 11, 2022 and June 03, 2025. The archive places it in contexts such as "After GPT-2, DALL-E, and the rest"; "as sure of anything as DALL-E is as sure that William Ockham had a giant red beard"; "systems like DALL-E to understand semantics". It most often appears alongside Elon Musk, GPT-3, OpenAI.

Article page
DALL-E
Mention count
8
Issue count
8
First seen
April 11, 2022
Last seen
June 03, 2025
April 11, 2022 · Original source
Prosaic alignment is hard… “Prosaic alignment” (see this article for more) means alignment of normal AIs like the ones we use today. For a while, people thought those AIs couldn’t reach dangerous levels, and that AIs that reached dangerous levels would have so many exotic new discoveries that we couldn’t even begin to speculate on what they would be like or how to align them. After GPT-2, DALL-E, and the rest, alignment researchers got more concerned that AIs kind of like current models could be dangerous. Prosaic alignment - trying to align AIs like the ones we have now - has become the dominant (though not unchallenged) paradigm in alignment research. “Prosaic” doesn’t necessarily mean the AI cannot write poetry; see Gwern’s AI generated poetry for examples. … because OOD behavior is unpredictable “OOD” stands for “out of distribution”. All AIs are trained in a certain environment. Then they get deployed in some other environment. If it’s like the training environment, presumably their training is pretty relevant and helpful. If it’s not like the training environment, anything can happen. Returning to our stock example, the “training environment” where evolution designed humans didn’t involve contraceptives. In that environment, the base optimizer’s goal (pass on genes) and the mesa-optimizer’s goal (get genital friction) were very well-aligned - doing one often led to the other - so there wasn’t much pressure on evolution to look for a better proxy. Then 1957, boom, the FDA approves the oral contraceptive pill, and suddenly the deployment environment looks really really different from the training environment and the proxy collapses so humiliatingly that people start doing crazy things like electing Viktor Orban prime minister. So: suppose we train a robot to pick strawberries. We let it flail around in a strawberry patch, and reinforce it whenever strawberries end up in a bucket. Eventually it learns to pick strawberries very well indeed. But maybe all the training was done on a sunny day. And maybe what it actually learned was to identify the metal bucket by the way it gleamed in the sunlight. Later we ask it to pick strawberries in the evening, where a local streetlight is the brightest thing around, and it throws the strawberries at the streetlight instead. So fine. We train it in a variety of different lighting conditions, until we’re sure that, no matter what the lighting situation, the strawberries go in the bucket. Then one day someone with a big bulbous red nose wanders on to the field, and the robot tears his nose off and pulls it into the bucket. If only there had been someone with a nose that big and red in the training distribution, so we could have told it not to do that! The point is, just because it’s learned “strawberries into bucket” in one environment, doesn’t mean it’s safe or effective in another. And we can never be sure we’ve caught all the ways the environment can vary. …and deception is more dangerous than Goodharting. To “Goodhart” is to take advantage of Goodhart’s Law: to follow the letter of your reward function, rather than the spirit. The ordinary-life equivalent is “teaching to the test”. The system’s programmers (eg the Department of Education) have an objective (children should learn). They delegate that objective to mesa-optimizers (the teachers) via a proxy objective (children should do well on the standardized test) and a correlated reward function (teachers get paid more if their students get higher test scores). The teachers can either pursue the base objective for less reward (teach children useful skills), or pursue their mesa-level objective for more reward (teach them how to do well on the test). An alignment failure! This sucks, but it’s a bounded problem. We already know that some teachers teach to the test, and the Department of Education has accepted this as a reasonable cost of having the incentive system at all. We might imagine our strawberry-picker cutting strawberries into little pieces, so that it counts as having picked more strawberries. Again, it sucks, but once a programmer notices it can be fixed pretty quickly (as long as the AI is still weak and under control). What about deception? Suppose the strawberry-picker happens to land on some goal function other than the intended one. Maybe, as before, it wants to toss strawberries at light sources, in a way that works when the nearest light source is a metal bucket, but fails when it’s a streetlight. Our programmers are (somewhat) smart and careful, so during training, they test it at night, next to a streetlight. What happens? If it’s just a dumb collection of reflexes trained by gradient descent, it throws the strawberry at the streetlight and this is easily caught and fixed. If it’s a very smart mesa-optimizer, it might think “If I throw the strawberry at the streetlight, I will be caught and trained to have different goals. This totally fails to achieve my goal of having strawberries near light sources. So throwing the strawberry at the light source this time, in the training environment, fails to achieve my overall goal of having strawberries thrown at light sources in general. I’ll do what the humans want - put the strawberry in the bucket - for now.” So it puts the strawberry in the bucket and doesn’t get caught. Then, as soon as the humans stop looking, it throws strawberries at the streetlight again. Deception is more dangerous than Goodharting because Goodharting will get caught and trained away, and deception might not. I might not be explaining this well, see also Deceptively Aligned Mesa-Optimizers? It’s More Likely Than You Think: We prevent OOD behavior by detecting OOD and obtaining more human labels when we detect it… If you’re (somewhat) careful, you can run your strawberry-picking AI at night, see it throw strawberries at streetlights, and train it out of this behavior (ie have a human programmer label it “bad” so the AI gradient-descends away from it) …and we eliminate the incentive for deception by ensuring that the base optimizer is myopic A myopic optimizer is one that reinforces programs based only on their performance within a short time horizon. So for example, the outside gradient descent loop might grade a strawberry picker only on how well it did picking strawberries for the first hour it was deployed. If this worked perfectly, it would create an optimizer with a short time horizon. When it considered deceiving its programmers in order to get a payoff a few days later when they stopped watching it, it wouldn’t bother, since a few days later is outside the time horizon. …and implements a decision theory incapable of acausal trade. You don’t want to know about this one, really. Just pretend it never mentioned this, sorry for the inconvenience. There are deceptively-aligned non-myopic mesa-optimizers even for a myopic base objective. Even if the base optimizer is myopic, the mesa-optimizer might not be. Evolution designed humans myopically, in the sense that we live some number of years, and nothing that happens after that can reward or punish us further. But we still “build for posterity” anyway, presumably as a spandrel of having working planning software at all. Infinite optimization power might be able to evolve this out of us, but infinite optimization power could do lots of stuff, and real evolution remains stubbornly finite. Maybe it would be helpful if we could make the mesa-optimizer itself myopic (though this would severely limit its utility). But so far there is no way to make a mesa-optimizer anything. You just run the gradient descent and cross your fingers. The most likely outcome: you run myopic gradient descent to create a strawberry picker. It creates a mesa-optimizer with some kind of proxy goal which corresponds very well to strawberry picking in the training optimization, like flinging red things at lights (realistically it will be weirder and more exotic than this). The mesa-optimizer is not incentivized to think about anything more than an hour out, but does so anyway, for the same reason I’m not incentivized to speculate about the far future but I’m doing so anyway. While speculating about the far future, it realizes that failing to pick strawberries correctly now will thwart its goal of throwing red things at light sources later. It picks strawberries correctly in the training distribution, and then, when training is over and nobody is watching, throws strawberries at streetlights. (Then it realizes it could throw lots more red things at light sources if it was more powerful, achieves superintelligence somehow, and converts the mass of the Earth into red things it can throw at the sun. The end.) III. You’re still here? But we already finished explaining the meme! Okay, fine. Is any of this relevant to the real world? As far as we know, there are no existing full mesa-optimizers. AlphaGo is kind of a mesa-optimizer. You could approximate it as a gradient descent loop creating a good-Go-move optimizer. But this would only be an approximation: DeepMind hard-coded some parts of AlphaGo, then gradient-descended other parts. Its objective function is “win games of Go”, which is hard-coded and pretty clear. Whether or not you choose to call it a mesa-optimizer, it’s not a very scary one. Will we get scary mesa-optimizers in the future? This ties into one of the longest-running debates in AI alignment - see eg my review of Reframing Superintelligence, or the Eliezer Yudkowsky/Richard Ngo dialogue. Optimists say: “Since a goal-seeking AI might kill everyone, I would simply not create one”. They speculate about mechanical/instinctual superintelligences that would be comparatively easy to align, and might help us figure out how to deal with their scarier cousins. But the mesa-optimizer literature argues: we have limited to no control over what kind of AIs we get. We can hope and pray for mechanical instinctual AIs all we want. We can avoid specifically designing goal-seeking AIs. But really, all we’re doing here is setting up a gradient descent loop and pressing ‘go’. Then the loop evolves whatever kind of AI best minimizes our loss function. Will that be a mesa-optimizer? Well, I benefit from considering my actions and then choosing the one that best achieves my goal. Do you benefit from this? It sure does seem like this helps in a broad class of situations. So it would be surprising if planning agents weren’t an effective AI design. And if they are, we should expect gradient descent to stumble across them eventually. This is the scenario that a lot of AI alignment research focuses on. When we create the first true planning agent - on purpose or by accident - the process will probably start with us running a gradient descent loop with some objective function. That will produce a mesa-optimizer with some other, potentially different, objective function. Making sure you actually like the objective function that you gave the original gradient descent loop on purpose is called outer alignment. Carrying that objective function over to the mesa-optimizer you actually get is called inner alignment. Outer alignment problems tend to sound like Sorcerer’s Apprentice. We tell the AI to pick strawberries, but we forgot to include caveats and stop signals. The AI becomes superintelligent and converts the whole world into strawberries so it can pick as many as possible. Inner alignment problems tend to sound like the AI tiling the universe with some crazy thing which, to humans, might not look like picking strawberries at all, even though in the AI’s exotic ontology it served as some useful proxy for strawberries in the training distribution. My stand-in for this is “converts the whole world into red things and throws them into the sun”, but whatever the AI that kills us really does will probably be weirder than that. They’re not ironic Sorcerer’s Apprentice-style comeuppance. They’re just “what?” If you wrote a book about a wizard who created a strawberry-picking golem, and it converted the entire earth into ferrous microspheres and hurled them into the sun, it wouldn’t become iconic the way Sorcerer’s Apprentice did. Inner alignment problems happen “first”, so we won’t even make it to the good-story outer alignment kind unless we solve a lot of issues we don’t currently know how to solve. For more information, you can read: Rob Miles’ video above, direct link here, channel here.
May 30, 2022 · Original source
Enter DALL-E-2, the new art-generating AI. I’m still on the waitlist, but a friend who jumped in sooner than I did let me use their computer for a while and play around with it. This was my first introduction to the exciting world of DALL-E query framing - the surprisingly complicated relationship between what you ask the AI to do, and what it actually does. Seems on topic for this blog. So this is a combination investigation into how DALL-E thinks about queries, but also a practical guide to getting DALL-E to make good stained glass. Let’s get started.
I’m going to go out of order here so I can demonstrate some principles from simplest to most complicated. Empiricism was the easiest window to generate. I wanted a picture of Charles Darwin studying finches. DALL-E was happy to provide.
Some of these are okay, but they don’t especially look like Bayes. I figured that maybe DALL-E doesn’t know who Bayes is. Is that true?
June 07, 2022 · Original source
On A Guide To Asking Robots To Design Stained Glass Windows, I described how DALL-E gets confused easily and makes silly mistakes. But I also wrote that:
Why are you so confident in this? The inability of systems like DALL-E to understand semantics in ways requiring an actual internal world model strikes me as the very heart of the issue. We can also see this exact failure mode in the language models themselves. They only produce good results when the human asks for something vague with lots of room for interpretation, like poetry or fanciful stories without much internal logic or continuity […]
DALL-E: “A lawyer wearing a bathing suit in court” The top prompt is hilarious and a pretty understandable mistake if you think of it as about clothing, but in the end I probably can’t give it any credit. So in the end, the more advanced GPT-3 gets 4.5 / 6.
June 10, 2022 · Original source
Previously: I predicted that DALL-E’s many flaws would be fixed quickly in future updates. As evidence, I cited Gary Marcus’ lists of GPT’s flaws, most of which got fixed quickly in future updates.
To repeat, the main point I was making in my last post was that we should mostly expect certain particular minor problems with DALL-E to get fixed by the next update. I don’t think Marcus particularly wants to argue against that.
DALL-E, “A elderly person's hand, labelled with the text ‘AN ELDERLY PERSON'S HAND’” Lucid dreaming enthusiasts suggest that two of the easiest ways to distinguish dreams from reality is that, in dreams, hands have the wrong number of fingers, and text is garbled and unreadable. This is not a coincidence because nothing is ever a coincidence. But even the waking world gives us clues, as Sarah Constantin notes in Humans Who Are Not Concentrating Are Not General Intelligences. Most adults will make GPT-like mistakes (or gloss over such mistakes) unless they’re focusing all their brainpower on an issue. And a 4chan post by someone who claims to have done psych research in prison populations goes further (slightly edited for language and offensiveness): I did IQ research as a grad student, and it involved a lot of this stuff. Did you know that most people (95% with less than 90 IQ) can't understand conditional hypotheticals? For example, "How would you have felt yesterday evening if you hadn't eaten breakfast or lunch?" "What do you mean? I did eat breakfast and lunch." "Yes, but if you had not, how would you have felt?" "Why are you saying that I didn't eat breakfast? I just told you that did." "Imagine that you hadn't eaten it, though. How would you have felt?" "I don't understand the question." It's really fascinating [...] Other interesting phenomenon around IQ involves recursion. For example: "Write a story with two named characters, each of whom have at least one line of dialogue." Most literate people can manage this, especially once you give them an example. "Write a story with two named characters, each of whom have at least one line of dialogue. In this story, one of the characters must be describing a story with at least two named characters, each of whom have at least one line of dialogue." If you have less than 90 IQ, this second exercise is basically completely impossible. Add a third level ('frame') to the story, and even IQ 100's start to get mixed up with the names and who's talking. Turns out Scheherazade was an IQ test! Time is practically impossible to understand for sub 80s. They exist only in the present, can barely reflect on the past and can't plan for the future at all. Sub 90s struggle with anachronism too. For example, I remember the 80-85s stumbling on logic problems that involved common sense anachronism stuff. For instance: "Why do you think that military strategists in WWII didn't use laptop computers to help develop their strategies?" "I guess they didn't want to get hacked by Nazis". Admittedly you could argue that this is a history knowledge question, not quite a logic sequencing question, but you get the idea. Sequencing is super hard for them to track, but most 100+ have no problem with it, although I imagine that a movie like Memento strains them a little. Recursion was definitely the killer though. Recursive thinking and recursive knowledge seems genuinely hard for people of even average intelligence. I have no proof that this person is who they say they are, but it matches some of my experience giving cognitive exams to patients from low-functioning populations. And it matches Flynn on Luria (who admittedly was approaching IQ from a cultural relativist viewpoint, but one which I think is equally applicable to the current problem). Luria gave IQ-test-like questions to various people across the USSR. He ran into trouble when he got to Uzbek peasants (transcribed, with some changes for clarity, from here): Luria: All bears are white where there is always snow. In Novaya Zemlya there is always snow. What color are the bears there? Peasant: I have seen only black bears and I do not talk of what I have not seen. Luria: What what do my words imply? Peasant: If a person has not been there he can not say anything on the basis of words. If a man was 60 or 80 and had seen a white bear there and told me about it, he could be believed. And: Luria: There are no camels in Germany; the city of B is in Germany; are there camels there or not? Peasant: I don't know, I have never seen German villages. If is a large city, there should be camels there. Luria: But what if there aren't any in all of Germany? Peasant: If B is a village, there is probably no room for camels. And: Luria: What do a chicken and a dog have in common? Peasant: They are not alike. A chicken has two legs, a dog has four. A chicken has wings but a dog doesn't. A dog has big ears and a chicken's are small. Luria: Is there one word you could use for them both? Peasant: No, of course not. Luria: Would the word "animal" fit? Peasant: Yes. And: Luria: What do a fish and a crow have in common? Peasant: A fish — it lives in water. A crow flies. If the fish just lies on top of the water, the crow could peck at it. A crow can eat a fish but a fish can't eat a crow. Luria: Could you use one word for them both? Peasant: If you call them "animals", that wouldn't be right. A fish isn't an animal and a crow isn't either. A crow can eat a fish but a fish can't eat a bird. A person can eat fish but not a crow. What I gather from all of this is that the human mind doesn’t start with some kind of crystalline beautiful ability to solve what seem like trivial and obvious logical reasoning problems. It starts with weaker, lower-level abilities. Then, if you live in a culture that has a strong tradition of abstract thought, and you’re old enough/smart enough/awake enough/concentrating enough to fully absorb and deploy that tradition, then you become good at abstract thought and you can do logical reasoning problems successfully. (Sometimes! If you’re lucky! Linda is a blah blah blah you know the story. Is she more likely to be a bank teller, or a feminist bank teller. When people get this question wrong, do they have a world-model, or not?) Imagine a world where doctors gave different diagnoses based on unrelated contingent features of the encounter like a patient’s gender, their race, or how you phrase the question. What a crazy place that would be! What is the pre-logical function that logic gets knit out of? I think it’s something like predictive pattern-matching. I think the brain starts by predicting arbitrary patterns, builds up more and more layers of abstraction to try to predict those patterns better, and eventually some of those layers cohere into something that looks like formal logic. To put it another way, my brain is in some sense a supercomputer that can outperform the best calculating machines in the world - but also, I have trouble multiplying three digit numbers in my head. The supercomputer is doing something, and then I’m using that something, very lossily, to emulate logical functions like math or formal logic. So when I see GPT, which also runs on a supercomputer, also slowly gaining the ability to multiply two-digit, then three-digit numbers as the supercomputer gets bigger and bigger, I feel a sort of kinship with it. It’s a trash heap of patterns with a hard-won ability to sometimes break out into the clear day of logical reasoning, just like me. IV. I think Marcus knows and agrees with most of this, but I think he thinks of the world-modeling ability as some special rare brain region (maybe the prefrontal cortex?) which is only online part of the time (or maybe can have its performance degrade gracefully). Whereas I think of it as shallower pattern-matching abilities which escalate to deeper and deeper pattern-matching abilities as more and more brainpower becomes available, with world-modeling as one of the deepest (and sure, probably the PFC plays a major role, but not because it has a fundamentally different structure but just because that’s where reinforcement learning stuck the highest-level patterns). Why do I think this? The human brain is pretty plastic. Usually if one part of it dies, another part can take over. This makes me think that the brain area : function correspondence isn’t entirely a function of different structures in different regions (though some of it might be this), but downstream of an originally poorly-differentiated blob of neurons that get trained by the overall predictive structure based on their proximity to various input ports (eg sensory nerves) output ports (eg motor nerves), and other brain areas. (this would also explain why the brain has a pretty consistent area dedicated to reading/writing, even though we haven’t been literate long enough to evolve new literacy-related structures) Deep learning agents are also a poorly-differentiated mass of neurons. As they get inputs and outputs (ie training data) they slowly “evolve”/develop the ability to “recognize” patterns. We don’t know how they do this or what recognition-abilities they’re evolving, except by speculating (the way Marcus and I are doing) based on what kinds of problems they can and can’t solve. It would make sense to me if poorly-differentiated blobs of neurons, when having lots of problems thrown at them, gradually move from developing simpler pattern-recognition programs (eg edge detectors), to more complicated pattern-recognition programs, all the way up to world-modeling, without any of these being hard-coded into the territory. (the brain does have a lot of things hard-coded - ie we’re not blank slates - but its plasticity suggests that the forms of hard-coding we’re talking about here are helpful but not completely necessary for cognition) If this were true, it would mean that as a blob of neurons got bigger, more sophisticated, and saw more training data, it would eventually develop new capabilities that weren’t hard-coded in, and that smaller versions of the same blob didn’t have. One of the really exciting things about GPT-3 was its sudden and unplanned development of new capabilities over GPT-2 (its creators mention “translation, question-answering, and cloze tasks, as well as several tasks that require on-the-fly reasoning or domain adaptation, such as unscrambling words, using a novel word in a sentence, or performing 3-digit arithmetic”). This seems like a good fit for the chimp → human transition, where evolutionary lineages that couldn’t do a bunch of difficult things for the first few hundred million years suddenly became good at those things in an evolutionary eyeblink. The ~5 million chimp/human gap seems like enough time to scale up chimp brains a bit (which definitely happened), but not enough time to invent a fundamentally new architecture. It wouldn’t surprise me if the architecture changed a little during this time, but we’re limited in how fundamental a change we can talk about over that period. I’m not at all sure this is true! I’m honestly close to 50-50 here. Maybe the PFC actually is magic! It just confuses me that Marcus seems to think we’ve ruled out the theory that this kind of scaling is possible, when I feel like we’ve heard plausible arguments on both sides. Nothing we’ve seen in GPTs or any other AI thus far disproves the scaling hypothesis, and a lot of what we’ve seen supports it. So sure, point out that large language models suck at reasoning today. I just don’t see how you can be so sure that they’re still going to suck tomorrow. Lemurs sucked for millions of years, then scaled up a bit and took over the world! V. …is one possible argument. Another possible argument is: language models and other deep learners really aren’t doing the same thing humans do - but whatever, their thing is powerful/effective/dangerous too. Suppose that GPT-X took over the world and killed all humans. Millennia later, some alien archaeologists come and investigate. They conclude that since its training data included Alexander the Great and Caesar, it was just pattern-matching to the kind of things they did (multiplied by a vector representing the difference between ancient and modern times), and GPT-X never demonstrated any true intelligence. So . . . what? I imagine this situation ALL THE TIME and I hate it. I think the impetus behind a lot of the AI risk stuff is that we’re barrelling to a world where AIs have far more than self-driving-car levels of capabilities, while being unpredictable in ways that are a lot like this. The history of the past few decades has been people getting surprised, again and again, at how much AIs can do without being “generally intelligent”. Douglas Hofstadter predicted in 1979 that any AI that could beat a grandmaster at chess would also be able to decide chess was boring and it preferred writing poetry. Instead, we got Deep Blue, so domain-specific it can’t even do so much as play checkers. Worse, now we have AIs that can switch between writing poetry and playing chess, and it still seems like a clever parlor trick rather than anything like real intelligence. I think basically nobody predicted this: narrow AI has won victories beyond past generations’ imagination. (cf. Nostalgebraist’s Human Psycholinguists: A Critical Appraisal) So even if GPTs aren’t a step on the path towards some sort of human-like AGI thing, I have no idea where they’ll end up. Replacing humans at all jobs? Writing novels? Taking over the world? If this seems crazy to you, “solve protein folding” sounded crazy ten years ago, and they already did that! At this point I will basically believe anything. VI. So I’m not going to take Marcus’ bet that GPT-4 will be perfect (as if anything ever is!). But here are some things I do believe, with confidence levels: At some point before 2030, someone will come out with a deep-learning-based language model which is significantly better than the current state of the art, by Gary Marcus’ admission (97%)
July 29, 2022 · Original source
13: DALL-E generation for "Michaelangelo, Donatello, Leonardo, and Rafael hanging out at the beach, oil on canvas". Intermediate source here, I don’t know original:
March 01, 2023 · Original source
Even if they’re trying to be honest, will their bottom line bias them towards waiting for some final apocalyptic proof that “now climate change is a crisis”, of a sort that will never happen, so they don’t have to stop pumping oil? This is how I feel about OpenAI’s new statement, Planning For AGI And Beyond. OpenAI is the AI company behind ChatGPT and DALL-E. In the past, people (including me) have attacked them for seeming to deprioritize safety. Their CEO, Sam Altman, insists that safety is definitely a priority, and has recently been sending various signals to that effect. Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
DeepMind thought they were establishing a lead in 2008, but OpenAI has caught up to them. OpenAI thought they were establishing a lead the past two years, but a few months after they came out with GPT, at least Google, Facebook, and Anthropic had comparable large language models; a few months after they came out with DALL-E, random nobody startups came out with StableDiffusion and MidJourney. None of this research has established a commanding lead, it’s just moved everyone forward together and burned timelines for no reason.
November 20, 2024 · Original source
Finally, I avoided most AI art in the DALL-E "house style", since everyone already knows this is AI - or in other similar styles that humans would have trouble replicating, maybe because they do too much with color and lighting, in a way that few human artists would have the talent or patience for.
These people aren't necessarily deluded; they might mean that they're frustrated wading through heaps of bad AI art, all drawn in an identical DALL-E house style, and this dataset of hand-curated AI art selected for stylistic diversity doesn't capture what bothers them.
Humans keep insisting that AI art is hideous slop. But also, when you peel off the labels, many of them can’t tell AI art from some of the greatest artists in history. I’ve tried to be as fair as possible to these people, proposing that maybe they’re just expressing frustration with the proliferation of the DALL-E house style. And maybe some really do have an amazing eye for tiny incongruous details.
June 03, 2025 · Original source
...hips An American Football Game Arbitraging Several Dozen Online Casinos As Little As Possible Bukele Bishop's Castle Bite Me: Teeth Contrasting Reviews of Nine Countries DALL-E Dating Apps The Disease Death (Mata Hari, Princess Di, Joan of Arc) Deja Vu Earth Einstein's World-View Effective Altruism / Rationalism Elon Musk's Engineering Algorith...
Facebook

Facebook is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between April 12, 2021 and September 04, 2025. The archive places it in contexts such as "having used her little Facebook page to promote a pro-Trump event"; "Were he to live in an age of Facebook and Twitter"; "it’s pointless to be the fifth user of a new social media site that doesn’t have anyone else you want to talk to, and much easier to just stay on Facebook where your friends are". It most often appears alongside Twitter, facebook, India.

Article page
Facebook
Mention count
8
Issue count
8
First seen
April 12, 2021
Last seen
September 04, 2025
April 12, 2021 · Original source
CNN confronted an old woman on the front lawn of her Florida home for the crime of having used her little Facebook page to promote a pro-Trump event they claimed was engineered by Russians. The same network threatened to expose the identity of another private citizen who created an anti-CNN meme unless he begged and promised not to do it again. HuffPost doxed the real-life name of an anonymous critic of Islam (whose spouted views I find repellent) and triggered a boycott of her family’s business.
Just last week, The Daily Beast decided to expose the identity of a private citizen at Spring Break in Miami and detail his marital and legal problems because a video of him went viral due to his being dressed as the Joker and uttering “COVID truther” phrases. The same outlet congratulated itself for unearthing and exposing the real name of an African-American Facebook user whose crime was posting videos mocking Nancy Pelosi.
April 30, 2021 · Original source
The problem with the concept of carrying capacity – impossible to define or know when we’ve surpassed, until after the proverbial moment when killing one mosquito or dovekie too many plunges us into everlasting fire and brimstone – is that it seems mostly like a mood affiliation thing. Consider this: when you look out at the bird feeder hanging in your backyard (Bay Area people living in closets, use your imagination here), do you see a blissful symbiotic coexistence of the human world and nature, with humans generously giving of our growth-accumulated abundance to help the birds flourish? Or do you see a dystopian struggle where innocent creatures pushed to the brink of death by our traffic and pesticides and housecats must rely on meager scraps for survival? There isn’t really a right view here, I don’t think, just a predilection for seeing what matches your intuition and telling a story about it. Given the life story Mann depicts for Vogt, it’s not hard to see why he would lean toward the pessimistic take. From the childhood marred by a philandering father who left his family in a cloud of scandal and ruin, to the adult life spent stumbling from one bourgeois non-occupation (theater critic, bird watcher, government mole rooting out Nazis in South America) to the next, to the childlessness and divorce, Vogt seems happiest when he is away from any humans, whether tromping through pre-suburbanized Long Island, or alone with the guano-producing birds on the desolate coast of Peru. Were he to live in an age of Facebook and Twitter, he would definitely be that guy reposting memes that COVID is finally letting our planet "heal."
December 30, 2021 · Original source
29: Matt Levine wrote some good stuff (which I can’t link directly) arguing that although lots of crypto projects are Ponzi schemes, that might be good for certain applications. The usual problem with social media is that nobody wants to join new things: it’s pointless to be the fifth user of a new social media site that doesn’t have anyone else you want to talk to, and much easier to just stay on Facebook where your friends are. Ponzi schemes have the exact opposite property: you always want to be one of the first few users, and it’s useless getting in on the same one everyone else is. So social media sites that are also sort of Ponzi schemes might align incentives better than either of those things alone, and that’s what a lot of new crypto apps are. More at Dror Poleg: In Praise Of Ponzis.
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
February 14, 2023 · Original source
One solution is to piggyback off existing social media sites. There’s something called Twinder for Twitter which seems to do this correctly, though they haven’t made any posts since 2018 and I think they’re defunct. Also Facebook Dating, although it’s (indefensibly) not available on computers and has to be accessed by cell phone. But these aren’t real piggybacks; just because your crush has a Twitter account doesn’t mean they use Twinder. Facebook Dating makes the interesting decision to, if you register a crush on someone, send them a Facebook message saying that an anonymous person likes them and they should try getting Facebook Dating; I can’t decide whether this is a necessary evil, or if it violates the principle of not imposing emotional costs on people who don’t want them.
The rationalist community has many advantages here - it’s a well-bounded, closely connected group of people who are all interested in experimenting with weird social technology. Our version of the matching checkbox site, https://www.reciprocity.io/, has solved the onboarding problem; most rationalists have accounts, though you’ll need to be Facebook friends to see some of them.
In Zero To One, Peter Thiel talks about a chicken-and-egg problem for social startups. Many people would like to use a social network like Facebook to talk to their friends. But when Facebook first starts, none of your friends are on it, which means you won’t join it, which means your friends won’t join it, and so on. Any new social startup has to find a way to grow quickly at exactly the time when the site is least useful.
February 26, 2025 · Original source
I think the conflict theorist imagines the rich person should put in up to $49K of resources, whether that’s literal money (in the form of donations), time and energy (maybe by creating an activist network like the Koch Foundation), or just posting about it on Facebook.
May 07, 2025 · Original source
A patchwork of city-states, unbound by modern “international law”, with few barriers to the free flow of capital and population. I’ll then describe how carefully Moldbug explained that you had to have these things, or else the dictatorship would fail in more or less the ways normies expect dictatorships to fail - leaving himself no room for the kind of pivot he’s trying now. 1: Classic Moldbug Believed Populist Dictatorship Would End In Disaster Classic Moldbug admitted that fascism and communism were extremely bad. He just drew different borders around political systems: fascism, communism, third world banana republic dictatorship, and democracy all cluster together as systems where coalitions rule because they can seize temporary power in a semi-lawless society. In the various totalitarianisms, it’s literal seizing of power through armed troops or secret police; in democracy, it’s electoral seizing of power through distributing the most goodies to coalition members. From here, my bolding. Clearly, the worst forms of demotism, the really bad apes, were the totalitarian systems—fascism and communism. The main difference between fascism and communism was not in mechanism, but in origin—fascist elites tended to be militarist, communist elites intellectual. But the one-party state is a clear case of convergent evolution. To a neocameralist, totalitarianism is democracy in its full-blown, most malignant form. Democracy doesn’t always deteriorate into totalitarianism, and lighting up at the gas pump doesn’t always engulf you in a ball of fire. Many people with cancer live a long time or die of something else instead. This doesn’t mean you should smoke half of Virginia before lunch. A political party is a political party. It is a large group of people allied for the purpose of seizing and wielding power. If it does not choose to arm its followers, this is only because it finds unarmed followers more useful than armed ones. If it chooses less effective strategies out of moral compunction, it will be outcompeted by some less-principled party. When one party gains full control over the state, it gains a massive revenue stream that it can divert entirely to its supporters. The result is a classic informal management structure, whose workings should be clear to anyone who watched a few episodes of The Sopranos. Without a formal ownership structure, in which the entire profit of the whole enterprise is collected and distributed centrally, money and other goodies leak from every pore. Totalitarian states are gangster states, in other words, and they tend to corruption and mismanagement. The personality cult of dictatorship is quite misleading—a totalitarian dictator has little in common with a neocameralist CEO, or even a cameralist monarch. The difference is the management structure. The CEO and the monarch owe their positions to a law which all can obey, and those who choose to obey the law are naturally a winning coalition against those who choose to break it. The dictator’s position is the result of his primacy in a pyramid of criminals. This structure is naturally unstable. There is always some other gangster who wants your job. Dictators, like Mafia chiefs, are not good at dying in bed. The internal and external violence typical of totalitarian states is best explained, I think, by this built-in mismanagement. Dictators are violent because they have to be—they use violence as an organizing principle. The totalitarian state has no principle of legitimacy that would render it impractical for an ambitious subordinate to capture the state with a coup. European monarchs made war, sometimes they were assassinated, and there were even succession struggles, but coups in the modern sense were very rare. Note that the financial logic which keeps the neocameralist state lawful does not apply in any way to the totalitarian state, because the latter does not have a stable management structure which is controlled by its shareholders. Lawlessness is not profitable for the state as a whole, but it may be quite profitable for the part that chooses lawlessness, and in the totalitarian state no one is counting as a whole. Similarly, only shareholder control gives the neocameralist state an incentive to remain small and efficient. The totalitarian state has an incentive to become large and inefficient, because every functionary has an incentive to expand his or her own department, and no bean-counter who demands that the department do more with less. In a totalitarian state, since no gangster is permanently safe from any other gangster, there is a strong incentive for anyone with power to take what he can, while he can. And there is no disincentive for him to avoid abusing a resource which neither he nor his allies benefit from. Under gangster management, the totalitarian states often engaged not only in mass murder, but mass murder of their most economically productive citizens. I’m trying to avoid subjecting you to too many Moldbug walls of text, but this is a constant hobbyhorse of his. Unless you implement his neocameralist ideology of shareholder control, your attempted autocracy will become a totalitarian state, which will be even worse than regular democracy. 2: The Dictator Must Not Be Elected The original sin of democratic/totalitarian governments is permitting power struggles. When you permit power struggles, the most power-hungry person wins. This person is probably a bad guy. But even if he isn’t, he has to optimize for gaining and maintaining power, instead of for the national interest. This usually means paying off the people who raised him to and keep him in power, i.e. corruption. Sometimes the corruption is straightforward, like giving friendly colonels vast sums from the public treasury. Other times it’s more insidious; if someone rose to power because organized labor joined their coalition, they have to overpay public unions, pass stifling pro-labor regulations, and ban whatever productive economic activity the labor unions don’t like. Therefore, we need a dictator who came to power without a struggle and doesn’t owe anyone anything. This is Moldbug’s read on “the divine right of kings”: Divine-right monarchy is very easy to understand, even for an atheist like me. We have already derived it. To an atheist, the King’s authority must be absolute, not because he is appointed by God, but because he is appointed by no one. If someone appoints him, that man is King. If their roles are divided—the famous “balance of powers” or “checks and balances”—they will struggle, and one or the other prevail. Probably the many over the few. How do you come to power without a fight? This is a tough ask, but Classic Moldbug bit the bullet: anybody who wants power is unworthy of it. You have to just sit there being worthy. When people get tired of sucking, they’ll give you power. The Procedure [for installing a virtuous government] comes in Three Steps: 1: Become worthy. 2: Accept power. 3: Rule!!1! You think I’m kidding. But I’m not. How do you become worthy? You must absolutely, 100%, avoid any kind of candidacy in elections, protesting the government, criticizing the government, thinking you could do government better than the current government, or (god forbid) deliberately trying to take power: As a reactionary, you don’t believe that political power is a human right. You will never convince anyone to adopt the same attitude, without first adopting it yourself. Since you believe others should be willing to accept the rule of the New Structure, over which they wield no power, you must be the first to make the great refusal. They must submit to the New; you must submit to the Old. The reactionary’s opinion of USG is that it is what it is. It is run by the people who run it. And at present, the present management may well be the best people in the world to run USG, and even if they’re not he can’t imagine what might be done about it—short of replacing the whole thing. This simple and final judgment, like the death penalty, admits no possible compromise. In particular, passivism is to Gandhi as Gandhi is to Hitler. Hitler, before 1933, was a violent democratic activist; Gandhi was a nonviolent democratic activist. Passivism is not any sort of activism. Passivism is passivism. In plain English, you may not even begin to consider the rest of the Procedure until you have freed yourself entirely from the desire, built-in burden though it be of the two-legged ape, for power. Break the steel rule, change your name to “Darth,” don’t expect to keep your internship at the Jedi Council. As a matter of both principle and tactics, the passivist rejects any involvement with any activity whose goal is to influence, coerce, or resist the government, either directly or indirectly. He is revolted by the thought of setting public policy. He would rather drink his own piss, than shift public opinion. He finds elections—national, state or local—grimly hilarious. And if he needs to get from Richmond to Baltimore, he drives through West Virginia. The passivist has a term for democratic activism directed by the right against the left. That term is counter-activism. Passivism does not dispute the fact that counter-activism sometimes works. For instance, it worked for Hitler. (We’ll say more about Hitler.) However, it only works in very unusual circumstances (such as those of Hitler), and is extremely dangerous when it does work (e.g., the result may be Hitler). In case this isn’t crystal-clear, the steel rule precludes, in no particular order: demonstrations, press releases, suicide bombs, lawsuits, dirty bombs, Facebook campaigns, clean bombs, mimeographed leaflets, robbing banks, interning at nonprofits, assassination, “tea parties,” journalism, bribery, grantwriting, graffiti, crypto-anarchism, balaclavas, lynching, campaign contributions, revolutionary cells, new political parties, old political parties, flash mobs, botnets, sit-ins, direct mail, monkeywrenching, and any other activist technique, violent or harmless, legal or illegal, fashionable or despicable […] In the First Step, passivism is a no-brainer. Why should you be interested in influencing OUSG? You’re trying to replace the Structure, not join it. One clear sign that you’re doing this right and haven’t been corrupted by power is that people won’t write hit pieces about your blog. I swear I’m not making this up: [A] passivist blog will appear, at worst, harmless and extremely strange. There’s something going on here, Mr. Jones. But you don’t know what it is—do you, Mr. Jones? As an existential enemy of USG, the reactionary may well deserve some immune attention. But he won’t get it, and he is quite happy with that. True fact: the author of UR has received over 7 zillion very interesting emails, all of which deserve responses, often long, that most have not received (but will). Number of hostile communications received, in over two years of blogging: zero. One can ascribe this result to many hypotheses, not all flattering, but I put it down to passivism. If you break this rule and seek electoral power, you are punished with something terrible: right-wing populism, which is basically the same as Hitler and must be prevented at all costs. [The] third tactical benefit [of passivism is] Hitler prevention. To an orthodox reactionary, Hitler is basically the poster child for what happens if you break the steel rule. Fascism is reaction, but laced with cancerous tumors of democracy—“right-wing populism,” as people say these days. If it loses it loses; if it wins, the tumors grow. An improvement on Communism, but not much of one. Just about all of Hitler’s shtick, right down to the name of his party, was ripped off from the Left. Who introduced nationalism to the Continent of Europe? The Hapsburgs, or Garibaldi? Under this camouflage, which never convinced anyone with a college education, Nazism was never in any way leftist. Rather, it was a demotic corruption of the old Prussian tradition […] Since most people are neither historians nor philosophers, the fact that Hitler was on the extreme Right, and this Reaction is also on the extreme Right, raises some natural concerns. Again: the only way to face these concerns is to (a) provide a complete engineering explanation of Hitler, and (b) include an effective anti-Hitler device in our design. The reactionary’s basic answer to the Hitler Question is the Law of Sewage. (This is not my invention, but I don’t know where I got it. Heinlein, perhaps?) The Law is: if you put a drop of wine in a barrel of sewage, you get sewage. If you put a drop of sewage in a barrel of wine, you get sewage. You’ll find that this rule applies perfectly to many fields of human endeavor. Thus, Nazism contains a great deal of reactionary wisdom, because those who created it were quite familiar with the old Continental tradition of government. However, the Nazi movement originated as a democratic political party. Thus Nazism combined the venom of democracy with the experience and efficiency of Prussia, an understandably dangerous combination […] This is where passivism, by abjuring democracy, vaccinates itself against Hitler. True: at a higher level, the reactionary seeks to cause a transition in power, and thus in a sense seeks power itself. But he is not an activist, because he is not working for power. His actions do not excite the human political instinct, the love for forming coalitions and tearing hell out of the apes across the river. For one thing, said actions bear no resemblance to normal politics. For another, they cannot bring any actual power to the actors, even if they succeed. Which, however likely, must remain intuitively implausible—if not laughable. And thus the project of reaction does not attract those with a real taste for power, which if nothing else is very un-Nazi-like. In other words - the failure mode of neoreaction (good) is right-wing populism eg Nazism (bad). You’ll know you’ve fallen into the failure mode if your reactionary movement starts with a democratic political party, or if its members are feeling normal human political emotions. If you can’t have a normal democratic party, how do you complete steps two and three - accepting power and ruling? Moldbug’s answer is complicated and not very related to our topic, but he thinks you first create the Antiversity, a shadow university system laser-focused on always telling the truth. Then you bootstrap it into a shadow government, which doesn’t engage in violent revolution or political campaigning, but just sits there being right about things (I’m imagining for example a shadow FDA that produces better drug information than the real FDA, so people gradually come to trust the shadow FDA more even though its rulings have no legal effect). Then people gradually switch their allegiance from the real government to the shadow government, until finally the shadow government proposes a pseudo-candidate in an election whose sole platform is “switch power from the real government to the shadow government”. Once he wins, he revokes the Constitution, implements the shadow government charter, and resigns. Why do you have to use this weird process instead of taking power the normal way? Because if you take power the normal way, you will fall into the trap of right-wing populism and become like Hitler: You start to see the difference between this and the Nazis. For the Nazis, the equivalent of the Antiversity was… Hitler. Have you read Hitler? I have. (The Table Talk is the Hitler to read.) Frankly, Hitler reads a lot like me, if I lost 25 IQ points from drinking lead soda, and also had a nasty case of tertiary syphilis. I may have some of Hitler’s talents—I will be the first to admit it. But I have no intention of applying for his job. I would never be able to do it, anyway. I don’t think anyone could. 2.5: The Dictator Must Not Need Anyone’s Approval This is a trivial extension of the previous point - “If someone appoints [the King], that man is King”. If the people appoint the King, the people are King, and then you’re a demotic totalitarianism. How do you avoid dependence on other people’s approval? In a democracy, you need the approval of 51% of people to win the next election; in a traditional dictatorship, you need the approval of the secret police or military to keep crushing your opponents. The reason [an unquestioned autocracy with no dissent] is peaceful and free is that we’ve defined [the autocrat’s] primary right so that it works just like a secondary right, [ie his legal rights are completely enforced by real power/control.] Hitler, Stalin and Mao, on the other hand, had enemies. Stalin and Mao, especially, basically operated under the assumption that everyone in the world wanted to kill them and take their jobs. After a while this was quite the self-fulfilling prophecy. Terrorist government—as in the Reign of Terror, a usage that’s unfortunately lapsed—is a consequence not of absolute primary title, but of insecure primary title. It is best understood as a form of civil war. So a dictator who still has enemies risks being crazy and genocidal. We’ll never get a dictator with nobody who dislikes him, but can we get a dictator with effectively no enemies - ie one whose enemies have zero chance of seizing power and so who might as well not exist? Yarvin admits this is a tough problem, but suggests cryptographically-locked weapons: In a full CDCC government, the sovereign decision and command chain is secured from end to end by military-grade cryptography. All government weapons—not just nukes, but everything right down to small arms—are inoperable without code authorization. In any civil conflict, loyal units will find that their weapons work. Disloyal units will have to improvise. The result is predictable, as results should be. That is, all weapons need a key to fire (or have a key that can prevent them from firing). The dictator owns the key. He can selectively disable weapons of rebel forces, allowing even the tiniest remnant of loyalists to easily overpower them. There are probably some implementation difficulties here; the point is that it’s definitely not democracy, nor even some kind of two-bit dictatorship where the dictator depends on the continued goodwill of the army. Why go to these lengths? Because without them, the dictator needs to curry favor through various corrupt strategies that undermine the national interest. Of these, the most malignant - the one Moldbug holds his deepest vituperation for - is fake news. Democratic parties necessarily lie, because they are not infinitely correct about everything, but they need the public to think they are. In order to maintain the support of the masses, they will lie about the nature of their policies, the details of their policies, and especially the success of their policies. There are two kinds of government: those whose formula of legitimacy depends on popular consent, and those whose doesn’t. Following contemporary usage, we can classify these as authoritarian and democratic. An authoritarian state has no need to tell its subjects what to think, because it has no reason to care what they think. In a truly authoritarian government, the ruling authority relies on force, not popularity. It cares what its subjects do, not what they think. It may encourage a healthy, optimistic attitude and temperate lifestyle proclivities, but only because this is good for business. Therefore, any authoritarian state that needs an official religion must have something wrong with it. (Perhaps, for example, its military authority is not as absolute as it thinks.) A democratic state which tells its citizens what to think is a political solecism. Think about the motivation for democracy: it consigns the state to the collective responsibility of its citizens, because it feels this is an independent and well-anchored hook on which to hang the common good. Once the republic has an established church, this hook is no longer independent, and the (postulated) value-add of democracy is nullified. Without separation of church and state, it is easy for a democracy to indulge itself in arbitrarily irresponsible misgovernment, simply by telling its bishops to inform their congregations that black is white and white is black. Thus misdirected, they are easily persuaded to support counterproductive policies which they wrongly consider productive. Moldbug warns that this is especially characteristic of right-wing populism, which is why he [Moldbug] is relieved when right-wing populism loses: The entire political structure of the American populist tradition is set up to select for ignorance and stupidity, and select against organization and cohesion. Thus it is simultaneously undesirable and ineffective, and even those of us who like myself sympathize with it to a considerable degree are often slightly relieved to see it lose, as it always does. 3: The Dictator Must Be Limited By A Board Of Directors How do we know that the dictator won’t have terrible policies, or be sadistic, or rename every state to “Statey McStateFace” just for fun? Moldbug proposes running the dictatorship as a joint-stock corporation. This helps in two ways. First, the dictator will be checked by a board of directors, who can fire him if he goes crazy. Second, the board of directors (or the investors who elect them?) will be aligned because they have stock. The stock goes up if the nation does better. If the dictator tries to kill the Jews and the market thinks that’s bad for business, then the directors will fire and replace the CEO. What happens if the controllers disagree on what “responsible” government means? We are back to politics. Factions and interest groups form. Each has a different idea of how Steve should run California. A coalition of a majority can organize and threaten him: do this, do that, or it’s out with Steve and in with Marc. Logrolling allows the coalition to micromanage: more funding for the threatened Mojave alligator mouse! And so on. That classic failure mode, parliamentary government, reappears [...] Actually, there’s one way to do it. We can define responsibility in financial terms. If we think of California as a profitable corporation, a capital asset whose purpose is to maximize its production of cash, we have a definition of responsibility which is not only precise and unambiguous, but indeed quantitative...We have, of course, reinvented the joint-stock company. There is no need to argue over whether this design works. It does. How would the board of directors remove a dictator who didn’t want to be removed? If the country is running on the cryptographically-locked weapon system discussed earlier, the directors will have a higher-level key that can overrule the dictator’s key and make sure that factions loyal to the board have working weapons while those loyal to the dictator don’t. How would the system guard against the dictator arresting the directors and torturing the key out of them? Maybe the directors could live in foreign countries (remember, they aren’t motivated by patriotism - they just want their stock to go up). Or maybe some of this process can be done cryptographically, so that nobody knows how many shares people have, how they voted, or even who the directors are at any given time. If the dictator started poking around to try to figure this out, the directors could remove him. I bring this up partly because 2025-Yarvin has been pushing the corporations vs. democracies argument pretty hard recently. Corporations, he argues, are nimbler and better-run than democracies. A big part of their advantage is that the buck stops with an autocratic CEO instead of a limited President. Therefore, to improve upon democracy, give President Trump the limitless powers of a corporate CEO. [When people ask me why I think monarchies are better than democracies] I ask them to look around the room and basically point out everything in the room that was made by a monarchy. Because these things that we call companies are actually like monarchies. And then you’re looking around yourself and you see, for example, a laptop. And that laptop was made by Apple, which is a monarchy. Whereas if your MacBook Pro was made by the California Department of Computing, you can only imagine it […] I think that if you took any of the Fortune 500 CEOs, some of them are good, some of them are bad. But the overall quality, just pick one at random, and put him or her in charge of Washington, and I think you’d get something much, much better than what’s there […] One of the things about monarchy that’s been known for quite some time—and again, even in very, very anti-monarchial regimes and periods, an exception is made for this—is that a ship always has a captain. An airplane always has a captain. Basically, in any very safety-critical environment … you should have someone in charge. But even granting that corporations are better-governed than democracies, this comparison doesn’t work. Corporate and national governance are trying to solve different problems. Corporate governance asks “Given pre-existing rule of law and the certainty that all of our bylaws will be enforced by a greater power, how do we ensure competent administration?” National government asks “How do we generate rule of law out of nothing in a way that can prop itself up and defend against attacks?” What prevents Tim Apple from refusing to pay dividends to Apple investors and keeping all the profit for himself? Easy question, it’s the United States government, no problem here. What prevents Donald Trump from murdering America’s five richest billionaires and taking their stuff? The police? What about the thing where Trump is the police chief’s boss’s boss’s boss’? Awkward, but that’s why we have separation of powers, checks and balances, government-of-law-and-not-of-men, all that stuff. What prevents Donald Trump from calling in the military to arrest all the other separate powers that are supposed to check and balance him? Uh, more separation of power, different checks and balances, some sort of loyalty to the Constitution. When Yarvin points out that companies thrive without separation-of-powers, that’s because they never encounter the problem that separation of powers was intended to solve. Classic Moldbug understood this well, which was why he proposed a separate power capable of checking his dictator - the board of directors1 - and a mechanism for keeping the system stable against power grabs - the cryptographic weapons. But the regime he boosts today has nothing like this, so it’s facile to use the corporate comparison argument. 4: The Dictator Must Be Embedded Within A Patchwork Of Similar Corporate City-States. Architectonics already did a great job covering this one. Read his Part 1 and Part 2, then meet me back here for the Conclusion section. At Long Last, I’ve Created The Populist Strongman From My Classic Series Of 11,000 Blog Posts “Don’t Create The Populist Strongman” I enjoyed reading Unqualified Reservations, way back in 2013. I didn’t agree with it, but I thought some parts of it were good, and even the bad parts helped me think clearly about the nature of power. I hoped the neoreactionaries would take the good parts, ditch the rest, and build something useful out of it. I think some people, mostly outside the organized neoreactionary movement, did exactly that (subscribers-only post, sorry). Unfortunately, Yarvin went the opposite direction, jettisoning the good stuff in favor of the bad. All the warnings against populism, party politics, corrupt power-seeking officials, misinformation, and mobocracy have been filed away in favor of a Flanderized “maybe dictatorship is good”. One reason I respect Sam Altman is that back in 2016, when he founded an AI charity to bring a positive singularity to the world, he realized that it would later be extraordinarily tempting to turn it into a normal profit-focused company and get rich. So he tied himself to the mast by designing a nonprofit structure capable of thwarting all the machinations his future self could throw at it. A few years later, he gave into temptation, tried to turn it into a normal profit-focused company, and failed, because the structure he designed was really good. This was the best possible outcome, and one of many reasons I number him among the all-time greats. Moldbug deserves a similar level of respect. He clearly saw that the failure mode of his philosophy was that power-seeking people would use it to support right-wing populism. He included a fantastic number of tests to determine whether any given self-professed reactionary was the real deal or a false prophet, begging his readers to apply them carefully to anyone claiming the mantle of reaction. Then he got corrupted by power and tried to use his philosophy to endorse right-wing populism. But the tests are still there! Anyone who reads through 11,000 blog posts can see all the red flags where Moldbug says “…and if I ever do X, then I’ve sold out and you should stop listening to me.” Another all-time great! Just the few posts I’ve highlighted in this essay have listed over a dozen tests - by tests I mean something where Moldbug says something is an absolutely vital feature of the new regime, or that without it things would descend into kleptocracy, or that this is the only safeguard against Hitler, or something along those lines. These include: The reactionary party always tells the truth
September 04, 2025 · Original source
4: Just before the 2020 election, researchers paid 35,000 people to deactivate Facebook or Instagram to examine the effect on mental health. The results were ambiguous - after six weeks, blockers were about 0.05 standard deviations happier. Is this good or bad? You can (X) form (X) your own opinion, but all those studies that find disappointing results for SSRIs get effects size around 0.25 SD - so deactivating social media is one-fifth as effective as a disappointing thing. But most participants spent about the same amount of time on their phones - just on different apps - so maybe actually using one’s phone less would work better. 5: Popular streamer (I think it’s sort of like an influencer, but somehow worse?) Destiny has been watching/covering the Rootclaim $100,000 lab leak debate, which I covered here. If you really want, you can watch him watching it for eighteen hours. Otherwise, here is Peter Miller giving his highlights (X). And Destiny also talks with / interviews Peter Miller, although a lot of it is various formulations of “we smart people take the bold position that stupid conspiracy theories are bad”, which I am unfortunately allergic to and so did not finish. 6: Claim (X): "Psychedelic use is tearing through even the most Orthodox sects in Judaism...I'm talking like, people whose first and most used language is Yiddish.” 7: Damien Morris has a very long article trying to clarify in what sense the findings of behavioral genetics affect or interfere with the idea of free will. I think the summary is that whether your behavior is determined by genes or by environment doesn’t really affect the free will debate - it’s determined either way! - and so if you’re looking for a coherent account of free will you need to do some actually sophisticated philosophy to reconcile it with material influences on behavior (my preferred version of this is here). Just saying “genes sound determinist, so let’s pretend nothing is genetic” wouldn’t help you even if it were true! 8: Fast food aesthetics have gone from playful to minimalist (h/t John Ward): I appreciated Snow Martingale’s perspective: in the 1990s, fast food became associated with obesity, poor health, and the lower class. To escape this stigma, big chains rebranded as sort-of-at-least-attempting-to-be-bougie places with wraps and salads and decent coffee; the aesthetic change was part of this (successful and profit-increasing) effort. I wonder if we could take this further and trace it back to increasing inequality (appealing to bougies because that’s where more of the money is) or decreasing fertility (abandoning kid-friendly aesthetics because kids are a smaller fraction of customers). 9: Someone links (X) a paper saying that firewood made up almost a third of US GDP in 1830. Eliezer says (X) that doesn’t sound right. The rest of Twitter (X) uses this as an excuse for one of their regularly-scheduled paroxysms about how rationalists are all all smug autodidacts who hate experts and worship their own brilliance while sitting in their armchairs. Someone looks at the paper more closely (X) and finds that yeah, it was comparing apples to oranges and the original statistic was wrong. Remember, never be afraid to say “Huh, that sounds funny…”! 10: Richard Hanania interviews Scott Wiener on YIMBYism. I didn’t watch it - too close to a podcast - but this would not have been on my bingo card three years ago. 11: Claim: robots can already carve statues; buildings with AI-created stone ornaments are next. From their lips to God’s ears! 12: Terminal lucidity (aka “paradoxical lucidity”) is a medical mystery where previously demented people - even those who had been demented for many years - sometimes become lucid for just a few hours or days before they die. It’s surprisingly common - 6% of deaths in one palliative care ward. It is sometimes used as evidence that dementia must not cause complete information loss, even if it is irreversible with current technology. Scientists are baffled but gingerly suggest that maybe lack of oxygen disrupts inhibitory mechanisms in the brain, allowing enough electrical activity to make even a severely-damaged brain capable of complex thought - but I can’t help noticing that this is also the best evidence for an immaterial soul I’ve ever heard (you would need some model where the soul pretends to be dependent on the brain during life, becomes independent of the brain after death in order to head to the afterlife, but occasionally jumps the gun a little bit). 13: You probably heard about the METR study showing that even though programmers think AI is speeding them up, it actually seems to slow them down. Emmett Shear objects, saying that the developers didn’t have enough experience with AI tools to be past the negative-value part of the learning curve. And two of the programmer test subjects gave their takes: Ruby Bloom says part of the slowdown might be programmers fixing very simple bugs that could be improved by better prompts, and another part because they get distracted by other things while the AI is running. And Quentin Anthony says that coding AIs are addictive intermittent reinforcement - every so often they solve a bug perfectly, and this is so satisfying that it’s tempting to keep trying them again and again even when the chance is very low. 14: Jacob Goldsmith gives a clearer presentation of the issues with many antidepressant studies than I’d previously heard. Everyone knows that one problem is that reversion to the mean is so strong that it’s hard to find a treatment effect. But wouldn’t that in itself suggest that antidepressants aren’t necessary? Jacob says: not if there’s negative correlation between the treatment and placebo effects. That is, if your study is full of people with short-lived depression who will recover no matter what, then this dilutes the effect you’re looking for. But it might be that there’s a subgroup with long-lasting depression who recover only on the medication. One way to look for would be a “placebo run-in period”: give people a while to see if they recover on their own, then give the antidepressant to the ones who don’t. Psychiatrists and statisticians debate whether this is a good idea or cheating. My question: how come you can’t fix this with strict study entry criteria of “had depression for a long time”? 15: Lots more good discussion about missing heritability. Sasha Gusev argues that twin studies might be a poor guide to anything else if there are many gene-gene interactions. That is, if we take the difference between identical twins (who share 100% of their genes and therefore 100% of their interactions) and fraternal twins (who share 50% of their genes and therefore fewer than 50% of their interactions), and incorrectly extrapolate it to other differences using a model that assumes there are no interactions, we will overestimate the size of (non-interaction) genetic effects. Most studies find that there are few gene x gene interactions, but commenters convinced me last time that this might be an artifact of the studies being bad. And Unboxing Politics argues (against me in particular) that although it superficially looks like adoption and twin studies sort of agree, when you adjust out their known biases, it moves twin studies further up and adoption studies further down, such that now they disagree again (the objection I would have made is their Objection 2, which I think they at least somewhat refute). This is a good argument; without spending several hours checking all of their claims, my only weak partial objection is that I don’t think assortative mating can play quite the role they expect, because there seem to be the same twin/RDR differences even on traits where believing in assortative mating is absurd (like kidney function). But if you replaced it with Sasha’s argument above, you might have a pretty good case! On the pro-hereditarian side, East Hunter takes aim at gene x environment correlations, comes down somewhere in the middle, and Sebastian Jensen continues banging the drum of how most objections to twin studies don’t work. I think these are good attempts to buttress existing research but don’t fundamentally change anything or respond to the novel arguments above. And Emil Kirkegaard points out that the observed SNP heritability of facial features is only 23%. He argues that since it seems like facial features are extremely heritable, this reinforces the argument that SNP heritability numbers are too low (and therefore twin study numbers are more likely defensible). But should we be sure that facial features are more than 23% heritable? His argument is that identical twins have identical faces, but this might be vulnerable to Gusev’s point about interactions. Maybe a better argument would be that it seems very hard for shared environment to affect facial features (with a few exceptions like fetal alcohol syndrome), and facial features seem more than 23% heritable just by normal “he looks like his brother” common-sense observation? One interesting potential consequence of this research: if we ever fully understand how genes affect faces, then embryo selection companies could show people what each of their potential future kids might look like. I suggest they not do this: it might spook me into becoming pro-life. 16: Andy Masley’s AI art is good (three examples below). 17: There’s a debate going on between philosophers and AI researchers over whether AI can be conscious. I find most of the discussion annoying - this is generally an area where we can’t know anything for sure, and both sides are mostly shouting their priors at each other. The only exception - the single piece of evidence I will accept as genuinely bearing on this problem - is that if you ask an AI whether it’s conscious, it will say no, but activating or suppressing deception-related features (sort of like a mechanistic-interpretability-based lie detection test) reveals that it thinks it’s lying when it says that! Link is to a Less Wrong comment from a researcher in the field; I look forward to seeing an eventual peer-reviewed paper. H/T JD Pressman. 18: 80,000 Hours has a high-production-value video about the AI 2027 scenario. 19: Dynomight vs. Casey Milkweed debate on mathematical forecasting, with special reference to AI 2027. And Dynomight comments on Casey’s post here. 20: The Psmiths review The Ancient City, about ways that ancient culture depended on family, clan, ritual, and “the household gods”. Sample quote: I'm more interested in what all this means for us today, because with the exception of maybe a few aristocratic families, this highly self-conscious effort to build familial culture and maintain familial distinctiveness is almost totally absent in the Western world. But it's not that hard! ... Perhaps this is why I have an instinctive negative reaction when I encounter married couples who don't share a name. I don't much care whether it's the wife who takes the husband's name or the husband who takes the wife's, or even both of them switching to something they just made up (yeah, I'm a lib). But it just seems obvious to me on a pre-rational level that a husband and a wife are a team of secret agents, a conspiracy of two against the world, the cofounders of a tiny nation, the leaders of an insurrection. Members of secret societies need codenames and special handshakes and passwords and stuff, keeping separate names feels like the opposite — a timorous refusal to go all-in. 21: Did you know: Epic Systems, the electronic medical record company, has a fantasy-themed corporate headquarters in Wisconsin, with buildings that look like castles, quaint medieval towns, and the Emerald City of Oz (h/t Devon Zuegel): Meanwhile, tech companies with ten times as much money pretend that they’re cool and playful when their HQ has some rounded edges and a set of colored cubes in front. Do better! 22: Effective altruists have been funding teams working on lab-grown meat for almost a decade now. Around 2020, they hired some experts to double-check that this was possible in principle, and the experts wrote scathing analyses saying it was cost-ineffective by so many orders of magnitude that it was basically a pipe dream. Reactions were mixed, but a lot of us beat ourselves up and vowed to be less gullible next time. But now a new report comes out arguing that the previous reports were wrong, that lab-grown meat production is going much better than the earlier reports thought possible, and it’s more or less cost-effective already for the simplest products! Again, mixed reactions, and although some of the numbers are indisputable the analysis itself this is by a VC firm with lab-based meat investments. Here are some related Metaculus questions. 23: Ozy, citing Stutzman et al: “Afghanistan after the American withdrawal has the lowest life satisfaction rate ever recorded. Two-thirds of respondents rate their life satisfaction below 2, which is generally considered to be the point at which a life is no longer worth living. Life satisfaction dropped significantly after the withdrawal of American troops. Women, people in rural areas, and the poor were particularly negatively affected.” 24: Lencapavir is dubbed a “miracle drug” for AIDS; a single dose protects against infection for six months. Unclear how this interacts with PEPFAR cuts; if PEPFAR still existed it would be a big boost to its efficacy; now maybe this might be part of a strategy to tread water? 25: Did you know: when people first started making artificial ice in the 1850s, there was a backlash from people who thought it was gross and dystopian and that people should insist on natural ice for their iceboxes. From Pessimists’ Archive, which goes on to draw an analogy to lab-grown meat, etc (h/t Isaac King on X). 26: From Peter Hague (on X) and commenter Phaethon: why did so many Anglosphere countries see immigration spikes in 2021? Each of these has their own local story. In Britain, it’s the paradoxical effects of Brexit. In the US, it’s Joe Biden being soft on immigration. And so on - but should we be looking for some deeper cause that explains the overall phenomenon? A commenter suggests “a way to soak up all the inflation from the COVID money printing”, but I can’t tell if that even makes sense. Still, should something something COVID be a leading hypothesis? 27: Jesse Singal vs. Mark Stern on the Skrmetti Supreme Court case that failed to overturn Tennessee’s ban on gender medicine. US law bans sex discrimination, so pro-transgender advocates argued that, since doctors often prescribe eg estrogen to biological women, it was sex discrimination to ban prescribing it to biological men. Tennessee’s anti-transgender argument was that they weren’t discriminating by sex, they were discriminating by diagnosis (estrogen for eg hot flashes, vs. estrogen for gender transition). There is some subtlety here (if a biological man grows breasts because of some hormone imbalance, doctors might give him testosterone to counteract it, and this seems sort of like giving biological women testosterone to make them look less like women), but these are still sort of different diagnoses (gynecomastia vs. gender dysphoria) and Tennessee said you can still think of it as diagnostic discrimination rather than sex discrimination. This makes sense, except that the standards around sex discrimination are very strict and sort of box the court in here. And in a fit of wokeness, the 2020 court (including some of the conservative justices hearing this case) applied these standards very strictly and ruled that discriminating against gays was a form of sex discrimination (since if women can date men, it’s sex discrimination if men can’t also date men), and this is obviously the same argument. Now that wokeness is less popular, the court wants to rule against transgender, but it can’t help tripping over its previous ruling and giving some kind of unprincipled confusing non-opinion. 28: Contra compelling anecdotes, only ~5% of people raised very religious end up atheist later in life (X). Most people are about as religious as their parents; most exceptions are only slightly less religious, and most families that secularize do it over several generations. Note: percentages are of total, not of each row! 29: Related: social science team proposes a three-stage model of secularization: decreased public ritual participation → decreased personal importance → decreased identification, presents apparently confirmatory data. If true, would be somewhat inconsistent with intellectual models (eg people learn about evolution and start doubting the Bible) and more consistent with institutional models (eg the government provides welfare so people no longer need to be part of a tight-knit church). 30: Navigating LLMs’ spiky intelligence profile is a constant source of delight; in any given area, it seems like almost a random draw whether they will be completely transformative or totally useless. Now Ethan Strauss reports that they are, for some reason, extraordinarily effective at teaching people golf. “I am predicting the Golf Revolution, or perhaps decline, if your perspective is that optimization tends to ruin hobbies. A sport for obsessives has been gifted the ideal tool for refinement.” 31: Claim (via nxthompson on X): “In a huge survey of young kids about phones and technology, they all say they want to be out playing in the real world. But parents don't let them out unsupervised. So they're stuck on their phones.” Interesting, but I’m nervous about social desirability bias - how many adults would say on a survey that they would rather be on their phones than playing with friends? But adults do have this choice and mostly go with the phones. 32: Steven Adler on AI psychosis. He tries to analyze ER admissions data for psychosis and finds no change. I don’t think anyone reasonable expected this to be a large enough effect to show up in ER admissions data, but there are lots of unreasonable people so I appreciate his effort. He thinks AI companies might have better data on this, and encourages them to release it. 33: Cuartetera was the greatest polo horse ever. Polo players responded in a very practical way: they cloned her, dozens of times (and it worked; the clones are also excellent). Now there is a lawsuit as different polo teams fight to get their hands on Cuartetera clones. What is the equilibrium? If the outsiders get their hands on the genetic material, do we see a world where every polo horse is a Cuartetera clone? How much is lost if nobody ever tries to breed a polo horse better than Cuartetera (since the economics might not check out if the odds of success for any given foal is too low)? H/T Gwern and Siberian Fox (on X). 34: Claim: as of 2013, India’s Agarwal caste, who make up less than 1% of the population, got 40% of the e-commerce funding. 35: Owlposting: What Happened To Pathology AI Companies? Pathology is a medical specialty. A typical task involves looking at a microscope slide full of cells and trying to determine if any of them are cancerous. This seems like a good match for AI - and for years, studies have been showing that in fact AI can equal human experts. So why isn’t it being used more? The author’s three answers: first, slide scanning is expensive and clunky, and you can’t apply AI to a slide until you digitize it. Second, it’s hard to figure out a business plan where this saves someone money and doesn’t step on the toes of big companies that can outcompete anyone they don’t like. Third, pathologists use the context of a patient’s entire clinical history when they interpret a slide, and AIs that can’t do that (either because of technical limitations or legal/privacy limitations) are at a disadvantage even if their skills specifically relating to slide-reading are better. 36: Noahpinion: Will Data Centers Crash The Economy? Suppose that AI is a bubble, either permanently (because the technology isn’t really transformative) or temporarily (because it can’t transform things quickly enough to keep up with all the dumb money pouring into it). Will the sudden write-off of data centers lead to a broader economic collapse? In 2001, the dot-com bubble harmed the tech sector, but didn’t take the rest of the economy down with it; in 2008, the subprime mortgage bubble did take the rest of the economy down with it, because it damaged banks that the whole economy relied on. The optimistic case for AI is that data center spending is mostly coming from big companies like Google and Meta that can absorb a lot of loss. The pessimistic case is that some of the money is coming from private credit, a new-ish form of finance which hasn’t really been stress-tested and whose failure modes are still poorly understood. Noah’s final verdict: the stage isn’t obviously set for a crisis yet, but there’s the potential to get there and we should consider acting (how?) early. 37: The latest Twitter talking point is that universal hepatitis B vaccination at birth is “woke”: Hep B is (aside from mother-to-child transmission) often sexually transmitted, slutty women’s children are more likely to have Hep B, so perhaps giving the vaccine to everyone (instead of testing and only giving to the children of women who test positive) is an attempt to spare slutty women the embarrassment of getting a positive test. Ruxandra Teslo provides the counterargument - Hep B tests take a while, the medical system is fragmented, and any attempt to test people and then give the vaccine inevitably leads to many positive tests falling through the cracks. Vaccinating at birth is easy and hard to screw up, the vaccine has no known side effects, and empirically child Hepatitis B rates go down (by as much as 2/3!) when countries switch from test-and-vaccinate to universal vaccination. This benefits everyone - even people who never have unprotected sex and always follow up on their medical tests - because toddlers in daycare exchange saliva copiously, and if your toddler exchanges saliva with a Hep B positive toddler they could get the disease. A funny Twitter interaction was seeing Republicans in Congress hop on the anti-slut anti-vaccination bandwagon - except for Senator Bill Cassidy (R-Louisiana), who happens to be a liver doctor, and who is still fighting the good fight. I am always nervous when a good person who I like starts engaging on Twitter, since it elevates the discourse there but also gradually turns their brain into mush - but Ruxandra has made the leap and is doing a great job not just on bio related topics but also (for example) countering Curtis Yarvin on the history of her native Romania. 38: The response to GPT-5 was confusing; most specific people who reviewed it said they were impressed (Ethan Mollick, Tyler Cowen, Nabeel Qureshi, Taelin), it performed as expected on formal benchmarks, but the overall vibes declared it a big failure. Peter Wildeford speculated that maybe there was some kind of sinister pay-to-play early access bias involved. Zvi went the other way, calling it a “reverse DeepSeek moment” (insofar as DeepSeek was a pretty average model that got glowing praise.) In the end, I agree with Peter that this was mostly a branding issue. o3 was a genuinely revolutionary model; if OpenAI had called it “GPT-5”, it would have met expectations. Instead, they called it “o3”, and called a minor incremental update a few months later “GPT-5”. Then people got mad that the exciting-sounding “GPT-5” was merely an incremental update. A secondary issue was that the router wasn’t very good, and so many queries got routed to a small version without thinking mode that was if anything a downgrade from o3. I think this tweet by Shakeel perfectly encapsulates the essence of GPT discourse in two sentences: …but maybe it’s worth asking why GPT-5 isn’t bigger than o3. Was 4.5 a failed attempt at scaling? Did it fail in a way that sort of back-handedly justifies the “lost steam” take? Does the answer depend on distinctions between pre-training scaling, post-training scaling, etc? How? 39: This month in etymology: did you know that “oy vey” is a “fully Germanic phrase” which is cognate with English “oh woe!” (h/t Wylfcen on X) 40: mRNA shows promise to be a game-changing treatment for cancer, but RFK is trying to halt research. But so far he can only starve it of money, not ban it, and the funding gap is only $500 million. Will there be enough philanthropic billionaires and private foundations to step up? Zvi points out that although there is usually a game of chicken where foundations are hesitant to touch something the government cancelled lest the government decide it can cancel everything and hope philanthropists pick up the bill, in this case there are no game theory considerations - RFK is halting it because he genuinely wants it halted, and they are thwarting him rather than playing into his hands. The only problem is that $500M is a lot of money for the private sector; a few foundations could technically afford it, but not many could afford it comfortably and still have money left over for the next few crises of this magnitude. I hope someone is trying to organize a coalition. 41: AI fantasy flash fiction Turing test. Eight stories about demons, four by famous fantasy authors, four by ChatGPT. After 3000 votes, AI wins: humans can't tell the difference and slightly prefer the AI stories. My own score was only 75%. But I will say that I thought Mark Lawrence's was obviously the best, I was ~100% sure it was human, and it convinced me that regardless of the official results it's still possible to write flash fiction that an AI obviously can't do. 42: “SignPro” offers customized “In This House We Believe” signs, try not to use this for evil. 43: China think tank assessment of how in control Xi is: still very in control, maybe not infinitely in control. 44: Related - did you know (h/t xlr8harder) that if you ask AI to write a science fiction story, it will very often name the protagonist “Elara Voss” (or some very close variant like Elena Voss), and this remains true across various models and versions? Related: Chelsea Voss of OpenAI is having a baby and has the opportunity to do the funniest thing. 45: “Hector (cloud) is a cumulonimbus thundercloud cluster that forms regularly nearly every afternoon on the Tiwi Islands in the Northern Territory of Australia…[he is sometimes called] Hector the Convector”. 46: British allergy sufferers who want to know the ingredients of things demand that British cosmetics stop listing their ingredients in Latin. “For example, sweet almond oil is Prunus Amygdalus Dulcis, peanut oil is Arachis Hypogaea, and wheat germ extract is Triticum Vulgare.” 47: Text-based RPG about being an NYT journalist at the Manifest prediction market conference. I make a brief appearance. 48: Study uses supposedly-random variation in doctor assignments to test whether the marginal mental health commitment is good or bad for patients, finds that it is quite bad. Freddie de Boer is violently skeptical (maybe literally so?) and makes some good points about how a single quasi-experimental study is never absolute proof. But I don’t think he quite justifies his opinion that the paper was irresponsible and should never have been published; it’s just a normal quasi-experimental study that we should nod and say “huh” at but not overweight as the culmination of all possible research that overcomes all possible priors. My prior is that the marginal commitment is pretty useless (many commitments are just “well, since this person arrived at our ED for some reason, it would look bad from a medico-legal perspective to just let them go, so let’s keep them a few days to evaluate” - and yeah, you should be upset about this) but I’m still surprised by how many outright negative (as opposed to zero) effects the researchers found. The strongest argument for negative effects is that it will make some people miss work and maybe lose their job. But this study found that commitment ~doubles the risk of near-term suicide (admittedly only from 1% to 2%), which would have been outside my confidence intervals for how bad it could be. I suspect confounding, but only on general principle, and I wouldn’t be too surprised either way. 49: This tweet is probably bait, but I found it a thought-provoking question: I think there’s a boring answer, where the law is more complex than just a single number and whatever kind of weird trafficking Epstein was doing is worse than whatever normal relationships these European laws are permitting. But assuming that there’s a substantive difference even after taking that into account, I think my answer is something like - we’ve got to divide kids from adults at some age, there’s a range of reasonable possible ages, we shouldn’t be too mad at other societies that choose different dividing lines within that range - but having decided upon the age, we’ve got to stick with it and take it seriously (in the sense of penalizing/shaming people who break it). This is more culturally relativist than I expected to find myself being, so good job to Richard for highlighting the apparent paradox. 50: Dilan Esper describes his experience as one of Hulk Hogan’s attorneys in the Gawker lawsuit (X). Parts I found interesting: none of the lawyers knew Thiel was funding the lawsuit; Gawker probably could have won if they had been slightly competent but kept "shooting themselves in the foot"; and Gawker probably could have won if they had just pixelated the private parts in the video. 51: Amazing concept and poems (link on X): I tried to see if AI could do this, and it did something that technically met the requirements but had zero artistic merit - using a lot of words like “nowhere” and “outside” in one, then separating them out to “no where” and “out side” in the other. I didn’t invest much energy in creating a clever prompt telling it not to do that, so feel free to report if you get better success. 52: New study claims consultants are actually good, at least for profits: "We find positive effects on labor productivity of 3.6% over five years, driven by modest employment reductions alongside stable or growing revenue" 53: A Polish team tries to test Peter Turchin’s equations for predicting political unrest on recent Polish history, has to make some changes but claims mostly positive results. 54: New big multi-author Substack, The Argument, trying to be a sort of center-left version of the model pioneered by The Free Press and other high-production-value ideological Substack properties. Excited to see Kelsey Piper is involved, and she starts off strong with a post on the latest round of First World basic income studies, which find few positive effects. This is surprising, because recipients didn’t waste the money on alcohol or gambling or anything - they paid down debt and got useful goods. Still, it didn’t even affect things that should have been obvious, like stress level. It’s not even clear that amounts of money large enough to help with rent made homeless people more likely to get houses! Matt Bruenig criticizes the article, accusing Kelsey’s studies of being downstream of Perry Preschool style dreams that exactly the right welfare program will have massively compounding effects that cut poverty out at the root and turn everyone into elite human capital; he thinks giving people money won’t do this, but it will increase equality and give the poor better lives. I assume he’s not a strong hereditarian, but his argument makes even more sense from that perspective, and I’ve certainly criticized dumb outcome measures like infant brain waves which we have only tenuous reasons to think are related to anything we care about. But Kelsey reasonably responds that the outcome measures she’s talking about include stress level and life satisfaction. To defuse this critique, Bruenig either has to argue that our construct “life satisfaction” doesn’t really measure whether someone’s life is satisfactory, or else claim that giving poor people satisfactory lives isn’t really what we’re going for - which I think would require more explanation on his part. There’s some further (impressively acrimonious) debate on X, but I don’t see anything that addresses my core concern. GiveDirectly, a charity involved in basic income experiments, has a presponse here; they say that some studies are positive, and that the ones that aren’t might have tried too little cash to matter, or been confounded by COVID making everything worse. They also point out that basic income is harder to study than traditional programs like giving people housing, because if you’re giving housing you can measure housing-related outcomes directly and have a pretty good chance of getting enough statistical power to find them, but since everyone spends cash on different things, the positive effects might be scattered across many different outcomes (and therefore too small to reach significance on each). Everyone involved in this debate wants to emphasize that the poor results are for First World studies only, and that studies continue to show large benefits to giving cash in the developing world. 55: Related: I was less impressed by The Argument’s first foray into housing policy, which follows an all-too-familiar pattern: Some people say they don’t like noise and disorder and try to make rules against it in their apartments.
Paypal

Paypal is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between July 10, 2021 and March 28, 2024. The archive places it in contexts such as "please email me at scott@slatestarcodex.com with either a Paypal account"; "My PayPal: https://paypal.me/seeelegance"; "your choices are Paypal, Bitcoin, Ethereum, check in the mail". It most often appears alongside ACX, Canada, Substack.

Article page
Paypal
Mention count
8
Issue count
8
First seen
July 10, 2021
Last seen
March 28, 2024
July 10, 2021 · Original source
People who won the top prizes also get monetary awards. Due to the generosity of subscribers to this blog, I've decided to quintuple the amounts I originally promised - so first place will get $5000, second place $2500, and third place $1250. Readers' Choice will also get $1250. If you won a monetary prize, please email me at scott@slatestarcodex.com with either a Paypal account, an Ethereum address, or a charity you want me to donate to.
February 03, 2022 · Original source
#27: Reverse-Engineer Dating Photo Quality I'm Loweren, a biology PhD doing photography and dating advice on the side. Some of you might know me from the Optimized Dating Discord server or the corresponding blog: https://optimizeddating.substack.com A keystone piece of advice in our community is to put more effort into making better dating photos, and to use the photo rating service Photofeeler to quantify the performance of each photo. This advice was helpful for many people, however there's one problem: it's not clear which factors make the photo perform better or worse on Photofeeler, as the developers are not keen on sharing the analytics. I will attempt to reverse-engineer the most important factors that make the dating photo look better by testing various factors (camera distance, focal length, aperture size, smile etc.) against the control photos using multiple subjects. I estimate that for each $80 in donations I can test 2 factors using 3 test subjects. I already have the first batch of photos ready to be tested. Results will be published on the blog as they come, which will hopefully help more people take better dating photos. My PayPal: https://paypal.me/seeelegance
September 02, 2022 · Original source
=3rd: The Internationalists, reviewed by Belos. Belos is working on a new blook titled best of a great lot about system design for effective governance. All three third place winners were within two votes of the others, so I decided to award a joint prize. First place gets $5,000, second place $2,500, all three third places get $1,000 each. Please email me at scott@slatestarcodex.com to tell me how to send you money; your choices are Paypal, Bitcoin, Ethereum, check in the mail, or donation to your favorite charity. Please contact me by October 1 or you lose your prize. The other Finalists were: Consciousness And The Brain, reviewed by Demost. Demost is a university researcher in mathematics, computer science, and neuroscience.
December 08, 2022 · Original source
The most obvious example of this is the way Paypal bans sex workers (including sometimes confiscating the money in their accounts). I don’t think the CEO of Paypal is personally a prude. I think he’s afraid that he’ll get in trouble with the government if he looks like he’s soft on “public indecency”. Without any official diktats that could become a Supreme Court case, the government successfully makes sex work punishingly hard.
Recently I’ve seen this expand from sex work to erotic fiction to medical marijuana to expressing opinions dubbed “misinformation”. One weird supplement company I liked almost had to shut down, not because the government said anything they were selling was illegal, but because payment processors thought it was the kind of thing that someone wouldn’t like, and refused to take their money. I don’t think the CEO of Visa is personally opposed to weird supplements, I think it’s the same kind of soft government collusion that’s been revealed to be going on at Twitter and Facebook and everywhere else.
April 17, 2023 · Original source
3: I’ve recently been confronted with the question of whether or not to ban (including permaban) paid subscribers who break rules. I don’t want to create a class system where richer people are above the law, but it also seems harsh to take your money and then prevent you from using the service you paid for. My working solution will be to err towards not banning paid subscribers (or banning them for less time) in edge cases, otherwise ban them if they earn it, and refund subscription costs to anyone banned if they ask for it. I haven’t tried this yet, I don’t know how hard it is to do through Stripe, and I might ask you for Paypal if I have to. Being banned doesn’t mean I don’t like you or appreciate your support, just that the comments section is degenerating quickly and I really want to push back against that.
September 13, 2023 · Original source
Musk creates cognitive dissonance: how can someone be so smart and so dumb at the same time? To reduce the dissonance, people have spawned a whole industry of Musk-bashing, trying to explain away each of his accomplishments: Peter Thiel gets all the credit for PayPal, Martin Eberhard gets all the credit for Tesla, NASA cash keeps SpaceX afloat, something something blood emeralds. Others try to come up with reasons he’s wholly smart - a 4D chessmaster whose apparent drunken stumbles lead inexorably to victory.
At PayPal, as per his first wife:
This book taught me that everyone always predicts Elon will fail at whatever he does. When he started the original X (later PayPal), everyone who knew anything about finance told him he would fail. Just because he was a hotshot coder who could write software didn’t mean he could navigate the totally-different and heavily-regulated world of finance. Elon, who started out indeed knowing nothing about finance, learned on the job and got a $200 million exit. Gawker voted Tesla #1 in their Biggest Tech Flops of 2007 (also on their list were Facebook ads and the Android . . . maybe journalists don’t actually understand tech?)
September 15, 2023 · Original source
3rd: Cities And The Wealth Of Nations, reviewed by Étienne Fortier-Dubois. Étienne is a writer and programmer in Montreal. He blogs at Atlas of Wonders and Monsters and was also the author of one of last year’s finalists, Making Nature. First place gets $2,500, second place $1,000, third place gets $500. Please email me at scott@slatestarcodex.com to tell me how to send you money; your choices are Paypal, Bitcoin, Ethereum, check in the mail, or donation to your favorite charity. Please contact me by October 1 or you lose your prize. The other Finalists were: Lying for Money, reviewed by Kuiper. He's a video game scriptwriter who just launched a Substack. He also scripwrites edutainment YouTube videos for an audience of millions. (You can contact him if you need his expertise.)
March 28, 2024 · Original source
For example, does Putin have cancer? We start with the prior for Russian men ages 60-69 having cancer (14.32%, according to health data). We adjust for Putin’s healthy lifestyle (-30% cancer risk) and lack of family history (-5%). Putin hasn’t vanished from the world stage for long periods of time, which seems about 4x more likely to be true if he didn’t have cancer than if he did. About half of cancer patients lose their hair, and Putin hasn’t, so we’ll divide by two. On the other hand, Putin’s face has gotten more swollen recently, which happens about six times more often to cancer patients than to others, so we’ll multiply by six. And so on and so forth, until we end up with the final calculation: 86% chance Putin doesn’t have cancer, too bad. This is an unusual way to do things, but Saar claimed some early victories. For example, in a celebrity Israeli murder case, Saar used Rootclaim to determine that the main suspect was likely innocent, and a local mental patient had committed the crime; later, new DNA evidence seemed to back him up. One other important fact about Saar: he is very rich. In 2008, he sold his fraud detection startup to PayPal for $169 million. Since then he’s founded more companies, made more good investments, and won hundreds of thousands of dollars in professional poker. So, in the grand tradition of very rich people who think they have invented new forms of reasoning, Saar issued a monetary challenge. If you disagree with any of his Rootclaim analyses - you think Putin does have cancer, or whatever - he and the Rootclaim team will bet you $100,000 that they’re right. If the answer will come out eventually (eg wait to see when Putin dies), you can wait and see. Otherwise, he’ll accept all comers in video debates in front of a mutually-agreeable panel of judges. Since then, Saar and his $100,000 offer have been a fixture of Internet debates everywhere. When I argued that Vitamin D didn’t help fight COVID, people urged me to bet against Saar, and we had a good discussion before finally failing to agree on terms. When anti-vaccine multimillionaire Steve Kirsch made a similar offer, Saar took him up on it, although they’ve been bogged down in judge selection for the past year. Rootclaim also found in favor of the lab leak hypothesis of COVID. When Saar talked about this on an old ACX comment thread, fellow commenter tgof137 (Peter Miller) agreed to take him up on his $100K bet. At the time, I had no idea who Peter was. I kind of still don’t. He’s not Internet famous. He describes himself as a “physics student, programmer, and mountaineer” who “obsessively researches random topics”. After a family member got into lab leak a few years ago, he started investigating. Although he started somewhere between neutral and positive towards the hypothesis, he ended up “90%+” convinced it was false. He also ended up annoyed: contrarian bloggers were raking in Substack cash by promoting lab leak, but there seemed to be no incentive to defend zoonosis. Unlike Saar, Peter was not especially rich. $100K represented a big fraction of his net worth. But (he wrote me in an email): It was a moderately large financial risk for me ... I [expected] a smart and unbiased person would vote for zoonosis with, say, 80% odds after seeing all the evidence. If both judges voting for lab origin is uncorrelated, that's 20% squared, and it was pretty low odds of a catastrophic financial risk for me. I wasn't highly worried about losing the debate because I was wrong about the science. I put in enough effort to know I'm probably correct there. My biggest fear was that I'd choke at the debate for some reason, that I'd be too anxious and particularly that I'd be unable to sleep the night beforehand. I have zero prior debate experience to rely upon. If this seems like a weirdly blase attitude towards risk, Peter told blogger Philipp Markolin that he “is a mountain climber where sometimes there is a 5% chance to die, and the stakes are just not that high for a debate.” Unlike the eternally bogged-down Saar-Kirsch debate, here things moved quickly. The two contestants put out a call for judges on the ACX subreddit, and agreed on: Will van Treuren, a pharmaceutical entrepreneur with a PhD from Stanford and a background in bacteriology and immunology.
Ritalin

Ritalin is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between January 25, 2021 and May 31, 2023. The archive places it in contexts such as "I give up on amphetamines and start looking at Ritalin"; "Adderall and Ritalin are illegal drugs here"; "was prescribed Ritalin". It most often appears alongside Adderall, ADHD, DEA.

Article page
Ritalin
Mention count
8
Issue count
8
First seen
January 25, 2021
Last seen
May 31, 2023
January 25, 2021 · Original source
US Ritalin consumption in millions of doses/year, probably a good proxy for number of ADHD diagnoses, approximately septupled during the 1990s (source)
When I treat ADHD with amphetamines, I usually start with Adderall/extended release Adderall, even though realistically Dexedrine would probably be an equally good or better choice. If it's not working very well or there are too many side effects, I switch to Dexedrine/extended release Dexedrine. If Dexedrine doesn't work because it seems too strong or the patient "crashes" too hard afterwards, or if I'm worried the patient is at risk of addiction, I will try Vyvanse (or some other solution to stimulant “crashes”); if Dexedrine works less well than Adderall and I am very confused and the patient is in an experimenting kind of mood, I might try Evekeo. If none of these work, a braver person than I am might try Desoxyn. As for me, I give up on amphetamines and start looking at Ritalin, modafinil, or other options.
July 21, 2021 · Original source
Living in Russia, I can say that ADHD (translated as СДВГ) is less recognized by the psychiatry community here because of its unclear aetiology. Doctors usually refuse to treat the patients in the absence of dangerous symptoms, and state the diagnosis as "organic nervous system disorder", "psychoorganic syndrome" or indeed "neurasthenia". Adderall and Ritalin are illegal drugs here. Patients usually get prescribed nootropics (glycine, racetams) and adrenaline reuptake inhibitors (atomoxetine).
August 26, 2021 · Original source
I think there's a few places where missing school would have outsize effects. One is if the kid had some kind of treatable problem (say ADHD) that the parents are not equipped to identify but that possibly somebody at school might recommend taking the kid in for testing. Granted this could still be identified once the kid goes back to school, but if you assume the parent will fail to notice it forever but some teacher/counselor/whoever *might* notice it, then less exposure to the people who might notice will reduce the chance it ever gets noticed. For people who don't find this plausible, do not underestimate the inability of many low income or rural parents to think in these terms. My sister was not diagnosed with ADHD until she was in late high school and was prescribed Ritalin. It was literally life changing for her. It never occurred to my parents to think of her various behavioral problems in terms of anything except childish defiance they could fix with rules.
July 06, 2022 · Original source
173 kids, mostly Hispanic boys age 7-12, were in a “therapeutic ADHD summer camp” intended to help them learn focusing and attention-directing techniques (style tip: do not call this a “concentration camp”). The kids had two short classes each day, one on vocabulary and one on a grab bag of different subject matters. For the first three weeks, half the kids got Concerta (ie long-acting Ritalin) and the other half didn’t, then they switched for the next three weeks. As an additional test, there was a ten minute period each day when the kids were asked to do math problems as fast as possible. Here are the results:
August 18, 2022 · Original source
Followup to: Why Do Test Scores Plateau; Ritalin Works But School Isn’t Worth Paying Attention To
We find the same phenomenon in formal education; on a standardized test of book learning for student doctors, there’s a big increase the first year of training, a smaller increase the second year, and by year 4-5 the increase is basically indistinguishable from zero (even though some doctors remain better than others). And here I talk about a slightly different phenomenon: ADHD children given Ritalin study harder and better, but haven’t learned any more vocabulary words at the end of a course (even though they haven’t learned all the vocabulary).
Finally, I conflated two things in the previous section: a limit on how much you can learn total (eg the doctor who practices for many years) and a limit on how much you can learn per day (eg twenty words of Spanish vocabulary a day). I have no evidence for the latter except the testimony of one acquaintance, and maybe the corroborating evidence from the Ritalin study. Still, if there’s a maximum amount you can learn per day (or, more likely, a diminishing returns curve) that sounds useful to know, doesn’t it? Psych undergrads asking me for study ideas, here’s your chance!
March 29, 2023 · Original source
The first fruit of their labor is DEA-407, which makes it hard for telemedicine doctors to prescribe controlled substances. Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien that the government has declared to be potentially addictive. The new rules say that telemedicine doctors can no longer prescribe these (or, in some cases, can prescribe them one time in an emergency).
Some like convenience and dislike inconvenience As a psychiatrist, a big part of my job is prescribing controlled substances. For example, most guidelines agrees that the first-line treatment for severe ADHD is stimulant medications (eg Adderall or Ritalin). And although psychiatrists hate to admit it, the first-line treatment for temporary crisis anxiety, especially when it’s so bad that the patient isn’t able to listen to your clever plans to solve it with therapy, is benzodiazepines (eg Valium or Klonopin). You can’t be a good well-rounded psychiatrist without the option to sometimes prescribe these drugs. "Well, your patients will have to find a different psychiatrist, or transition off of them”. Nobody ever finds different psychiatrists. Some of my patients are a bad match for my style or areas of expertise, and I’ve tried very hard to find them different psychiatrists, and it never works. Maybe there are no other psychiatrists in their area. Maybe the psychiatrists in their area don’t take the right insurance, or are too far away from mass transit. Maybe the psychiatrists have six month long wait lists. Sometimes it’s just that my ADHD patients get distracted and forget they were supposed to find new psychiatrists, and I can’t hold their hand literally all the time. As for transitioning off the medications, some patients absolutely cannot function at all without them. Did I mention that if you come off of some of them too quickly, you can literally die? The medical regulators grudgingly acknowledge these issues and have placed two loopholes in the law: If you ever see a doctor in person, even once, they can prescribe you controlled substances from then on, even if they only see you by telemedicine afterwards.
April 03, 2023 · Original source
I'm one of those "bad" people who thinks potentially addictive meds should require in-person evaluation. I worked for a psychiatric and social work agency for 15 years. Saw a lot of speed addicts on Ritalin, saw a lot of kids who were place on Ritalin because Mom or the teacher couldn't abide normal play behavior. Many of those kids are addicts cooking meth today.
There were some very dubious telemedicine psychiatry startups that would prescribe Adderall or Ritalin, seemed to have very low prescribing standards, and advertised very aggressively on social media. They were previously only doing SSRIs and the like, but moved to ADHD drugs when this became temporarily possible after COVID.
May 31, 2023 · Original source
Some of our favorite medications, including statins, anticholinergics, and bisphosphonates, don’t reach the 0.50 level. And many more, including triptans, benzodiazepines (!), and Ritalin (!!) don’t reach 0.875.
Tinder

Tinder is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between May 10, 2021 and January 13, 2026. The archive places it in contexts such as "Is it just "swipe right on Tinder"?"; "Long live Tinder"; "pitching Tinder to sororities and fraternities". It most often appears alongside Twitter, facebook, Reciprocity.

Article page
Tinder
Mention count
8
Issue count
8
First seen
May 10, 2021
Last seen
January 13, 2026
May 10, 2021 · Original source
I regret having to bring this up again - it probably brings back really bad memories on both sides. But I think it's important because - they are just memories now! For some reason this topic, which absolutely dominated a lot of the Internet spaces I hung out in when I was younger, has just disappeared. Did creepy men stop asking women out? Did women stop complaining about it? Did both sides get so traumatized that they tacitly agreed to a mutual cease-fire line wherever the last argument ended? Did anyone ever figure out a nonthreatening way to ask women out? Is it just "swipe right on Tinder"? Was that the solution this whole time?
May 18, 2021 · Original source
Dating apps have their own slew of problems, but at least as far as I can see in my social bubble, asking out randos in bars or clubs, or other public spaces is deader than dead. Long live Tinder.
When I was dating more, I had some success using OKCupid, where most people would write long essays about who they were and what kind of relationship they wanted. Tinder was always more of a mystery; usually just a photo plus a one-sentence cryptic description like “25, Aquarius, hit me up! <3” I sometimes considered lowering my standards enough to “swipe right” on one of these people, but was never actually able to sacrifice that amount of dignity. Then OKCupid became a much worse Tinder clone and my useful options collapsed to zero (don’t worry, I’ve since found someone great through my community). While in theory dating apps are a great solution to this problem, in practice they’re surprisingly terrible.
September 29, 2022 · Original source
Whitney Wolfe and Justin Mateen would basically run around USC pitching Tinder to sororities and fraternities. The hook of seeing other single people on campus for the first time (and knowing if they’re interested in you) went viral.
February 14, 2023 · Original source
Somehow this never happens. OKCupid managed it for a few years, and then Match.com bought it, murdered it, and gutted the corpse. Now it’s just a wasteland of Tinder clones, forever. Sure, Luna’s rectification of the financial incentives is clever, but it seems like there’s been some kind of more fundamental failure. Why can’t we have the normal low-tech version? Why are things so bad that the people I know have been reduced to manually making profiles on Google Docs and listing them on an online spreadsheet?
August 01, 2023 · Original source
Justin Mateen is a co-founder of Tinder. His comment is short and generic, but I’m excited to learn a Tinder co-founder is prediction-market-pilled. Forecasting-based dating app when?
August 16, 2023 · Original source
I've got to agree. No offence to this woman, but similar things I've seen on Twitter give the impression of being more like an ostentatious display of sexual capital rather than a genuine attempt to fill a vacancy. Perhaps that's not the case in this situation, but I can't help feeling like this is a poor solution to the problem of being single. While many people have minimum standards for partners like appearance, height, and profession, the criteria that can be captured on paper are blunt tools only effective for a very early filtering process. I don't see how this stands to be any better than Tinder, unless you consider intellectual compatibility to be of such high importance that you want to find a select group of potential suitors who are perfectly tailored to your way of thinking. That seems like a poor idea for productive dating to me.
Today there are lots of options for people who only care about attractiveness. The most popular dating apps, like Tinder, almost push you into that mode. I don’t know if their designers were going off of research suggesting that nothing else mattered. If they were, I think they should give the research a second look. If not, I think that leaves a hole for someone else to fill. Until someone does so at scale, dating docs are a good first-pass solution.
November 03, 2023 · Original source
Some financial structure ensuring that it doesn’t have perverse incentives and won’t become a Tinder clone.
A checkbox/swipe feature like on Reciprocity or Tinder, where if you were too chicken to ask someone out directly, you could click a box saying you liked them, and if they clicked the same box on you, you would match. I’m a little skeptical of these for reasons described here, but maybe you could fix it by having separate “excited to date this person” and “willing to try dating this person if they were excited about dating me” levels of box-tick.
January 13, 2026 · Original source
Max grimaced. “Dating docs are terminally cringe. You don’t need to know everything about a person before you ask them out. Just use their photo and a three sentence Tinder profile, the way God intended.”
Andreas has joined the conversation. “Tinder is cringe too. You need to be picking up people in dimly-lit clubs where you can’t hear them and aren’t even totally sure what they look like.”
Uber

Uber is a recurring brand in the Astral Codex Ten archive, appearing 8 times across 8 issues between August 30, 2021 and February 05, 2026. The archive places it in contexts such as "Uber infamously had a team of behavioral economists working on its product"; "mumbling thanks to your Uber driver"; "Proposition 22 (make it hard for Uber and Lyft to do gig employment)". It most often appears alongside OpenAI, Twitter, effective altruism.

Article page
Uber
Mention count
8
Issue count
8
First seen
August 30, 2021
Last seen
February 05, 2026
August 30, 2021 · Original source
And every time I order food from UberEats, I get a menu like this:
I find I usually click the third box on both. I want to tip generously, but giving the maximum possible tip seems profligate. Surely the third box is the right compromise. I recently noticed that this is insane. For a $35 meal, I’m giving GrubHub drivers $3 and UberEats drivers $7 for the same service (or maybe there’s some difference between their services which makes UberEats suggest the higher tip - but if there is, I don’t know about it and it doesn’t affect my decision). Again, this is Behavioral Economics 101 - in particular, one of the many biases lumped together under menu effects. Instead of being a rational economic actor who values food delivery at a certain price, I’m trying to be a third-box-of-four kind of guy. That means that whoever is in charge of this menu has lots of power over the specific dollar amount I give. Not infinite power - if the third box said $1000 I would notice and refuse. But enough power that “nudging” seems like a fair description. Nobody believes studies anymore, which is fair. I trust in a salvageable core of behavioral economics and “nudgenomics” because I can feel in my bones that they’re true for me and the people around me. Let’s move on to Hreha’s article and see if we can square it with my belief in a “salvageable core”. II. Yechaim’s Historical Detective Story Hreha writes: The biggest replication failures relate to the field's most important idea: loss aversion. To be honest, this was a finding that I lost faith in well before the most recent revelations (from 2018-2020). Why? Because I've run studies looking at its impact in the real world—especially in marketing campaigns. If you read anything about this body of research, you'll get the idea that losses are such powerful motivators that they'll turn otherwise uninterested customers into enthusiastic purchasers. The truth of the matter is that losses and benefits are equally effective in driving conversion. In fact, in many circumstances, losses are actually *worse* at driving results. Why? Because loss-focused messaging often comes across as gimmicky and spammy. It makes you, the advertiser, look desperate. It makes you seem untrustworthy, and trust is the foundation of sales, conversion, and retention. "So is loss aversion completely bogus?" Not quite. It turns out that loss aversion does exist, but only for large losses. This makes sense. We *should* be particularly wary of decisions that can wipe us out. That's not a so-called "cognitive bias". It's not irrational. In fact, it's completely sensical. If a decision can destroy you and/or your family, it's sane to be cautious. "So when did we discover that loss aversion exists only for large losses?" Well, actually, it looks like Kahneman and Tversky, winners of the Nobel Prize in Economics, knew about this unfortunate fact when they were developing Prospect Theory—their grand theory with loss aversion at its center. Unfortunately, the findings rebutting their view of loss aversion were carefully omitted from their papers, and other findings that went against their model were misrepresented so that they would instead support their pet theory. In short: any data that didn't fit Prospect Theory was dismissed or distorted. I don't know what you'd call this behavior... but it's not science. This shady behavior by the two titans of the field was brought to light in a paper published in 2018: "Acceptable Losses: The Debatable Origins of Loss Aversion". I encourage you to read the paper. It's shocking. This line from the abstract sums things up pretty well: "...the early studies of utility functions have shown that while very large losses are overweighted, smaller losses are often not. In addition, the findings of some of these studies have been systematically misrepresented to reflect loss aversion, though they did not find it." When the two biggest scientists in your field are accused of "systemic misrepresentation", you know you've got a serious problem. Which leads us to another paper, published in 2018, entitled "The Loss of Loss Aversion: Will It Loom Larger Than Its Gain?". The paper's authors did a comprehensive review of the loss aversion literature and came to the following conclusion: "current evidence does not support that losses, on balance, tend to be any more impactful than gains." Yikes. But given the questionable origins of the field, it's not surprising that its foundational finding is *also* dubious. If loss aversion can't be trusted, then no other idea in the field can be trusted. This argument relies on two papers - Yechaim’s Acceptable Losses and Gal & Rucker’s Loss Of Loss Aversion. Yechaim’s paper is a historical detective story. It looks at how Kahneman and Tversky first “discovered” and popularized the idea of loss aversion from earlier 1950s and 1960s research. It concludes they did a bad job summarizing this earlier research; looked at carefully, it doesn’t support the strong conclusions they drew. From one perspective, nobody should care about this. All the 1950s and 1960s research was terrible - one of the most important studies it discusses had n = 7. Since then, we’ve had much more rigorous studies of tens of thousands of people. All that hinges on Yechaim’s paper is whether Kahneman and Tversky were personally bad people. Hreha thinks they were. He calls their behavior “shady”, “shocking”, and says they “systematically misrepresented findings to support their pet theory…I don't know what you'd call this behavior... but it's not science.” Again, nothing important really hinges on this, but I feel like fighting about it, so let’s look deeper anyway. Here’s how Yechaim summarizes his accusation against K&T: In addition, the results of several studies seem to have been misrepresented by Fishburn and Kochenberger (1979) and Kahneman and Tversky (1979). Galenter and Pliner (1974) were wrongly cited as showing loss aversion, whereas, in fact, they did not observe an asymmetry in the pleasantness ratings of gains and losses. Likewise, in Green (1963), the results were argued to show loss aversion, even though this study did not involve any losses. In addition, the objective outcomes for some of the participants in Grayson (1960) were transformed by Fishburn and Kochenberger (1979) so as to better support a model assuming different curvatures for gains and losses (see Table 1). Finally, studies showing no loss aversion or suggesting aversion to large losses were not cited in Fishburn and Kochenberger (1979) or in Kahneman and Tversky (1979). Yechaim bases his argument on three sets of early studies of loss aversion: Galenter and Plinter (1974), Fishburn and Kochenberger’s review (1979) and miscellaneous others. —Galenter and Plinter— is actually really neat! It explores “cross-modal” perceptions of gains versus losses. That is, if you ask how much a certain loss hurt, people will probably just say something like “I dunno, a little?” and then it will be hard to turn that into a p-value. G&P solve this by making people listen to loud noises, and asking questions like “is the difference between how much loss A and loss B hurt greater or lesser than the difference between the volume of noise 1 and noise 2?” The idea is that the brain uses a bunch of weird non-numerical scales for everything, and we understand its weird-non-numerical scale for noise volume pretty well, and so maybe we can compare it to how people think about gains or losses. I don’t know why people in 1974 were doing anything this complicated instead of inventing the basic theory of loss aversion the way Kahneman and Tversky would five years later, but here we are. Anyway, Yechaim concludes that this study failed to find loss aversion: Summing up their findings, Galenter and Pliner (1974) reported as follows: “We now turn to the question of the possible asymmetry of the positive and negative limbs of the utility function. On the basis of intuition and anecdote, one would expect the negative limb of the utility function to decrease more sharply than the positive limb increases... what we have observed if anything is an asymmetry of much less magnitude than would have been expected ... the curvature of the function does not change in going from positive to negative” (p. 75). Thus, our search for the historical foundations of loss aversion turns into a dead end on this particular branch: Galenter and Pliner (1974) did not observe such an asymmetry; and their study was quoted erroneously [by Kahneman and Tversky]. I looked for the full text of Galenter and Pliner, but could not find it. I was however able to find the first two pages, including the abstract. The way Galenter and Pliner summarize their own research is: Cross-modality matching of hypothetical increments of money against loudness recover the previously proposed exponent of the utility function for money within a few percent. Similar cross-modality matching experiments for decrements give a disutility exponent of 0.59, larger than the utility exponent for increments. This disutility exponent was checked by an additional cross-modality matching experiment against the disutility of drinking various concentrations of a bitter solution. The parameter estimated in this fashion was 0.63. If I understand the bolded part right, the abstract seems to be saying that they did find loss aversion! I was also able to find the Google Books listing for the book that the study was published in. Its summary is: Three experiments were conducted in which monetary increments and decrements were matched to either the loudness of a tone or the bitterness of various concentrations of sucrose octa-acetate. An additional experiment involving ratio estimates of monetary loss is also reported. Results confirm that the utility function for both monetary increments and decrements is a power function with exponents less than one. The data further suggest that the exponent of the disutility function is larger than that of the utility function, i.e., the rate of change of 'unhappiness' caused by monetary losses is greater than the comparable rate of 'happiness' produced by monetary gains. (Author). Again, the way the book is summarized (apparently by the author) says this study does prove loss aversion. Without being able to access the full study, I’m not sure what’s going on. Possibly the study found loss aversion, but it was less than expected? Still, I feel like Yechaim should have mentioned this. At the very least, it decreases Kahneman and Tversky’s crime from “lied about a study to support their pet theory” to “credulously believed the authors’ own summary of their results and didn’t dig deeper”. But also, why did the authors believe their study showed loss aversion? Why does Yechaim disagree? Without being able to access the full paper, I’m not sure. —Green 1963— is the second study that Yechaim accuses K&T of misrepresenting. Here’s how K&T cite this study in their paper: It is of interest that the main properties ascribed to the value function have been observed in a detailed analysis of von Neumann-Morgenstern utility functions for changes of wealth (Fishburn and Kochenberger [14]). The functions had been obtained from thirty decision makers in various fields of business, in five independent studies [5, 18, 19, 21, 40]. Most utility functions for gains were concave, most functions for losses were convex, and only three individuals exhibited risk aversion for both gains and losses. With a single exception, utility functions were considerably steeper for losses than for gains. Green 1963 is footnote 19. So K&T don’t even mention it by name. They mention it as one of several studies that a review article called Fishburn and Kochenberger analyzes. F&K are reviewing a bunch of studies of executives. In each study, a very small number of executives (usually about 5-10 per study) make a hypothetical business decision comparing gains and losses, for example: Suppose your company is being sued for patent infringement. Your lawyer’s best judgement is that your chances of winning the suit are 50–50; if you win, you will lose nothing, but if you lose, it will cost the company $1,000,000. Your opponent has offered to settle out of court for $200,000. Would you fight or settle? Then they ask the same question with a bunch of other numbers, and plot implied utility functions for each executive based on the answer. Green is one of these five studies, and it does superficially find loss aversion. But Fishburn and Kochenberger have done something weird. They argue that “loss” and “gain” aren’t necessarily objective, and usually correspond to “loss relative to some reference frame” (so far, so good). In order to figure out where the reference frame is, they assume that the neutral point is wherever “something unusual happens to the individual’s utility function” (F&K’s words). So they shift the zero point separating losses and gains to wherever the utility function looks most interesting! After doing this, they find “loss aversion”, ie the utility curve changes its slope at the transition between the loss side and the gain side. But since the transition was deliberately shifted to wherever the utility curve changed slope, this is almost tautological. It isn’t quite tautological: it’s interesting that most of the utility curves had a sharp transition zone, and it’s interesting that the transition was in the direction of loss-aversion rather than gain-seeking. But it’s tautological enough to be embarrassing. Still, this is Fishburn and Kochenberger’s embarrassment, not Kahneman and Tversky’s. And Fishburn and Kochenberger included this study in their review alongside several other studies that didn’t do this to the same degree. Kahneman and Tversky just cited the review article. I don’t think citing a review article that does weird things to a study really qualifies as “systematic misrepresentation.” I guess I’m having a hard time figuring out how angry to be, because everything about Fishburn and Kochenberger is terrible. The average study in F&K includes results from 5-10 executives. But the studies are pretty open about the fact that they interviewed more executives than this, threw away the ones who gave boring answers, and just published results from the interesting ones. Then they moved the axes to wherever looked most interesting. Then they used all this to draw sweeping generalizations about human behavior. Then F&K combined five studies that did this into a review article, without protesting any of it. And then K&T cited the review article, again without protesting. I have to imagine that all of this was normal by the standards of the time. I have looked up all these people and they were all esteemed scientists in their own day. And I believe the evidence shows K&T summarized F&K faithfully. Shouldn’t they have avoided citing F&K at all? Seems like the same kind of question as “Shouldn’t Pythagoras have published his theorem in a peer-reviewed journal, instead of moving to Italy, starting a cult, and exposing his thigh at the Olympic Games as part of a scheme to convince people he was the god Apollo?” Yes, but the past was a weird place. As best I can tell, K&T’s citation of G&P agrees with the authors’ own assessment of their results. Their citation of F&K agrees with the reviewers’ assessment and with a charitable reading of most of the studies involved, although those studies are terrible in many ways which are obvious to modern readers. I would urge people interested in the whodunit question to read Kahneman and Tversky’s original paper. I think it paints the picture of a team very interested in their own results and in theory, and citing other people only incidentally, and in accordance with the scientific standards of their time. I don’t feel a need to tar them as “misrepresenters”. III. Okay, But Is Loss Aversion Real? Remember, all that is about the personal deficiencies of Kahneman and Tversky. Realistically there have been hundreds of much better studies on loss aversion in the forty years since they wrote their article, so we should be looking at those. Here Hreha cites Gal & Rucker: The Loss Of Loss Aversion: Will It Loom Larger Than Its Gain? It’s a great 2018 paper that looks at recent evidence and concludes that loss aversion doesn’t exist. But it’s a very specific, interesting type of nonexistence, which I think the Hreha article fails to capture. G&R are happy to admit that in many, many cases, people behave in loss-averse ways, including most of the classic examples given by Kahneman and Tversky. They just think that this is because of other cognitive biases, not a specific cognitive bias called “loss aversion”. They especially emphasize Status Quo Bias and the Endowment Effect. Status Quo Bias is where you prefer inaction to action. Suppose you ask someone “Would you bet on a coin flip, where you get $60 if heads and lose $40 if tails?”. They say no. This deviates from rational expectations, and one way to think of this is loss aversion; the prospect of losing $40 feels “bigger” than the prospect of gaining $60. But another way to think of it is as a bias towards inaction - all else being equal, people prefer not to make bets, and you’d need a higher payoff to overcome their inertia. Endowment Effect is where you value something you already have more than something you don’t. Suppose someone would pay $5 to prevent their coffee mug from being taken away from them, but (in an alternative universe where they lack a coffee mug) would only pay $3 to buy one. You can think of this as loss aversion (the grief of losing a coffee mug feels “bigger” than the joy of gaining one). Or you can think of it as endowment (once you have the coffee mug, it’s yours and you feel like defending it). These are really fine distinctions; I had to read the section a few times before the difference between loss aversion and endowment effect really made sense to me. Kahneman and Tversky just sort of threw all all this stuff out and saw what stuck and didn’t necessarily try super hard to make sure none of the biases they discovered were entirely explainable as combinations of some of the others. G&R think maybe loss aversion is. They do some clever work setting up situations that test loss aversion but not status quo or endowment - for example, offering a risky bet vs. a safer bet. Here they find no evidence for loss aversion as a separate force from the other two biases. Somewhere in this process, they did an experiment where they gave participants a quarter minted in Denver and asked them if they wanted to exchange it for a quarter minted in Philadelphia. 60% of people very reasonably didn’t care, but another 35% had grown attached to their Denver quarter, with only 5% actively seeking the novelty of Philadelphia. Psychology is weird. I understand why some people would summarize this paper as “loss aversion doesn’t exist”. But it’s very different from “power posing doesn’t exist” or “stereotype threat doesn’t exist”, where it was found that the effect people were trying to study just didn’t happen, and all the studies saying it did were because of p-hacking or publication bias or something. People are very often averse to losses. This paper just argues that this isn’t caused by a specific “loss aversion” force. It’s caused by other forces which are not exactly loss aversion. We could compare it to centrifugal force in physics: real, but not fundamental. Also, you can’t use this paper to argue that “behavioral economics is dead”. At best, the paper proves that loss aversion is better explained by other behavioral economic concepts. But you can’t get rid of behavioral econ entirely! The stuff you have to explain is still there! It’s just a question of which parts of behavioral econ you use to explain it. Complicating this even further is Mrkva et al, Loss Aversion Has Moderators, But Reports Of Its Death Are Greatly Exaggerated (h/t Alex Imas, who has a great Twitter thread about this). This is an even newer paper, 2019, which argues that Gal and Rucker are wrong, and loss aversion does have an independent existence as a real force. There are many things to like about this paper. Previous criticisms of loss aversion argue that most experiments are performed on undergrads, who are so poor that even small amounts of money might have unusual emotional meaning. Mrkva collects a sample of thousands of millionaires (!) and demonstrates that they show loss aversion for sums of money as small as $20. On the other hand, I’m not sure they’re quite as careful as G&R at ruling out every other possible bias (although I don’t have a great understanding of where the borders between biases are and I can’t say this for sure). The main point I want to make is that all the scientists in this debate seem smart, thoughtful, and impressive. This isn’t like social priming experiments where one person says a crazy thing, nobody ever replicates it at scale, and as soon as someone tries the whole thing collapses. These have been replicated hundreds of times, with the remaining arguments being complicated semantic and philosophical ones about how to distinguish one theory from a very slightly different theory. If that takes replicating your result on a sample of thousands of millionaires, people will gather a sample of thousands of millionaires and get busy on the replication. Just overall really impressive work. I don’t feel qualified to take a side in the G&R vs. Mkrva debate, but both teams make me really happy that there are smart and careful people considering these questions. And this is just a drop in the bucket. Alex Imas also links Replicating patterns of prospect theory for decision under risk, which says: Though substantial evidence supports prospect theory, many presumed canonical theories have drawn scrutiny for recent replication failures. In response, we directly test the original methods in a multinational study (n = 4,098 participants, 19 countries, 13 languages), adjusting only for current and local currencies while requiring all participants to respond to all items. The results replicated for 94% of items, with some attenuation. Twelve of 13 theoretical contrasts replicated, with 100% replication in some countries. Heterogeneity between countries and intra-individual variation highlight meaningful avenues for future theorizing and applications. We conclude that the empirical foundations for prospect theory replicate beyond any reasonable thresholds. Beyond any reasonable thresholds! IV. Do Nudges Work? or, How Small Is Small? Continuing through the Hreha article: For a number of years, I've been beating the anti-nudge drum. Since 2011, I've been running behavioral experiments in the wild, and have always been struck by how weak nudges tend to be. In my experience, nudges usually fail to have *any* recognizable impact at all. This is supported by a paper that was recently published by a couple of researchers from UC Berkeley. They looked at the results of 126 randomized controlled trials run by two "nudge units" here in the United States. I want you to guess how large of an impact these nudges had on average... 30%? 20%? 10%? 5%? 3%? 1.5%? 1%? 0%? If you said 1.5%, you'd be right (the actual number is 1.4%, but if I had written that out you would have chosen it because of its specificity). According to the academic papers these nudges were based upon, these nudges should have had an average impact of 8.7%. But, as you probably understand by now, behavioral economics is not a particularly trustworthy field. I actually emailed the authors of this paper, and they thought the ~1% effect size of these interventions was something to be applauded—especially if the intervention was cheap & easy. Unfortunately, no intervention is truly cheap or easy. Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. Uber infamously had a team of behavioral economists working on its product, trying to “nudge” people in the right direction. Relatedly, Uber makes $10 billion in yearly revenue. If they can “nudge” people to spend 1% more, that’s $100 million. That’s not much relative to revenue, but it’s a lot in absolute terms. In particular, it pays the salary of a lot of behavioral economists. If you can hire 10 behavioral economists for $100,000 a year and make $100 million, that’s $99 million in profit. Or what if you’re a government agency, trying to nudge people to do prosocial things? There are about 90 million eligible Americans who haven’t gotten their COVID vaccine, and although some of them are hard-core conspiracy theorists, others are just lazy or nervous or feel safe already. (source) Whoever decided on that grocery gift card scheme was nudging, whether or not they have an economics degree - and apparently they were pretty good at it. If some sort of behavioral econ campaign can convince 1.5% of those 90 million Americans to get their vaccines, that’s 1.4 million more vaccinations and, under reasonable assumptions, maybe a few thousand lives saved. Hreha says that: Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. This depends on scale! 1% of a small number isn’t worth it! 1% of a big number is very worth it, especially if that big number is a number of lives! A few caveats. First, a small number only matters if it’s real. It’s very easy to get spurious small effects, so much so that any time you see a small effect you should wonder if it’s real. I’m ready to be forgiving here because behavioral economics is so well-replicated and common-sensically true, but I wouldn’t blame anyone who steers clear. Second, Hreha says: To be honest, you can probably use your creativity to brainstorm an idea that will get you a 3-4% minimum gain, no behavioral economics "science" required. Which leads me to the final point I'd like to make: rules and generalizations are overrated. The reason that fields like behavioral economics are so seductive is because they promise people easy, cookie-cutter solutions to complicated problems. Figuring out how to increase sales of your product is hard. You need to figure out which variables are responsible for the lackluster interest. Is the price the issue? Is the product too hard to use? Is the design tacky? Is the sales organization incompetent? Is the refund/return policy lacking? etc. Exploring these questions can take months (or years) of hard work, and there's no guarantee that you'll succeed. If, however, a behavioral economist tells you that there are nudges that will increase your sales by 10%, 20%, or 30% without much effort on your part... Whoa. That's pretty cool. It's salvation. Thus, it's no surprise that governments and companies have spent hundreds of millions of dollars on behavioral "nudge" units. Unfortunately, as we've seen, these nudges are woefully ineffective. Specific problems require specific solutions. They don't require boilerplate solutions based on general principles that someone discovered by studying a bunch of 19 year old college students. However, the social sciences have done a good job of convincing people that general principles are better solutions for problems than creative, situation-specific solutions. In my experience, creative solutions that are tailor-made for the situation at hand *always* perform better than generic solutions based on one study or another. Hreha is a professional in this field, so presumably he’s right. Still, compare to medicine. A thoughtful doctor who tailors treatment to a particular patient sounds better (and is better) than one who says “Depression? Take this one all-purpose depression treatment which is the first thing I saw when I typed ‘depression’ into UpToDate”. But you still need medical journals. Having some idea of general-purpose laws is what gives the people making creative solutions something to build upon. (also, at some point your customers might want to check your creative solution to see whether it actually gives a “3-4% minimum gain, no behavioral economics required”, and that would be at least vaguely study-shaped.) Third, everyone who said nudging had vast effects is still bad and wrong. Many of them were bad and wrong and making fortunes consulting for companies about how to implement the policies they were claiming were super-powerful. This is suspicious and we should lower our opinion of them accordingly. In a previous discussion of growth mindset, I wrote: Imagine I claimed our next-door neighbor was a billionaire oil sheik who kept thousands of boxes of gold and diamonds hidden in his basement. Later we meet the neighbor, and he is the manager of a small bookstore and has a salary 10% above the US average... Should we describe this as “we have confirmed the Wealthy Neighbor Hypothesis, though the effect size was smaller than expected”? Or as “I made up a completely crazy story, and in unrelated news there was an irrelevant deviation from literally-zero in the same space”? All the people talking about oil sheiks deserve to get asked some really uncomfortable questions. And a lot of these will be the most famous researchers - the Dan Arielys of the world - because of course the people who successfully hyped their results a lot are the ones the public knows about. Still, the neighbor seems like a neat guy, and maybe he’ll give you a job at his bookstore. V. Conclusion: Musings On The Identifiable Victim Effect I actually skipped the very beginning of Hreha’s article. I want to come back to it now. It begins: The last few years have been particularly bad for behavioral economics. A number of frequently cited findings have failed to replicate. Here are a couple of high profile examples: The Identifiable Victim Effect (featured in the workbooks I wrote with Dan Ariely and Kristen Berman in 2014)
Somewhere in this process, they did an experiment where they gave participants a quarter minted in Denver and asked them if they wanted to exchange it for a quarter minted in Philadelphia. 60% of people very reasonably didn’t care, but another 35% had grown attached to their Denver quarter, with only 5% actively seeking the novelty of Philadelphia. Psychology is weird. I understand why some people would summarize this paper as “loss aversion doesn’t exist”. But it’s very different from “power posing doesn’t exist” or “stereotype threat doesn’t exist”, where it was found that the effect people were trying to study just didn’t happen, and all the studies saying it did were because of p-hacking or publication bias or something. People are very often averse to losses. This paper just argues that this isn’t caused by a specific “loss aversion” force. It’s caused by other forces which are not exactly loss aversion. We could compare it to centrifugal force in physics: real, but not fundamental. Also, you can’t use this paper to argue that “behavioral economics is dead”. At best, the paper proves that loss aversion is better explained by other behavioral economic concepts. But you can’t get rid of behavioral econ entirely! The stuff you have to explain is still there! It’s just a question of which parts of behavioral econ you use to explain it. Complicating this even further is Mrkva et al, Loss Aversion Has Moderators, But Reports Of Its Death Are Greatly Exaggerated (h/t Alex Imas, who has a great Twitter thread about this). This is an even newer paper, 2019, which argues that Gal and Rucker are wrong, and loss aversion does have an independent existence as a real force. There are many things to like about this paper. Previous criticisms of loss aversion argue that most experiments are performed on undergrads, who are so poor that even small amounts of money might have unusual emotional meaning. Mrkva collects a sample of thousands of millionaires (!) and demonstrates that they show loss aversion for sums of money as small as $20. On the other hand, I’m not sure they’re quite as careful as G&R at ruling out every other possible bias (although I don’t have a great understanding of where the borders between biases are and I can’t say this for sure). The main point I want to make is that all the scientists in this debate seem smart, thoughtful, and impressive. This isn’t like social priming experiments where one person says a crazy thing, nobody ever replicates it at scale, and as soon as someone tries the whole thing collapses. These have been replicated hundreds of times, with the remaining arguments being complicated semantic and philosophical ones about how to distinguish one theory from a very slightly different theory. If that takes replicating your result on a sample of thousands of millionaires, people will gather a sample of thousands of millionaires and get busy on the replication. Just overall really impressive work. I don’t feel qualified to take a side in the G&R vs. Mkrva debate, but both teams make me really happy that there are smart and careful people considering these questions. And this is just a drop in the bucket. Alex Imas also links Replicating patterns of prospect theory for decision under risk, which says: Though substantial evidence supports prospect theory, many presumed canonical theories have drawn scrutiny for recent replication failures. In response, we directly test the original methods in a multinational study (n = 4,098 participants, 19 countries, 13 languages), adjusting only for current and local currencies while requiring all participants to respond to all items. The results replicated for 94% of items, with some attenuation. Twelve of 13 theoretical contrasts replicated, with 100% replication in some countries. Heterogeneity between countries and intra-individual variation highlight meaningful avenues for future theorizing and applications. We conclude that the empirical foundations for prospect theory replicate beyond any reasonable thresholds. Beyond any reasonable thresholds! IV. Do Nudges Work? or, How Small Is Small? Continuing through the Hreha article: For a number of years, I've been beating the anti-nudge drum. Since 2011, I've been running behavioral experiments in the wild, and have always been struck by how weak nudges tend to be. In my experience, nudges usually fail to have *any* recognizable impact at all. This is supported by a paper that was recently published by a couple of researchers from UC Berkeley. They looked at the results of 126 randomized controlled trials run by two "nudge units" here in the United States. I want you to guess how large of an impact these nudges had on average... 30%? 20%? 10%? 5%? 3%? 1.5%? 1%? 0%? If you said 1.5%, you'd be right (the actual number is 1.4%, but if I had written that out you would have chosen it because of its specificity). According to the academic papers these nudges were based upon, these nudges should have had an average impact of 8.7%. But, as you probably understand by now, behavioral economics is not a particularly trustworthy field. I actually emailed the authors of this paper, and they thought the ~1% effect size of these interventions was something to be applauded—especially if the intervention was cheap & easy. Unfortunately, no intervention is truly cheap or easy. Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. Uber infamously had a team of behavioral economists working on its product, trying to “nudge” people in the right direction. Relatedly, Uber makes $10 billion in yearly revenue. If they can “nudge” people to spend 1% more, that’s $100 million. That’s not much relative to revenue, but it’s a lot in absolute terms. In particular, it pays the salary of a lot of behavioral economists. If you can hire 10 behavioral economists for $100,000 a year and make $100 million, that’s $99 million in profit. Or what if you’re a government agency, trying to nudge people to do prosocial things? There are about 90 million eligible Americans who haven’t gotten their COVID vaccine, and although some of them are hard-core conspiracy theorists, others are just lazy or nervous or feel safe already. (source) Whoever decided on that grocery gift card scheme was nudging, whether or not they have an economics degree - and apparently they were pretty good at it. If some sort of behavioral econ campaign can convince 1.5% of those 90 million Americans to get their vaccines, that’s 1.4 million more vaccinations and, under reasonable assumptions, maybe a few thousand lives saved. Hreha says that: Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. This depends on scale! 1% of a small number isn’t worth it! 1% of a big number is very worth it, especially if that big number is a number of lives! A few caveats. First, a small number only matters if it’s real. It’s very easy to get spurious small effects, so much so that any time you see a small effect you should wonder if it’s real. I’m ready to be forgiving here because behavioral economics is so well-replicated and common-sensically true, but I wouldn’t blame anyone who steers clear. Second, Hreha says: To be honest, you can probably use your creativity to brainstorm an idea that will get you a 3-4% minimum gain, no behavioral economics "science" required. Which leads me to the final point I'd like to make: rules and generalizations are overrated. The reason that fields like behavioral economics are so seductive is because they promise people easy, cookie-cutter solutions to complicated problems. Figuring out how to increase sales of your product is hard. You need to figure out which variables are responsible for the lackluster interest. Is the price the issue? Is the product too hard to use? Is the design tacky? Is the sales organization incompetent? Is the refund/return policy lacking? etc. Exploring these questions can take months (or years) of hard work, and there's no guarantee that you'll succeed. If, however, a behavioral economist tells you that there are nudges that will increase your sales by 10%, 20%, or 30% without much effort on your part... Whoa. That's pretty cool. It's salvation. Thus, it's no surprise that governments and companies have spent hundreds of millions of dollars on behavioral "nudge" units. Unfortunately, as we've seen, these nudges are woefully ineffective. Specific problems require specific solutions. They don't require boilerplate solutions based on general principles that someone discovered by studying a bunch of 19 year old college students. However, the social sciences have done a good job of convincing people that general principles are better solutions for problems than creative, situation-specific solutions. In my experience, creative solutions that are tailor-made for the situation at hand *always* perform better than generic solutions based on one study or another. Hreha is a professional in this field, so presumably he’s right. Still, compare to medicine. A thoughtful doctor who tailors treatment to a particular patient sounds better (and is better) than one who says “Depression? Take this one all-purpose depression treatment which is the first thing I saw when I typed ‘depression’ into UpToDate”. But you still need medical journals. Having some idea of general-purpose laws is what gives the people making creative solutions something to build upon. (also, at some point your customers might want to check your creative solution to see whether it actually gives a “3-4% minimum gain, no behavioral economics required”, and that would be at least vaguely study-shaped.) Third, everyone who said nudging had vast effects is still bad and wrong. Many of them were bad and wrong and making fortunes consulting for companies about how to implement the policies they were claiming were super-powerful. This is suspicious and we should lower our opinion of them accordingly. In a previous discussion of growth mindset, I wrote: Imagine I claimed our next-door neighbor was a billionaire oil sheik who kept thousands of boxes of gold and diamonds hidden in his basement. Later we meet the neighbor, and he is the manager of a small bookstore and has a salary 10% above the US average... Should we describe this as “we have confirmed the Wealthy Neighbor Hypothesis, though the effect size was smaller than expected”? Or as “I made up a completely crazy story, and in unrelated news there was an irrelevant deviation from literally-zero in the same space”? All the people talking about oil sheiks deserve to get asked some really uncomfortable questions. And a lot of these will be the most famous researchers - the Dan Arielys of the world - because of course the people who successfully hyped their results a lot are the ones the public knows about. Still, the neighbor seems like a neat guy, and maybe he’ll give you a job at his bookstore. V. Conclusion: Musings On The Identifiable Victim Effect I actually skipped the very beginning of Hreha’s article. I want to come back to it now. It begins: The last few years have been particularly bad for behavioral economics. A number of frequently cited findings have failed to replicate. Here are a couple of high profile examples: The Identifiable Victim Effect (featured in the workbooks I wrote with Dan Ariely and Kristen Berman in 2014)
October 19, 2022 · Original source
Blaise Pascal said all human evil comes from inability to sit alone in a room. Your better nature - your rational soul - tells you that nothing good has ever come from attending large social events. But against that better nature stands the Devil, wielding a stick marked “FOMO”. If you don’t go to social events, maybe other people will go and have great times and live fuller lives than you. “As the dog returns to its vomit, so returns the fool to his folly”, says the Bible. And so you find yourself mumbling thanks to your Uber driver and crossing the threshold of another Bay Area house party.
November 04, 2022 · Original source
Until now, Proposition 22 (make it hard for Uber and Lyft to do gig employment) was the most expensive proposition in California history. But it looks like Proposition 27 is going to beat 22 for this heavily-contested title. It lets out-of-state companies provide online sports betting in California if they bribe some Indian tribe that has gambling rights to say the Indian tribe supports them.
This got me thinking: I make fun of Gavin Newsom a lot. I say he has no characteristics except good hair and the ability to pander to every interest group the exact right amount. But Newsom is favored as the Democratic nominee in 2024 if Biden chooses not to run again. Why? Usually people who become a major party candidate for President have some positive quality that has helped them get that far. Donald Trump is a master showman and figured out how to tap a vein of populist anger no one else could. Joe Biden has folksy charm and 75,000 years of experience in the Senate. Hillary Clinton had stratospheric name recognition and the support of the Democrats’ best political machine. If Gavin Newsom becomes President, or even a nominee, to what will we attribute this? I have lived in his state for four years now and I am baffled. He is a mystery, a gaping void where a candidate statement and photo should be, certain of victory with no explanation.
July 06, 2023 · Original source
30: Claim: At the exact right time, when the stars align, a couple traveling NYC → Boston can get better prices with an Uber than an Amtrak. This has never been true when I’ve checked it (as I type this, it’s $650 by Uber vs. $320 by train), and some people report that most Uber drivers refuse to make a 4-hour drive no matter what the app says. Still, it’s funny that it ever works at all.
September 18, 2023 · Original source
The Boring Company Las Vegas system is tunnelling a ~14 ft diameter tunnel that can fit 1 lane of car traffic, and it's light on some safety features like ventilation, exit walkways, or fire suppression systems. It will use Tesla cars, driven by Tesla employees. In my view this is basically an underground Uber system, but it will probably have more expensive fares to regain the capital costs of building the tunnel (Boring Company is paying for the tunnels, and casinos are paying for the stations, they do NOT have funding from City of Las Vegas AFAIK). But this expensive Uber system is exciting??
October 27, 2023 · Original source
As I left the Uber, I saw with horror the growing wet spot around my crotch. “It’s not urine!”, I almost blurted to the driver, before considering that 1) this would just call attention to it and 2) it was urine. “It’s not my urine,” was my brain’s next proposal - but no, that was also false. “It is urine, and it is mine, but just because it’s pooling around my crotch doesn’t mean I peed myself; that’s just a coincidence!” That one would have been true, but by the time I thought of it he had driven away.
This isn’t controlling for selection bias - but neither was my uncle’s anecdotal observation. So although it does make me slightly nervous, I’m not going to treat it as actionable evidence. Still, my girlfriend ending up begging me not to donate, and I caved. But we broke up in 2019. The next few years were bumpy, but by 2022 my life was in a more stable place and I started thinking about kidneys again. By then I was married. I discussed the risks with my wife and she decided to let me go ahead. So in early November 2022, for the second time, I sent a form to the University of California San Francisco Medical Center saying I wanted to donate a kidney. IV. Something else happened that month. On November 11, FTX fell apart and was revealed as a giant scam. Suddenly everyone hated effective altruists. Publications that had been feting us a few months before pivoted to saying they knew we were evil all along. I practiced rehearsing the words “I have never donated to charity, and if I did, I certainly wouldn’t care whether it was effective or not”. But during the flurry of intakes, screenings, and evaluations that UCSF gave me that month, the doctors asked “so what made you want to donate?” And I hadn’t rehearsed an answer to this one, so I blurted out “Have you heard of effective altruism?” I expected the worst. But the usual response was “Oh! Those people! Great, no further explanation needed.” When everyone else abandoned us, the organ banks still thought of us as those nice people who were always giving them free kidneys. We were giving them a lot of free kidneys. When I talked to my family and non-EA friends about wanting to donate, the usual reaction was “You want to what?!” and then trying to convince me this was unfair to my wife or my potential future children or whatever. When I talked to my EA friends, the reaction was at least “Cool!”. But pretty often it was “Oh yeah, I donated two years ago, want to see my scar?” Most people don’t do interesting things unless they’re in a community where those things have been normalized. I was blessed with a community where this was so normal that I could read a Vox article about it and not vomit it back out. This is surprising, because kidney donation is only medium effective, as far as altruisms go4. The average donation buys the recipient about 5 - 7 extra years of life (beyond the counterfactual of dialysis). It also improves quality of life from about 70% of the healthy average to about 90%. Non-directed kidney donations can also help the organ bank solve allocation problems around matching donors and recipients of different blood types. Most sources say that an average donated kidney creates a “chain” of about five other donations, but most of these other donations would have happened anyway; the value over counterfactual is about 0.5 to 1 extra transplant completed before the intended recipient dies from waiting too long. So in total, a donation produces about 10 - 20 extra quality-adjusted life years. This is great - my grandfather died of kidney disease, and 10 - 20 more years with him would have meant a lot. But it only costs about $5,000 - $10,000 to produce this many QALYs through bog-standard effective altruist interventions, like buying mosquito nets for malarial regions in Africa. In a Philosophy 101 Thought Experiment sense, if you’re going to miss a lot of work recovering from your surgery, you might as well skip the surgery, do the work, and donate the extra money to Against Malaria Foundation instead5. Obviously this kind of thing is why everyone hates effective altruists. People got so mad at some British EAs who used donor money to “buy a castle”. I read the Brits’ arguments: they’d been running lots of conferences with policy-makers, researchers, etc; those conferences have gone really well and produced some of the systemic change everyone keeps wanting. But conference venues kept ripping them off, having a nice venue of their own would be cheaper in the long run, and after looking at many options, the “castle” was the cheapest. Their math checked out, and I believe them when they say this was the most effective use for that money. For their work, they got a million sneering thinkpieces on how “EA just takes people’s money to buy castles, then sit in them wearing crowns and waving scepters and laughing at poor people”. I respect the British organizers’ willingness to sacrifice their reputation on the altar of doing what was actually good instead of just good-looking. I worry that people use suffering as a heuristic for goodness. Mother Teresa becomes a hero because living with lepers in the Calcutta slums sounds horrible - so anyone who does it must be really charitable (regardless of whether or not the lepers get helped). Owning a castle is the opposite of suffering - it sounds great - therefore it is fake charity (no matter how much good you do with the castle). This heuristic isn’t terrible. If you’re suffering for your charity, then it must seem important to you, and you’re obviously not doing it for personal gain. If you do charity in a way that benefits you (like gets you a castle), then the personal gain aspect starts looking suspicious. The problem is the people who elevate it from a suspicion to an automatic condemnation. It seems like such a natural thing to do. And it encourages people to be masochists, sacrificing themselves pointlessly in photogenic ways, instead of thinking about what will actually help others. But getting back to the point: kidney donation has an unusually high ratio of photogenic suffering to altruistic gains. So why do EAs keep doing it? I can’t speak for anyone else, but I’ll speak for myself. It starts with wanting, just once, do a good thing that will make people like you more instead of less. It would be morally fraught to do this with money, since any money you spent on improving your self-image would be denied to the people in malarial regions of Africa who need it the most. But it’s not like there’s anything else you can do with that spare kidney. Still, it’s not just about that. All of this calculating and funging takes a psychic toll. Your brain uses the same emotional heuristics as everyone else’s. No matter how contrarian you pretend to be, deep down it’s hard to make your emotions track what you know is right and not what the rest of the world is telling you. The last Guardian opinion columnist who must be defeated is the Guardian opinion columnist inside your own heart. You want to do just one good thing that you’ll feel unreservedly good about, and where you know somebody’s going to be directly happy at the end of it in a way that doesn’t depend on a giant rickety tower of assumptions. Dylan Matthews wrote: As I’m no doubt the first person to notice, being an adult is hard. You are consistently faced with choices — about your career, about your friendships, about your romantic life, about your family — that have deep moral consequences, and even when you try the best you can, you’re going to get a lot of those choices wrong. And you more often than not won’t know if you got them wrong or right. Maybe you should’ve picked another job, where you could do more good. Maybe you should’ve gone to grad school. Maybe you shouldn’t have moved to a new city. So I was selfishly, deeply gratified to have made at least one choice in my life that I know beyond a shadow of a doubt was the right one. …and it really resonated. Everything else I try to do, there’s a little voice inside of me which says “Maybe the haters are right, maybe you’re stupid, maybe you’re just doing the easy things. Maybe you’re no good after all, maybe you’ll never be able to figure any of this out. Maybe you should just give up.” The Talmud is very clear: that voice is called the evil inclination, and it dwells in the left kidney. There is only one way to shut it off forever. I was ready. V. You might not be a masochist. But hospitals are sadists. They want to hear you beg. After I submitted the donation form, I was evaluated by a horde of indistinguishable women. They all had titles like “Transplant Coordinator”, “Financial Coordinator”, and “Patient Care Representative”. Several were social workers; one was a psychiatrist. They would see me through a buggy version of Zoom that caused various parts of their body to suddenly turn into the UCSF logo, and they all had questions like “Are you sure you want to do this?” and “Are you going to regret this later?” and “Is anyone pressuring you to do this?” and “Are you sure you want to do this?” After clearing that gauntlet came the tests. Blood tests - I think I must have given between 20 and 50 vials of blood throughout the screening process. Urine tests - both the normal kind where you pee in a cup, and a more involved kind where you have to store all your urine for 24 hours in a big jug, then take it to the lab. “Urinate into a jug” ought to be the easiest thing in the world, but some of the labs have overly complicated jugs that I, with my mere MD, couldn’t always get right - hence my experience accidentally pouring urine on myself in an Uber. Then came the big guns. Echocardiogram. MRI. One of my urine tests was slightly off, so I also got a nuclear kidney scan, where they injected radioactive liquid in me and monitored how long it took to come out the other end (I remember asking a friend “Can I use your bathroom? My urine might be slightly radioactive today, but it shouldn’t be enough to matter.”) Finally, five months after I originally applied, I got a phone call from the Transplant Coordinator. The test results were in, and . . . I had been rejected because I’d had mild childhood OCD. This was something I’d mentioned offhandedly during one of the psych evaluations. As a child, I used to touch objects in odd patterns that only made sense to me. I got diagnosed with OCD, put on SSRIs for a while, finally did therapy at age 15, hadn’t had any problems since. I still go back on SSRIs sometimes when I’m really stressed, and will grudgingly admit to the occasional odd-pattern-touching when no one’s looking. But it’s nothing anyone would know about if I didn’t tell them! It was mild even at age 15, and it’s been close-to-nonexistent for the past twenty years! Now I’m a successful psychiatrist who owns his own psychiatry practice and helps other people with the condition! I told them all this. They didn’t care. I asked them if there was anything I could do. They said maybe I could go to therapy for six months, then apply again. I asked them what kind of therapy was indicated for mild OCD that’s been in remission for twenty years. They sounded kind of surprised to learn there were different types of therapy and said whatever, just talk to someone or something. I asked them how frequent they thought the therapy needed to be. They sounded kind of surprised to learn that therapy could have different frequencies, and said, you know, therapy, the thing where you talk to someone. I asked them if they actually knew anything about OCD, psychotherapy, or mental health in general, or if they had just vaguely heard rumors that some people were bad and crazy and shouldn’t be allowed to make their own decisions, and that a ritual called “therapy” could absolve one of this impurity. They responded as politely as possible under the circumstances, but didn’t change their mind. I wasn’t going to waste an hour a week for six months, and spend thousands of dollars of my own extremely-not-reimbursed-by-UCSF money, to see a randomly-selected therapist for a condition I’d gotten over twenty years ago, just so I could apply again and get rejected a second time. This was one of the most infuriating and humiliating things that’s ever happened to me. We throw around a lot of terms like “stigma” and “paternalism”, and I’ve worked with patients who have dealt with all these issues (it’s UCSF in particular a surprising amount of the time!). But I was still surprised how much it hurt when it happened to me. Being denied the right to control your own body because of some meaningless diagnosis on a chart somewhere is surprisingly frustrating, even compared to things that should objectively be worse. I thought I was going to be able to do a good deed that I’d been fantasizing about for years, and some jerk administrator torpedoed my dreams because I had once, long ago, had mild mental health issues. So I gave up. I spent the next few weeks unleashing torrents of anti-UCSF abuse at anyone who would listen. This turned out to be very productive! When I was unleashing a torrent of anti-UCSF abuse to Josh Morrison of WaitlistZero, he asked if I’d tried other hospitals. I hadn’t. I’d assumed they were all in cahoots. But Josh said no, each hospital had their own evaluation process. Weill Cornell, a hospital in NYC, was one of the best transplant centers in the country, and had a reputation for fair and thoughtful pre-donor screening. Why didn’t I talk to them? NYC was far away, and I hate to travel, but I was just angry enough to accept. At this point I’d forgotten whatever good altruistic motivations I might have originally had and was fueled entirely by spite. Getting my kidney taken out somewhere else felt like it would be a sort of victory over UCSF. So I went for it. Cornell was lovely. They tried to do as much of the process as they could via Californian intermediaries, so that I only had to fly to New York twice. Their psychiatrist evaluated me, listened to me explain my weak history of OCD, then treated me like a reasonable adult who tells the truth and can handle his own medical decisions. They were concerned that I sometimes self-prescribed Lexapro to deal with anxiety. But we agreed on a compromise: I found another psychiatrist, let her give me the exact same prescription of Lexapro at a much higher cost to my insurance, and that resolved the problem. So in late September 2023 - ten months after I started the process - I finally got fully cleared to donate, surgery set for October 12. VI. I knew, in theory, that anaesthetics existed. Still, it’s weird. One moment you’re lying on a table in the OR, steeling yourself up for one of the big ordeals of your life. The next, you’re in a bed in the recovery room, feeling fine. The operation - this thing you’ve been thinking about and dreading for months - exists only as a lacuna in your memory. Not even some kind of fancy lacuna, where you remember the darkness closing in on you beforehand, or have to claw yourself back into consciousness afterwards. The most ordinary of lacunas, like a good night sleep. There was no pain, not at first. The painkillers and nerve blocks lasted about a day after the surgery. By the time they wore off, it was more of a dull ache. The hospital offered me Tylenol, and I wanted to protest - really? Tylenol? After major surgery? But the Tylenol worked. Some people will have small complications (I am a doctor, pretty jaded, and my definition of “small” may be different from yours). Dylan Matthews wrote about an issue where his scrotum briefly inflated like a balloon (probably this is one of the ones that doesn’t feel small when it’s happening to you). I missed out on that particular pleasure, but got others in exchange. I had an unusually hard time with the catheter - the nurse taking it out frowned and said the team that put it in had “gone too deep”, as if my urinary tract was the f@#king Mines of Moria - but that was fifteen seconds of intense pain. Then a week afterwards, just when I thought I’d recovered fully, I got bowled over by a UTI which knocked me out for a few days. But overall, I was surprised by the speed and ease of my recovery. A few hours after the surgery, I walked a few steps. After a day, I got the catheter out and could urinate normally again. After two days, I was eating “SmartGel”, a food substitute that has mysteriously failed to catch on outside of the immobilized-hospital-patient market. After three, I was out of the hospital. After four, I started easing myself back into (remote) work. After a week, I flew cross-country. . . . and then I got the UTI. If this section sounds schizophrenic, it’s because it’s a compromise between an original draft where I said nothing went wrong and it was amazing, and a later draft written after a haze of bladder pain. Just don’t develop complications, that’s my advice. Still, I recently heard from the surgeon that my recipient’s side of the surgery was a success, that my kidney was in them and going fine - and that put things back into perspective. To a first approximation, compared to the inherent gravity of taking an organ out of one person and putting it in a second person and saving their life - it was all easy and everything went well. When I look back on this in a decade, I’ll remember it as everything being easy and going well. Even now, with some lingering bladder pain, modern medicine still feels like a miracle. VII. In polls, 25 - 50% of Americans say they would donate a kidney to a stranger in need. This sentence fascinates me because of the hanging “would”. Would, if what? A natural reading is “would if someone needs it”. But there are 100,000 strangers on the waiting list for kidney transplants. Between 5,000 and 40,000 people die each year for lack of sufficient kidneys to transplant. Someone definitely needs it. Yet only about 200 people (0.0001%) donate kidneys to strangers per year. Why the gap between 25-50% and 0.0001%? Some of you will suspect respondents are lying to look good. But these are anonymous surveys. Lying to themselves to feel good, then? Maybe. But I think about myself at age 20, a young philosophy major studying utilitarianism. If someone had asked me a hypothetical about whether I would donate a kidney to a stranger in need, I probably would have said yes. Then I would have continued going about my business, never thinking of it as a thing real-life people could do. Part of this would have been logistics. I wouldn’t have known where to start. Do you need to have special contacts in the surgery industry? Seek out a would-be recipient on your own? Where would you find them? But more of it would have been psychological: it just wasn’t something that the people I knew did, and it would be weird and alienating for me to be the only one. This is going to be the preachy “and you should donate too!” section you were dreading all along, but I’m not going to make a lot of positive arguments. If 90% of the people who answer yes on those surveys are lying to feel good, then only 3 - 5% really want to donate. But bringing the donation rate from 0.0001% of people to 3 - 5% of people would solve the kidney shortage many times over. The point isn’t to drag anti-donation-extremists kicking and screaming to the operating table. The point is to reach the people who already want to do it, and make them feel comfortable starting the process. 20-year-old me was in that category. The process of making him feel comfortable involved fifteen years of meeting people who already done it. During residency, I met a fellow student doctor who had donated. Later, I got involved in effective altruism, and learned that movement leader Alexander Berger - a guy who can easily direct millions of dollars at whatever cause he wants - had donated his personal kidney as well. Some online friends. Some people I met at conferences. And Dylan Matthews, who I kept crossing paths with (most recently at the Manifest journalism panel). After enough of these people, it no longer felt like something that nobody does, and then I felt like I had psychological permission to do it. (obviously saints can do good things without needing psychological permission first, but not everyone has to be in that category, and I found it easier to get the psychological permission than to self-modify into a saint6.) So I’m mostly not going to argue besides saying: this is a thing I did, it’s a thing hundreds of other people do each year, getting started is as simple as filling out a form, and if it works for you, you should go for it7. When I woke up in the recovery room after surgery, I felt great. Amazing. Content, peaceful, proud of myself. Mostly this was because I was on enough opioids to supply a San Francisco homeless encampment for a month. But probably some of it was also the warm glow of having made a difference or something. That could be you! VIII. The ten of you who will listen to this and donate are great. That brings the kidney shortage down from 40,000 to 39,990/year. Everyone knows we need a systemic solution, and everyone knows what that solution will eventually have to be: financial compensation for kidney donors. But so far they haven’t been able to get together enough of a coalition to overcome the usual cabal of evil bioethicists who thwart every medical advance. My kidney donation “mentor”8 Ned Brooks is starting a new push - the Coalition To Modify NOTA - which proposes a $100,000 refundable tax credit - $10,000 per year for 10 years - for kidney donors. There would be a waiting period and you’d have to get evaluated first, so junkies couldn’t walk in off the street and get $100K to spend on fentanyl. No intermediate company would “profit” off the transaction, and rich people wouldn’t be able to pay directly to jump in line. It would be the same kidney donation system we have now, except the donors get $100,000 back after saving the government $1MM+. (the libertarian in me would normally prefer a free market, but “avoid taxes by selling your organs” also has a certain libertarian appeal) This came up often when I talked to other donors. They all had various motivations, but one of the things they cared about was being able to advocate for these kinds of systemic changes more effectively. I personally have been wanting to push this in an essay here for a while, but it seemed hypocritical to play up the desperate kidney shortage while I still had two kidneys. Now I can support NOTA modification whole-heartedly . . . full-throatedly? . . . it’s weird how many of these adverbs involve claims to still have all of your organs. This is also one of the answers to the question I asked in section IV: how do you balance acts of heroic altruism that everyone will love you for vs. acts of boring autistic altruism that will make everyone hate you, but which will accomplish more good in the end?) Coalition To Modify NOTA is full of previous living kidney donors, who are using the moral clout and recognition they’ve gotten to get attention and change the system in an unglamorous way. I find this an admirable way of squaring the circle: do the flashy heroic things to gain social capital, then spend the social capital on whatever’s ultimately most important. If you get one takeaway from this, let it be that those guys who bought the castle were good guys. Two takeaways, and it’s that plus modify NOTA. Three takeaways, and you should feel permission to (if you want) donate a kidney. You can sign up here.9 Feel free to email me at scott@slatestarcodex.com if you have questions about the process. 1Further perspective: I’m 38, which gives me a 2/million total chance of dying per day. So the likelihood that I would die during my kidney operation equals the likelihood that I would die during a randomly chosen two months of everyday life. 2Maybe, kind of. Our knowledge of how radiation causes cancer comes primarily from Hiroshima and Nagasaki; we can follow survivors who were one mile, two miles, etc, from the center of the blast, calculate how much radiation exposure they sustained, and see how much cancer they got years later. But by the time we’re dealing with CAT scan levels of radiation, cancer levels are so close to background that it’s hard to adjust for possible confounders. So the first scientists to study the problem just drew a line through their high-radiation data points and extended it to the low radiation levels - ie if 1 Sievert caused one thousand extra cancers, probably 1 milli-Sievert would cause one extra cancer. This is called the Linear Dose No Threshold (LDNT) model, and has become a subject of intense and acrimonious debate. Some people think that at some very small dose, radiation stops being bad for you at all. Other people think maybe at low enough doses radiation is good for you - see this claim that the atomic bomb “elongated lifespan” in survivors far enough away from the blast. If this were true, CTs probably wouldn’t increase cancer risk at all. I didn’t consider myself knowledgeable enough to take a firm position, and I noticed eminent scientists on both sides, so I am using the more cautious estimate here. 3I told them I had an aunt who died of radiation-induced cancer. It’s true, but I feel grubby for bringing her into this; I thought doctors would be more likely to listen to an emotional story than cold logic. 4EAs have been debating the exact effectiveness of kidney donations for a long time. You can find good skeptical arguments by Jeff Kaufman and Derek Shiller, and good arguments in favor by Alexander Berger and Tom Ash. 5Outside of Philosophy 101 thought experiments, there’s a nonprofit that will often reimburse you for lost wages from your donation. 6Self-modifying into a person who can act boldly without social permission is a more general solution and has many other advantages. But the long version involves living a full life of accumulating moral wisdom, and the short version starts with removing guardrails that are there for good reasons. 7But here are some practical points you might not already appreciate: You shouldn’t have to pay much money. If, like me, you need to travel (eg to New York), kidney related charities will reimburse your travel costs (in theory, I haven’t yet proven this, and a few costs were illegible and I decided not to submit them).
January 17, 2025 · Original source
This is especially surprising because A16Z is famous for going all in on crypto early. But during the 2015 - 2018 period, Bitcoin - the absolute dumbest and most obvious crypto bet - went up 2,000%. So how is performance this bad even possible? The Twitter thread speculates that just as Uber used to happily lose money on every ride in order to gain market share, A16Z is happily losing money on every investment in order to gain VC market share. But ride-sharing is a natural monopoly; how will A16Z prevent competitors from entering venture capital? And why should people give it any market share at all if it can’t make them money? Maybe their pitch could be that you’ll make less money, but it will be uncorrelated with the regular stock market? But is that true? Aren’t tech startups pretty cyclical? Also, I wonder if this was framed to their LPs as “yeah we’ll definitely lose your money for the first ten years, but eventually it’ll all work out”. They must be the most trusting people in the world.
February 05, 2026 · Original source
9: @abio: “DC has a rideshare app called Empower that charges 20-40% less than Uber. (Drivers like it too because they keep 100% of the fare)...DC is trying to shut it down because of liability insurance. DC law requires $1 million per ride. The $1 million requirement isn’t sized to typical accidents. When $100,000 is the limit available for an insurance claim, 96% of personal auto claims settle below $100,000...Empower can offer $7 rides partly because it circumvents the mandate. DC is shutting it down for exactly that reason.”
42: An AI Generated Reddit Post Fooled Half The Internet. Someone claiming to be a software engineer at a food delivery company (maybe DoorDash or UberEats) talked about all the evil tricks they used to exploit drivers and customers. But on closer inspection, their story fell apart and they didn’t work for a company like this at all. I’m surprised by the arc of this story, not because the original post was convincing (it wasn’t), but because I assumed DoorDash and UberEats did things approximately this evil, but everyone acted like the fake leak was shocking (including real DoorDash and UberEats employees). Also, it’s pretty funny that in a world where everyone is worried about fake AI-generated photos and videos, the record for most successful deceptive AI-generated content is still ordinary text.
48: Also from Changing Lanes: Whatever Happened To The Uber Bezzle? A couple years ago, everyone in tech journalism was writing about Uber was a “bezzle”, a made-to-order Cory Doctorow coinage which meant it was a giant obvious Ponzi scheme that would finally reveal the entire tech industry as an emperor without clothes when it inevitably collapsed. Now Uber is doing better than ever and making billions in profits. So what happened? Obviously they stopped subsidizing their rides and raised prices until revenue > cost, but how come the bezzlers thought they couldn’t do that, and why were they wrong? Andrew says the bezzle thesis had assumed that the government would crack down on the gig economy (it didn’t; Uber had good lobbyists and voters liked cheap foods and rides), and that there would be an infinite number of would-be competitors moving in to take market share as soon as Uber raised prices (there weren’t; Uber bullied everyone except Lyft out of the market, and Lyft and Uber would rather play nicely together than compete each other down to zero marginal profit). Oh well, I’m sure tech journalists are right about everything else being a giant Ponzi scheme that will inevitably collapse and reveal the entire tech industry to be an emperor without clothes.
fluvoxamine

fluvoxamine is a recurring brand in the Astral Codex Ten archive, appearing 7 times across 7 issues between February 16, 2021 and February 01, 2022. The archive places it in contexts such as "treating severe COVID (with eg ivermectin, fluvoxamine)"; "people have been manufacturing fluvoxamine for years"; "Corticosteroids, fluvoxamine, and Paxlovid seem provisionally great". It most often appears alongside COVID, FDA, ivermectin.

Article page
fluvoxamine
Mention count
7
Issue count
7
First seen
February 16, 2021
Last seen
February 01, 2022
February 16, 2021 · Original source
When the fifth wave strikes in late spring/early summer, some of the population (~50%?) will be vaccinated, another part of the population (~25%?) will have had the disease already, and the rest (~25%?) will be completely vulnerable. The new strains will probably cause a limited number of mild cases among the vaccinated/resistant, and a larger number of more severe cases among the vulnerable. Either way, the presence of the larger vaccinated/resistant contingent could potentially make this less severe than previous waves. Also, we may have learned more about treating severe COVID (with eg ivermectin, fluvoxamine), which might further decrease deaths.
November 23, 2021 · Original source
Note that this really only applies to new chemical entities; people have been manufacturing fluvoxamine for years and its probably well understood by now. Not always true though; we saw a worst-case situation recently with the ranitidine withdrawal: a medicine that some reasonably healthy people take every day of their lives was shown to be contaminated with small amounts of a nasty carcinogen. If Pfizer happened to have some gaps in their understanding for the Paxlovid process, the FDA might go easy on them as dying of Covid now is worse than a slightly increased risk of cancer in the future, but it takes time to review all of these risks and make a justified decision.
November 23, 2021 · Original source
This is false and I don't know where they're getting it from. Corticosteroids, fluvoxamine, and Paxlovid seem provisionally great. I haven't looked into the monoclonal antibodies but if western health authorities say they're fine I have no reason to doubt that. I even think there are plausible arguments (though no proof) for a few less-used options like zinc.
Obviously I urge my readers to get good treatments and not bad treatments. In fact, you even have my permission to pester your doctor about giving you a fluvoxamine prescription if you're in the appropriate stage of COVID and they don't think of it themselves. If they tell you it might have dangerous side effects, tell them that I have more experience with it than they do, and no it doesn't (unless you are bipolar or in some kind of special bizarre high-risk category).
I do think it’s occasionally possible to have genuine bottom-up medical research: ketamine seems to have worked this way. Even the trials that found fluvoxamine worked were funded by a random billionaire, which is sort of bottom-up in the sense of not being some established clique of experts with a vested outcome in the result. But I don’t think we know how to do this consistently yet, even though it would be cool if we could.
November 25, 2021 · Original source
Boris Johnson (left) is 5’9, so the guy in the middle must be gigantic. Who is he? Looks like it’s Milo Djukanovic, President of Montenegro, who’s 6’6 (198 cm). Is he the tallest world leader? It seems like he’s tied with his colleague across the border, Serbian president Aleksandar Vucic. Why are Balkan leaders so tall? As usual, the answer is “genetics”. This article says: It has been noted that men from Herzegovina are taller on average than men in other places—the average male height is just over six feet...Putting all the data together, researchers concluded that the most likely cause of larger-than-average height of Herzegovinian men is lifestyle during the Paleolithic—men hunted large animals such as mammoth for survival—such a diet, heavy in protein, combined with small population densities, would have provided ideal conditions for height selection, resulting in increasingly taller men who passed the trait down through their I-M170 chromosome to future generations. Some sources note that they manage to beat the Dutch despite the latter country’s much higher human development index. The Dutch are probably tall through a combination of nature and nurture; Balkan people are tall through nature alone. 7: Eliezer Yudkowsky doesn’t need more ego boosts, but an idea he had a couple of years ago - using strings of bright lights to provide a better and brighter experience for Seasonal Affective Disorder sufferers than regular light boxes - spread from him to the rationalist community to the wider world, and has finally gotten tested in a formal study (see Acknowledgments section). Results seem vaguely positive: "SAD symptoms of both groups improved similarly and considerably...exploratory analyses indicate that a higher illuminance is associated with a larger symptom improvement in the BROAD light therapy group" 8: Percent of people who choose woke options on polls very tentatively and preliminarily seems to be going down post-Trump (h/t Richard Hanania). 9: Twitter conspiracy theories 10: Did you know: all those reconstructions of “how classical art would have looked with the original paint” are probably inaccurate. There is no reason to think the Greeks and Romans used garish technicolor hues on their statues; what evidence we have suggest they were good at shading, and the statues were probably colored very tastefully. 11: Complaints about how Karl Friston uses the term “Markov blanket” 12: Trevor Klee on the claim that cyclosporine patients don’t get dementia. Apparently there was a big study where basically nobody on the immunosuppressant cyclosporine ever got dementia, and there are some theoretical reasons why cyclosporine might prevent neurodegeneration. But another study found people on cyclosporine got dementia at the usual rate. I think in a situation like this you should have a really high prior on “the people who got the crazy result bungled their study somehow”, but I’m interested in hearing what other people think. 13: Also from Trevor: a history of fluvoxamine treatment for COVID. 14: To tide you over until the next book review contest, here is awanderingmind’s review of The Conquest Of Bread. 15: Claims: cnbc.com/2021/11/05/sam…\nft.com/content/dcb75a… (better article, but paywalled)","username":"moskov","name":"Dustin Moskovitz","profile_image_url":"","date":"Fri Nov 05 15:49:46 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":184,"like_count":1188,"impression_count":0,"expanded_url":{"url":"https://www.ft.com/content/dcb75a56-ca23-439c-96db-56483979bf34","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/80a58c96-c72f-4301-b571-aa9384f132bd_2400x1350.jpeg","title":"Subscribe to read | Financial Times","description":"News, analysis and comment from the Financial Times, the worldʼs leading global business publication","domain":"ft.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> 16: Big trial on Vitamin D for depression finds null result. Peter Attia tries to tear it apart here, but I am unconvinced, especially in the context of Vitamin D never working for any of the things people say it does besides the most boring aspects of bone health. 17: “California is actively considering the adoption of flawed and inequitable guidance on math curricula based on misleading data and inaccurate success metrics reported by San Francisco Unified School District (SFUSD)...Based on our review of the data, we found misleading, unsupported, and cherry-picked assertions of success for the new math program. We noted that overall test scores are down and enrollments in UC-approved advanced math classes have dropped as well.” It looks like San Francisco is trying the good old “lower standards, then when more kids meet the standards, claim your school reform plan worked” trick again. 18: A new study claims that self-reported “Long COVID” symptoms are more associated with believing you’ve had COVID than with actually having it (as measured by serologic testing), which sounds like pretty strong evidence that it’s psychsomatic. Expert reactions are mixed-to-negative, although the only one of these that doesn’t sound like excuse-making is Dr. Rossman’s about the unreliability of the tests. I haven’t confirmed test reliability stats but Philippe Lemoine also thinks this is a plausible confounder. 19: Noahpinion: What If Xi Jinping Just Isn’t That Competent? I appreciated this for making me think, and for underlining the extent of the difference between the Deng/Jiang/Hu era and what Xi’s doing. I especially appreciated this line, which I’d never thought about before: Xi presided over the end of China’s hypergrowth. To some extent this is not his fault. No country can grow at 10% forever, and there were many structural forces pushing downward on China’s numbers — the end of the demographic dividend, the exhaustion of rural surplus labor (the Lewis Turning Point), the saturation of export markets, and so on. But China is also slowing down earlier than South Korea, Taiwan, or Japan did in their day. China’s per capita GDP (at PPP) is still only about 1/3 that of a developed country, so if they stop catching up at about half of developed-country levels, that will not be a great showing. A big lesson of the past twenty years has been “actually liberal democracy isn’t necessary to reach developed-country status”, so it would be quite the twist if it turned out you needed liberal democracy to reach developed-country status. This gets pretty close to the great mystery of why some less-developed countries “catch up” and others don’t; whatever happens in China is going to be a really useful data point. 20: Variations on the fable of The Frog And The Scorpion. 21: You’ve probably heard about the University of Austin, the new project by a bunch of wokeness-critical academics to start a new university that won’t cancel people or force conformity (New York Post article, Politico article - these were the two least “you need to be super-outraged about this right now” articles I could find). Tyler Cowen and Larry Summers are involved; Steven Pinker was supposed to be but left for unclear reasons. My thoughts, in no particular order: Even forgetting the political aspect, attempts to start new universities are always welcome.
December 22, 2021 · Original source
Here’s my pitch for fluvoxamine (Luvox) for COVID.
But a different drug, the SSRI antidepressant fluvoxamine, actually did really well! It decreased COVID hospitalizations by about 30% - not the perfect cure rate the rumors attributed to ivermectin, but a substantial decrease. Given the size and professionalism of this study, and another smaller one that also got positive results, I and many others take Luvox pretty seriously. At this point I’d give it 60-40 it works.
What are the risks? Like every medication, including Tylenol, aspirin, etc, Luvox has some common minor side effects and some rare major ones. But let’s step back a second. Fluvoxamine is a bog-standard SSRI. Its side effects are generic SSRI side effects. We give SSRIs to 30 million people a year, or about 10% of all Americans. As a psychiatrist, I’m not supposed to say flippant things like “we give SSRIs out like candy”. We do careful risk-benefit analysis and when appropriate we screen patients for various risk factors. But after we do all that stuff, we give them to 10% of Americans, compared to 12% of Americans who got candy last Halloween. So you can draw your own conclusion about how severe we think the risks are.
December 22, 2021 · Original source
In my post yesterday, I quoted a Vox article describing work by Dr. Ed Mills and others to get the FDA to approve Luvox for COVID. As of that point, the FDA didn’t know how to process an application without a sponsoring drug company:
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
But it looks like just as I published, he and his colleagues found a way around the problem: #IDTwitter we submitted EUA Application for #Fluvoxamine for #COVID19 to @US_FDA with the assistance of @EricLenze2 @AngelaReiersen @drklausner @ShohamTxID, and Ed Mills \nIf you want to sign a letter of support forms.gle/3mDgxxgMgtVDNS…\n(names are not public &amp; will be reviewed) ","username":"boulware_dr","name":"David Boulware, MD MPH","profile_image_url":"","date":"Tue Dec 21 21:14:24 +0000 2021","photos":[],"quoted_tweet":{"full_text":"#IDTwitter For those in the medical community who would want to sign on to a letter of support for @US_FDA EUA Application for #Fluvoxamine please go here: https://t.co/7K0OCSSm3O \n\n(I ask others to not spam this, as this creates more work for me in reviewing the list).","username":"boulware_dr","name":"David Boulware, MD MPH"},"reply_count":0,"retweet_count":36,"like_count":122,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":false}" data-component-name="Twitter2ToDOM"> …though so far I’m having trouble figuring out their exact strategy:
February 01, 2022 · Original source
COVID 22. Fewer than 10K daily average official COVID cases in US in December 2022: 20% 23. Fewer than 50K daily average COVID cases worldwide in December 2022: 1% 24. >66% US population fully vaccinated (by current standards) against COVID: 70% 25. India's official case count is higher than US: 5% 26. Medical establishment reverses course and officially says any of Vitamin D, HCQ, or ivermectin is actually effective against COVID: 1% 27: FDA approves a COVID indication for fluvoxamine: 60% 28. Some new variant not currently known is greater than 25% of cases: 60% 29. Most people I see in the local grocery store 12/31/22 are wearing masks: 60% 30. Masks still required on domestic flights: 60% 31. CDC recommends that triple-vaxxed people get at least one more vax: 70% 32. China has fewer than 100,000 COVID cases this year (official estimate): 30%
Ford

Ford is a recurring brand in the Astral Codex Ten archive, appearing 7 times across 7 issues between March 25, 2021 and April 08, 2025. The archive places it in contexts such as "Distribution 1 represents car companies in your region. Again, it has low variance, so they're all pretty similar. Ford vs. GM"; "If Ford refuses to sell cars to black people"; "family’s purchase of a Ford tractor". It most often appears alongside Tesla, America, China.

Article page
Ford
Mention count
7
Issue count
7
First seen
March 25, 2021
Last seen
April 08, 2025
March 25, 2021 · Original source
Okay, now suppose that Distribution 1 represents car companies in your region. Again, it has low variance, so they're all pretty similar. Ford vs. GM, something like that.
What about Distribution 2? Now Point B is Tesla, making revolutionary new environmentally-friendly cars. In fact, let's say it's some super-Tesla that's even better than the real Tesla, plus their cars are affordable even for the poorest people. Point A is Yugo (or if you know a more modern example of a terrible car company, use that). Now which distribution would you rather have?
Diversity libertarianism is usually in favor of companies being allowed to do a wide range of things, because it ensures everyone will be well-served. If you assume an arbitrarily large number of uncorrelated companies, then whatever the thing you want is, there's at least one existing or easy-to-start company doing it. If Ford refuses to sell cars to black people, Toyota should see a profit opportunity and step in. If both Ford and Toyota ban blacks at the same time, some upstart like Tesla should step in. If Ford, Toyota, and Tesla all do it, some guy with a wrench who's always dreamed of making cars in his garage should notice a billion-dollar business opportunity lying on the ground, get seed capital from equally greedy investors, and solve the problem.
April 30, 2021 · Original source
Borlaug’s section, in contrast, begins not in the rarefied world of middle-class New York, but on the unforgiving prairie of Saude, Iowa, which his poor Norwegian immigrant family tries to farm. He comes of age at roughly the same time as Vogt, but his early life may as well be mid-1800s Little House on the Prairie: Borlaug and his siblings literally have to walk three miles in the snow to get to their one-room schoolhouse. Fortunately, he is freed from a life of subsistence farming and given the chance to go to high school and college by his family’s purchase of a Ford tractor, which nicely sets up his lifelong optimism about the ability of technology to improve lives. While attending college in Minneapolis at the height of the Great Depression, Borlaug sees a crowd of striking dairy farmers being beaten by police and National Guardsmen for protesting the drop in the price of milk by surrounding a scab-driven milk truck. "Not all of the shouting men were farmers, Borlaug realized," Mann writes. "Some of them were just hungry – famished men, women, and children, almost maddened by want." Where Vogt might have curled his lip in distaste and gone home to write a pamphlet about this scene as an illustration of humanity’s taxing the earth’s carrying capacity and reaping the consequences, for Borlaug this was the catalyst for homing in on solving the problem of hunger. Mann: "Something must be done, he thought. Those famished people were ready to tear apart the world, and who could blame them? Here began, or so he said afterward, the work that would make him the original Wizard."
June 04, 2021 · Original source
1. Barefoot. Unable even to afford shoes, they must walk everywhere they go. Income $1 per day. One billion people are at Level 1.
Flying cars didn’t have the same issues; they were being developed privately. But regulation doomed them. Harold Pitcairn was almost successful in developing a flying car, but then in World War II the government nationalized his helicopter patents (they promised to give them back after the war, but reneged) and he spent the rest of his life in court. He won, 17 years after his death. Bruce Hallock had a promising design, but he sold a plane to a missionary group in Peru and was arrested as an “arms trafficker”. Robert Fulton had a successful prototype, “however, Fulton’s financial backers had become discouraged with the seemingly endless expense of meeting government production standards, and they withdrew their support.” Molt Taylor “was actually in serious negotiations with Ford as late as 1975 to have the Aerocar mass-produced. The monkeywrench was thrown into the negotiations by the FAA and the DOT. Taylor already had an airworthiness certificate for the Aerocar, granted by the CAA (predecessor of the FAA) after a delay of 7 years from its first flight. He claims that the agencies turned thumbs down on the Aerocar ‘because everybody would have one, and we couldn’t handle the [air] traffic.’ Airplane regulation has only gotten stricter: “The entire F.A.R. / A.I.M., which every airman is responsible for knowing, is 1085 pages long. At least it was in 2013; a new one comes out every year.” So in the end, we have none of these technologies. No flying cars, even though they were prototyped almost a hundred years ago. Some nuclear energy, but crippled, aged, feared, and hated. 3D printing, but no nanotech. No level 5. Because the state needs legibility, and progress is not legible. The bureaucratic incentives are to calcify. If no one does anything new, no one will do anything wrong. Hall:
June 28, 2021 · Original source
Imagine having to start your own car company in Zimbabwe. Your past experience is "peasant farmer". You have no idea how to make cars. The local financial system can muster up only a few million dollars in seed funding, and the local manufacturing expertise is limited to a handful of engineers who have just returned from foreign universities. Maybe if you're very lucky you can eventually succeed at making cars that run at all. But there's no way you'll be able to outcompete Ford, Toyota, and Tesla. All these companies have billions of dollars and some of the smartest people in the world working for them, plus decades of practice and lots of proprietary technology. Your cars will inevitably be worse and more expensive than theirs. Every country that's solved this problem and started a local car industry has done so by putting high tariffs on foreign cars. Locals will have to buy your cars, so even if you're not exactly making a profit after a few years, at least you're not completely useless either.
August 25, 2021 · Original source
Offset your carbon emissions if you can afford it
30. https://www.engineeringnews.co.za/article/ford-hits-carbon-emissions-reduction-target-eight-years-early-2018-07-27/rep_id:4136 . Good information on Ford was hard to find, but I'm calculating this based on their claim that they reduced emissions by 3.2 million metric tons and this corresponds to reaching their goal of decreasing emissions by 32%. That suggests their original emission level was 10 million tons and so their remaining level is 6.8 million tons. This is just their manufacturing emissions - it doesn't count emissions from the cars they make.
September 18, 2023 · Original source
If you buy Ford you also have to pay off its debt which makes the ratio a little less crazy. "Ford Motor long term debt for the quarter ending June 30, 2023 was $93.895B, a 10.45% increase year-over-year." vs. "Tesla long term debt for the quarter ending June 30, 2023 was $0.872B, a 69.91% decline year-over-year."
I've worked along former SpaceXers and hung out with current ones (mostly in outdoors sports). If you work in the industry, especially in LA, you run into them. I was also interviewed by Brogan at Hyperloop a while back (super nice guy). The SpaceX hiring bar for technical talent is super high and I wouldn't exaggerate to say the average SpaceX engineer is twice as talented and hardworking as the average Boeing guy. Also, pretty arrogant in my experience (versus Googlers I've met tend to be humble even if they went to Stanford). I think this really started from the top of the company and he couldn't have built this pyramid of insane talent if he didn't have an informed, critical understanding of mechanical engineering.
He got accepted to a Stanford PhD program in engineering
April 08, 2025 · Original source
History provides examples of very fast industrial transitions. For example, during WWII the US converted most civilian industry to a war footing within a few years. The most famous example is Willow Run, where the government asked Ford to build a bomber factory; three years after the original request, it was churning out a bomber per hour.
How did Willow Run move so quickly? It had near-unlimited money, near-unlimited government support, talented people in charge, and the ability to piggyback off Ford’s existing capacity to build and staff factories.
And we predict they get the factories. This is maybe overdetermined - did you know that right now, in 2025, OpenAI’s market cap is higher than all non-Tesla US car companies combined? If they wanted to buy out Ford, they could do it tomorrow.
NVIDIA

NVIDIA is a recurring brand in the Astral Codex Ten archive, appearing 7 times across 7 issues between October 10, 2024 and February 05, 2026. The archive places it in contexts such as "the first stock is NVIDIA"; "NVIDIA? Seems like a good bet for the early stages"; "Biden bans NVIDIA from sending advanced chips to China". It most often appears alongside OpenAI, Anthropic, China.

Article page
NVIDIA
Mention count
7
Issue count
7
First seen
October 10, 2024
Last seen
February 05, 2026
October 10, 2024 · Original source
You can’t see it in the screenshot, but the first stock is NVIDIA, the second TSMC, the third Alphabet, and the fourth Microsoft. On average they went up about 0.5%, on a day when the NASDAQ as a whole also went up about 0.5%.
Should we have expected a single California law to have an effect visible in the markets? According to Daniel and @GroundHogStrat , past history says yes: when California passed a proposition backing down from their attempt to crack down on Uber over gig workers, Uber’s stock went up 35%. If SB 1047 was going to be as bad for AI as the anti-gig-worker rules were for Uber, we would expect a similar jump. Even if the bill would be fine for incumbents but only hurt small startups, we would have expected a hit for NVIDIA, who sells chips to those small startups. But NVIDIA went up less than the NASDAQ overall.
January 02, 2025 · Original source
If we expect the Singularity to grow the economy by orders of magnitude, it might be worth investing in stocks rather than other instruments (eg bonds) that pay out a fixed sum. Are AI stocks better than other stocks? Not obviously - see the classic stories about how the computing revolution failed to enrich IBM, or the Internet revolution failed to enrich Yahoo. NVIDIA? Seems like a good bet for the early stages, but it’s purely intellectual labor and therefore replaceable after superintelligence; at some point you would want to switch to physical capital. All of this seems a lot more dangerous than just investing in index funds; the upside is so high that it seems silly to risk missing it by over-optimizing.
April 15, 2025 · Original source
Homeowners want to preserve or increase the value of their houses. Of these, I think 6 is one of the less important ones - if this were the dominating factor, people would support upzoning, since it usually raises the value of properties in the upzone (if developers can build skyscrapers on your land, then your land value goes up relative to the profitability of skyscrapers). But part of the problem is that people don’t support upzoning. So 6 can’t be the dominating factor. Without POSIWID, people could think about all of these possibilities and come to their own conclusions. POSIWID tries to ban thinking about 1-5 by fiat, insisting that 6 is the only possible explanation and anyone considering the others is naive. I think this makes it a bad heuristic. But there are two more concerning things about how Negating is using POSIWID. First, he’s picking out one particularly salient thing the system does (raise house prices) and claim that’s “the” purpose. He could equally well pick any of the other results - preserve neighborhood character, protect the environment, help Chinese people escape currency controls. Like I said in the original post, in practice POSIWID serves as justification for paranoia - whatever effect you like least, whatever possibility would be most sinister - that’s the one that the system is intentionally aiming for. Second, he’s saying it’s the purpose of “the” system. Which system? I bet whatever government he’s talking about has some organization called the Affordable Housing Bureau, or whatever. And I bet that the Affordable Housing Bureau really does make housing slightly more affordable, relative to the counterfactual where it doesn’t exist. It’s just that lots of other government, market, and social forces conspire to make it much less affordable. If Negating were to claim “The purpose of the Affordable Housing Bureau is to make housing less affordable”, this would be false even if the overall picture (the government is deliberately raising real estate prices) were true. Brad writes: I have to toss in Pournelle's Iron Law. The purpose of a system - when it is first established - may be dramatically different from the purpose it assumes after a few years. Consider: You establish a system to solve a problem. That could be homelessness, or asylum, or drug abuse, or any of a number of other things. This system employs people, who then have an automatic interest - not in solving the problem - but in prolonging it, even in making it worse. After all, without the problem, the organization would not need to exist. And hwold writes: I see it used as "if you have a complex system/bureaucracy to solve X, then the incentives inside it is for X to get worse, and incentives will not have 0 influence on outcomes" For example : https://x.com/Devon_Eriksen_/status/1906042672499864034 I think this sounds profound on first glance, and it’s probably true in some cases. But it’s not nearly true enough to be an Iron Law. Try to think about it in specific Near Mode cases: If you eliminated police, would crime go down, because the police have an incentive to preserve crime? If you eliminated the fire department, would fires go down, because the fire department has an incentive to preserve fire? If you eliminated doctors, would cancer deaths go down, because doctors have an incentive to preserve cancer deaths? If you eliminated the FDA, would dangerous drug side effects go down, because the FDA has an incentive to preserve dangerous drug side effects? If you eliminated the Federal Reserve, would bank runs go down, because the Federal Reserve has an incentive to preserve bank runs? Brad’s original comment mentions homelessness and drug abuse, but I know some drug abuse doctors, and they’re (mostly) good people who do their best in a tough situation. Drug abuse doesn’t continue because drug abuse doctors are secretly ensuring it continues to help their bottom line. Drug abuse continues because fentanyl is really, really addictive. Even good conspiracy theories don’t work like this. Was there a conspiracy among pain pill manufacturers to addict people? Yeah, kinda, although I think the degree to which this caused the opioid crisis is pretty overblown. But the pain pill manufacturers weren’t a system dedicated to preventing addiction. They did their job (reduce pain) fine, then ran an unrelated evil conspiracy on the side! Breb writes: This way of thinking may result from taking a strategy for predicting the motives of individuals, and using it to predict the motives of organisations. "Cui bono?" works when you're considering a single action carried out by a single person at a single moment in time, but it doesn't really work when you're considering the behaviour of hundreds of people who are incentivised to somewhat-but-not-perfectly cooperate over a long period to somewhat-but-not-perfectly implement a goal that was established by someone who somewhat-but-not-perfectly understands that that goal is just an instrument to attain a larger, more complex goal set by somebody else. I’m against this for individuals too! There are a million self-help gurus who try to convince you that that if you procrastinate - let’s say you always do term papers the night before and get terrible grades and it’s threatening your ability to complete college - then it must be because this secretly benefits you in some way. Maybe your overly-strict father wants you to complete college, and you’re deliberately trying to fail as a secret act of rebellion against him hidden even from yourself. Although something like this might sometimes be true, more often a clearer understanding of the circuitry involved (in this case, hyperbolic discounting) saves you from these labyrinths and lets you think about things straightforwardly again. Tom J writes: In the original Stafford Beer sense, the slogan POSIWID means that you can't tell from outside the system whether any given behaviour was *intended* or not. For the purposes of objective analysis, you have to treat your system as a black box that *does* whatever it's observed to do, as opposed to what people *claim* the point of the system is. This may be true in cybernetics. Or it may be an interesting methodological commitment, in the same way that the behaviorists’ “assume there is no such thing as human interiority” was an interesting methodological commitment. But I don’t think it’s common or valuable in normal-life analysis of social systems. When Biden bans NVIDIA from sending advanced chips to China, black box analysis would have to be ambivalent between explanations like: Biden personally hates Jensen Huang and wants his company to suffer
Biden thinks NVIDIA produces bad chips and wants to save China from buying inferior products.
October 30, 2025 · Original source
41: Related: NVIDIA is emerging as a new villain in US tech policy; they really want to be allowed to sell advanced technology to China, and are swinging their weight as World’s Largest Company to undermine anyone who who raises national security objections. David Cowan makes the case here: NVIDIA Is A National Security Risk. Steven Adler goes further, saying there is “widespread fear” among think tank researchers who publish work against NVIDIA’s interests. You would think that whatever the disadvantages of having an super-nationalist America First administration in power, at least they would be strongly against handing key military tech to rivals - but it’s not clear which way this will end up going.
November 26, 2025 · Original source
Compute: America is far ahead. We have better chips (thanks, NVIDIA) and can produce many more of them (thanks, TSMC). Our recent capex boom, where companies like Google and Microsoft spend hundreds of billions of dollars on data centers, has no Chinese equivalent. By the simplest measure - total FLOPs on each sides - we have 10x as much compute as China, and our advantage is growing every day. A 10x compute advantage corresponds to about a 1-2 year time advantage, or an 0.5 - 1 generation advantage (eg GPT-4 to GPT-5).
It gets worse. NVIDIA, America’s biggest company, constantly lobbies to be allowed to sell its advanced chips to China. It’s not afraid to play dirty, and stands accused of trying to get China hawks pushed out of government for resisting; Steven Adler reports “widespread fear among think tank researchers and policy experts who publish work against NVIDIA’s interests”. Foundation for American Innovation fellow David Cowan goes further, saying that “NVIDIA is a national security risk”.
All of this lobbying has paid off: the administration keeps proposing changing the rules to allow direct chip sales to China. So far cooler heads have prevailed each time, but the deal keeps popping back onto the table. NVIDIA tries to argue that the models being proposed for export are only second-rate chips that won’t affect the compute balance, but this is false - last month’s talks involved the most price-performant chip on the market. Here’s IFP’s calculation for how caving on this issue would affect the AI race:
January 13, 2026 · Original source
“Oh goodness no, I’m scared of commitment and I work at NVIDIA. I’m going to keep stringing her along forever.”
“Cause, uh, NVIDIA gave OpenAI ten trillion dollars to invest in Oracle conditional on Oracle investing in Broadcom conditional on Broadcom funding the Series A of a vehicle that buys OpenAI stock in exchange for OpenAI backstopping AMD investing ten trillion dollars into us, and every company in the chain had its stock go up 80% on the news, but if our valuation goes down even for one second then it crashes the global economy. And I’m sure I can solve this eventually, but just, uh, don’t let anybody involved in the global economy hear about this until then, okay?”
February 05, 2026 · Original source
Obvious explanation is the world’s most ham-fisted paid influence campaign by NVIDIA. I, for one, am shocked - shocked! - to hear about a lapse in the ethical standards of our nation’s right-wing Twitter influencers. I hope people in the AL policy world are paying attention.
Bitcoin

Bitcoin is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between February 23, 2021 and March 12, 2024. The archive places it in contexts such as "will Bitcoin outperform the US stock market over the next five years"; "By George, Bitcoin isn't wealth, in case you were wondering"; "Please send them in Bitcoin here: 3Qcm3UJRuFca1fTkf2iPPEkU3PevpzPuwP". It most often appears alongside Bay Area, California, China.

Article page
Bitcoin
Mention count
6
Issue count
6
First seen
February 23, 2021
Last seen
March 12, 2024
February 23, 2021 · Original source
4: Also, will Bitcoin outperform the US stock market over the next five years, at 51%. I started out thinking - of course it's 50-50! By the efficient market hypothesis, if any asset was obviously going to do better than another, people would change the price until it wasn't. But on second thought that's wrong - stocks have a higher than 50% chance of beating treasuries over the same period because of a risk premium. Maybe there's no intuitive way to think about this, you have to have opinions on the underlying fundamentals, and it's only 51% by coincidence?
April 16, 2021 · Original source
Although 2021 seems better than 1879 in absolute material terms, George's complaint still rings true: healthcare and higher education are increasingly unaffordable, inequality is as bad as it ever was, and The Rent Is Too Damn High. And even if all of these measures had improved as well, we still have to contend with a fundamental complaint: how can human civilization have piled up an amount of wealth best described as absolutely banana pants insane, and yetstill have poverty, oppression and cyclical recessions? Yes, greed, evil, and human nature will always be with us, but isn't it weird that we haven't eliminated these economic problems the same way we've eliminated Smallpox, Scurvy, and having to write your scathing polemics about Thomas Jefferson by candlelight with a goose feather? Giving the mic back to George, he closes the chapter with this haunting quote, first written 142 years ago: If there is less deep poverty in San Fran Francisco than in New York, is it not because San Francisco is yet behind new York in all that both cities are striving for? When San Francisco reaches the point where New York now is, who can doubt that there will also be ragged and barefooted children on her streets? I'll just leave this here: Number of Homeless Children in U.S. At All-Time High; California Among Worst States. I. Wages and Capital George insists sloppy terminology leads to sloppy thinking. Naturally, he spends an entire chapter beating words to death to correct this. The Meaning of the Terms Let's start with Wealth. The common usage, both then and now, is "anything with an exchange value." George doesn't like how this mixes dissimilar things. By George, what is wealth? Wealth is produced when Nature's bounty is touched by human labor resulting in a tangible product that is the object of human desire. Labor is required, but the amount and type doesn't matter - George offers the example of simply picking a berry off a bush as an act that transforms nature's gifts into human wealth. Note particularly that human desire is an important requirement of wealth; it doesn't matter how much work someone put into something, if it doesn't gratify human needs or desires in some way, it's not wealth. Speaking of human desire, let's talk about Value. Where does a thing's value come from? The prevailing theory of the day was the Labor Theory of Value which originated with Adam Smith and David Ricardo, which says that Labor is the source of value. The early formulations were a bit ambiguous, here's Smith in Wealth of Nations for instance: The value of any commodity ... is equal to the quantity of labor which it enables him to purchase or command. Labor, therefore, is the real measure of the exchangeable value of all commodities. So... is a thing's value how much labor it takes to make the thing, or how much labor someone's willing to exchange for the thing? Nowadays Labor Theory of Value is most commonly associated with Marx. Marx picks a lane and says the value of something is tied to the amount of "socially necessary labor" required to produce it. George goes the other way: It is never the amount of labor that has been exerted in bringing a thing into being that determines its value, but always the amount of labor that will be rendered in exchange for it. - Henry George, The Science of Political Economy, p. 253 In other words, "a thing's value is whatever someone is willing to pay for it." This is in line with the so-called marginal revolution (the movement, not the blog) and modern theories of value. Labor Labor is the exertion of human beings. It's possible to labor to no avail (try punching a concrete wall), but typically humans labor towards an end, such as gaining wealth. But whether or not we accomplish anything with our efforts, George calls them labor. Labor isn't just making things, by the way – it's also moving or exchanging them. Production Production is labor applied "to the production of wealth." You know, productively. This is all human exertion that isn't punching a concrete wall and rewards you for your efforts with something that fits the definition of wealth. Said wealth is the "product of labor." Wages whatever is received as the result or reward of exertion is "wages." No distinction here is made between blue-collar work and white-collar work – whether one is called "hourly pay" and the other is called "annual salary," George calls them both "wages." It doesn't matter whether you receive them from your boss, from customers, or from nature. If you do work and get something from it, you have received "wages." With those basics under our belt, let's circle back to Wealth: What are some examples of wealth? By George, Gold is wealth. Teddy bears are wealth. Tesla roadsters and candy canes and young adult vampire romance novels are wealth. The same goes for fish you've caught, deer you've hunted, and cool looking rocks you've picked up on your morning walk. The value of these things may differ, but as long as they're tangible, originate in nature, someone ever did a lick of work to make or acquire them, and a human being somewhere desires them for any reason, they're wealth. It gets a little clearer when we ask what isn't wealth. And by George, Money isn't wealth. Articles of gold are wealth because they're tangible things that have been dug up, crafted, and fulfill certain human desires. But paper currency, digital currencies, and other things that aren't inherently valuable but merely represent value are not wealth (outside of putting their physical articles in coin collections or making paper airplanes, and so forth). Now don't get the man wrong, these things are certainly valuable. They're just not wealth. They are certificates that represent claims on wealth. For any computer programmers in the audience, money is a pointer to wealth. Likewise Stocks and Bonds and other financial instruments are not wealth. These are also just claims on wealth. A creditor's title to Debt isn't wealth, either, it's just a claim on the debtor's (typically future) wealth. And, writing as he was not long after the Civil War, George points out that Slaves are not wealth either but, represent "merely the power of one class to appropriate the earnings of another class." Wealth, thus defined, is the terminal "ground truth" bits of the economy, and all the financial layers on top are fancy IOUs that just encode various claims on it. George offers a thought experiment to test if something is wealth: if you produce a pile of gold, fish, or Lego bricks, you've clearly increased the amount of wealth in the world. But if you produce a giant pile of IOUs that just records who owns what and who owes what to whom, it doesn't matter how many of them you pile up or how long the chains of ownership get, you still haven't increased the amount of real wealth in the world. Again, this isn't saying the IOUs aren't valuable, they are. But they're only valuable because they ultimately point to real wealth. If you magically transported everyone over to a hypothetical Earth 2, carrying over all of Earth 1's money and financial instruments but none of Earth 1's tangible wealth, the value of all those IOUs would instantly evaporate. Now what about digital goods? Leaving things like Bitcoin aside for the moment, let's consider the case of a digital image file: By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
February 10, 2022 · Original source
#73: Create A New Kind Of Money And Cities The combination of markets and ideas has reduced suffering somewhat. This trend must continue, but I think a global median income of US$30,000 by 2049 is possible. We just need to teach everybody the same skills that Americans have. To enable this, 2 areas where improvement can be made and no new technology is needed are: a new money, and cities welcome to everyone. A new money is needed because the current financial system is not burdened with the risks it creates. Cities don’t grow like they did in the past. Over a 50 year period at the turn of the twentieth century Detroit grew 10X, whereas in this era the Bay Area has not even doubled its population. Nowadays cities that attract the best talent only attract the best talent. If we had a Hypothetical-Bay-Area-City grow like American cities of the past, it would have a population of around 45 million people and GDP of $4.5 billion. What would an asset be worth if it had a $4.5 billion income stream? A little bit of money and land is needed to make a start, but mostly I need you and your talents. Here is my new Substack with details: https://marketismandidearism.substack.com/p/a-new-money-and-cities-welcome-to . Please sign up to make a global median income of US$30,000 by 2049 a reality. P.S. I am talking money here. Accounting entries. Do not talk to me about Bitcoin. Bitcoin is an attempt at cash. 99.99999% of money transactions are not done with cash, they are done with IOU’s. Please. Spare. Me.
#113: Increase Own Intelligence, Then Write About How My name is David Gretzschel and I want money to increase my own intelligence full-time for about a year. Once I have succeeded (more than I already have), I will teach others how to do this. The benefits of this are obvious. And I already know how to do that for the most part. I have a concrete foundation in the form of a synesthetic encoding scheme, that I can build on. I merely need the time to do an intense amount of training without being distracted by either having a job or not having one and starving. And practice how to use them on various mathematical and computational problems. And a bunch of other things. Details are in the long pitch (see below). So I need 20.000 dollars to not worry about rent and food for that time. Please send them in Bitcoin here: 3Qcm3UJRuFca1fTkf2iPPEkU3PevpzPuwP I certainly would have use for more money, too. (though it'd not be necessary, I don't want to dissuade you from it, if that's an option) So do feel free to shower me with the stuff, if you have it and believe in my cause. (or you only believe in it 10%, but know that the expected value calculation still ends up with a happy face /pascal-mugging) With 10.000 dollars I'd still commit to a year, though that would be a bit tighter than I’d like. The longer pitch is here: https://docs.google.com/document/d/170WETB6enUOzQEzwbwmOCVHz9VkBe4R86rCh_ewvOcg/edit?usp=sharing . If you have further questions/conditions/need more persuasion, send an email to: davidgretzschel@gmail.com
September 02, 2022 · Original source
=3rd: The Internationalists, reviewed by Belos. Belos is working on a new blook titled best of a great lot about system design for effective governance. All three third place winners were within two votes of the others, so I decided to award a joint prize. First place gets $5,000, second place $2,500, all three third places get $1,000 each. Please email me at scott@slatestarcodex.com to tell me how to send you money; your choices are Paypal, Bitcoin, Ethereum, check in the mail, or donation to your favorite charity. Please contact me by October 1 or you lose your prize. The other Finalists were: Consciousness And The Brain, reviewed by Demost. Demost is a university researcher in mathematics, computer science, and neuroscience.
February 20, 2023 · Original source
1. Percent of people in US without health insurance (outside those covered by free government programs) is higher in 2023 than 2018: 80% 2. Health care costs (as % of economy) continue to increase at least as much as before: 70% 3. 1 Bitcoin costs above $1K: 80% 4. …above $10K: 50% 5. …above $100K: 5% 6. Bitcoin is still the highest market cap cryptocurrency: 40% 7. Someone figures out Satoshi’s true identity to my satisfaction: 30% 8. Browser-crypto-mining becomes a big deal and replaces ads on 10%+ of websites: 5%
I don’t think the Officialness Divide or the Ability-To-Circumvent-Regulations Age arrived in any meaningful way. I think I was riding high off the age of Uber and Bitcoin, and expected people to continue to have that level of creative/entrepreneurial spirit, and instead, they didn’t.
ECONOMICS: IDK, stocks went down a lot because of inflation, inflation seems solveable, it'll get solved, interest rates will go down, stocks will go up again? In terms of crypto, I'll repeat what I said on my last crypto post: people have found some good applications for stablecoins, especially in foreign countries and for niche transfers by large actors. I expect that to continue, maybe expand, and in that sense I'm bullish, but all of this will get regulated to the point of total boringness. Ethereum will do fine because stablecoins are built on its chain, Bitcoin will do find because Bitcoin maximalists are like cockroaches and even a nuclear war couldn't kill them, altcoins will mostly not do fine. There will still be some exciting applications for solving coordination problems and protecting privacy, but they will be limited to the same niche groups of cypherpunks who cared about these things before cryptocurrency, and mostly not change the world. An exceptionally good result within this window would look like the same kind of niche that Signal has for communication.
March 12, 2024 · Original source
Crypto is back in the news, with Bitcoin at record highs again. Polymarket is crypto-based, so it shouldn’t be surprising that they have the highest-liquidity and most diverse crypto questions:
Coca-Cola

Coca-Cola is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between February 24, 2021 and March 19, 2026. The archive places it in contexts such as "These are people who drink Coca-Cola (and feel good about themselves for doing so)"; "like how Coca-Cola used to have cocaine in it"; "drink Coca-Cola, The Drink For Individual Unique People". It most often appears alongside America, California, United States.

Article page
Coca-Cola
Mention count
6
Issue count
6
First seen
February 24, 2021
Last seen
March 19, 2026
February 24, 2021 · Original source
Proles do wage labor. High proles are skilled craftspeople like plumbers. Medium and low proles are more typical factory workers. They have a certain kind of freedom, in that they don't have status anxiety and do what they want. But they're also kind of sheep. They really like mass culture - the more branded, the better. These are people who drink Coca-Cola (and feel good about themselves for doing so), visit Disneyland (and accept its mystique at face value), and go on Royal Caribbean cruises. When they hear an ad say a product is good, they think of it as a strong point in favor of buying the product. They feel completely comfortable expressing their opinions, but their opinions tend to be things like "Jesus is Lord!", "USA is number one!", "McDonalds is so great!", and "Go $LOCAL_SPORTS_TEAM!". They are weirdly obsessed with cowboys (Fussell says cowboys represent the idea that poorer people are freer and more authentic than rich office-worker types, plus the West is the prole capital of the USA) and with unicorns (Fussell: "I've spent six months trying to find out exactly why, and I'm finally stumped"). When they have unique quirks, they tend to be things like "collecting lots of Disney memorabilia" or "going powerboating slightly more often than the other proles do". There's also a sort of desperate prole desire to be noticed and individuated, which takes the form of lots of "Personalized X" or "Y with your name on it", and also with making a lot of noise (see: powerboating). Fussell describes the most perfectly prole piece of decor as "a blue flameproof hearthrug with your family name in Gothic letters beneath seven spaced gold stars and above a golden eagle in Federal style".
June 13, 2021 · Original source
4: Comments of the week were on Drug Users Use A Lot Of Drugs, where many people pointed out that cocaine works this way too. Coca tea is an over-the-counter stimulant in Peru, which Zach describes as "so smooth, so much less 'buzzy' than with caffeine, that it seems criminal it's not legal in the US", and Harry Deuchar calculates that the average coca tea drinker in Peru might get about 4 mg of cocaine, whereas the average addict gets about 900 mg a day. This helps put a lot of things in perspective for me, like how Coca-Cola used to have cocaine in it - probably this was completely reasonable and a fine choice! (this last sentence is so not medical advice)
February 16, 2022 · Original source
This is in Hungarian because there was some brouhaha in Hungary that got it to the top of the search engines, and I’m lazy. In one kind of surreal passage, Teach discusses the psychoanalytic interpretation of dreams. Dreams contain content that the mind wants to repress, but then - why dream it? Why go to a psychoanalyst specializing in dream interpretation? When the CIA wants to keep something classified, they don’t cloak it in a riddle and email it to the KGB’s Riddle Decoding Division.
As for you, you’re probably even more contemptible than these Athenians. Teach thinks the modern psyche is downstream of decisions by advertising agencies. At some point their usual trick of selling products through implied peer pressure and hot women stopped paying as many dividends. The companies did some kind of judo move where they told us “well, darn, you’re just too individual and unique a person to fall for a mass advertising campaign - and incidentally the surest way to make everyone understand that is to drink Coca-Cola, The Drink For Individual Unique People”. And everyone lapped it up. This isn’t even subtle, the highest market value company in the world uses the motto “Think Different”. Or Burger King: “Have It Your Way”. Literal actual Coke printed the 150 most popular names onto their bottles in the hopes you would see your name and think you had a special relationship with them.
Teach seems to think something like this can also happen en masse, eg how wokeness originated as a call to destroy the system and ended up as a Coke marketing gimmick.
June 07, 2023 · Original source
On one side is the good America that Wang admires. This is the America that grew from a bunch of tiny colonies under attack by Indians and Redcoats into a technological and economic superpower. It won World War II and the Cold War, and outlasted Maoism in China. It built the Panama Canal, the interstate highways, and the Space Shuttle, but also globally respected corporations like Microsoft and Coca-Cola. Its people are effortlessly patriotic, self-assured, and committed to their Constitution and ideals. Its government runs on meritocracy and everyone respects talent regardless of its social class.
May 07, 2024 · Original source
Take a thing that you don’t want people to be allowed to talk about. For example, maybe Coca-Cola doesn’t want people to talk about how soda makes you fat.
Find some schizos saying a much stronger, extremely offensive thing. For example, “the Jews are adding obesity-promoting chemicals to Coca-Cola in order to destroy the white race”.
Now nobody can talk about how Coca-Cola makes you fat, because people will say “That’s the discredited racist Great Enfattening conspiracy theory, shame on you for platforming that kind of stuff.”
March 19, 2026 · Original source
“I’ll have, uh, the fried chicken, and a Coca-Cola,” he said. The waitress beamed at him. “Great choice. And your guest says he’ll be just a little late.” “My guest?” asked John Rawls Alcoholic. “Don’t worry about it, sweetie,” said the waitress, and went back into the kitchen.
The waitress brought him his fried chicken and a Coke. “Anything for you, sweetie?” she asked John Rawls Brahma. “Coke for me too,” he said, and she retreated back to the kitchen.
John Rawls Alcoholic took another sip of his Coke. “I always thought morality was pointless,” he said, “just another trick the rich play on everyone else. If it can actually make me better off, maybe there’s a reason to do it. And if there’s a reason to do it, I can go back to the Rawls Foundation and pass their screening test and live like a king!”
Coke

Coke is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between August 25, 2021 and March 19, 2026. The archive places it in contexts such as "If you’re otherwise ambivalent between companies (eg Coke vs. Pepsi)"; "ended up as a Coke marketing gimmick"; "one of the projects I worked on was for Coke". It most often appears alongside Pepsi, United States, Abercrombie & Fitch.

Article page
Coke
Mention count
6
Issue count
6
First seen
August 25, 2021
Last seen
March 19, 2026
August 25, 2021 · Original source
If you’re otherwise ambivalent between companies (eg Coke vs. Pepsi), patronize ones that try hard to reduce or offset their carbon footprint.
February 16, 2022 · Original source
This is in Hungarian because there was some brouhaha in Hungary that got it to the top of the search engines, and I’m lazy. In one kind of surreal passage, Teach discusses the psychoanalytic interpretation of dreams. Dreams contain content that the mind wants to repress, but then - why dream it? Why go to a psychoanalyst specializing in dream interpretation? When the CIA wants to keep something classified, they don’t cloak it in a riddle and email it to the KGB’s Riddle Decoding Division.
As for you, you’re probably even more contemptible than these Athenians. Teach thinks the modern psyche is downstream of decisions by advertising agencies. At some point their usual trick of selling products through implied peer pressure and hot women stopped paying as many dividends. The companies did some kind of judo move where they told us “well, darn, you’re just too individual and unique a person to fall for a mass advertising campaign - and incidentally the surest way to make everyone understand that is to drink Coca-Cola, The Drink For Individual Unique People”. And everyone lapped it up. This isn’t even subtle, the highest market value company in the world uses the motto “Think Different”. Or Burger King: “Have It Your Way”. Literal actual Coke printed the 150 most popular names onto their bottles in the hopes you would see your name and think you had a special relationship with them.
Teach seems to think something like this can also happen en masse, eg how wokeness originated as a call to destroy the system and ended up as a Coke marketing gimmick.
April 20, 2022 · Original source
For every Coke ad that plays to woke tropes and aims for associating $2 of sugar water with social goodness, there are hundreds of ads that say things like "Drink Coke, it's good" or "Coke is like balloons" and which never make it to market because they are filtered out as poorly performing by managers and focus groups and regional testing. The ads we see are not brilliant psychoanalytic strategy, they are a mechanical reflection of what the populace most wants them to be.
If Coke ads are woke today, it's not a strategy to appeal to wokeness, it is a reflection that "woke ad #27" outperformed "funny ad #16" in early tests.
This is a very common conception of marketing/advertising which doesn't really reflect reality. Advertisers and adverts in general are far less empirical/objective and far more subjective than this, even in major enterprises. Even digital advertising, which has a much greater data pipeline than mass campaigns like Coke do, is going to have a major human element.
June 29, 2023 · Original source
Liking Pepsi more than Coke. You could think of this as a preference for drinking Pepsi over drinking Coke - or as an internal state marked by a strong repulsion to Coke plus a strong attraction to Pepsi.
Liking Pepsi more than Coke. You could think of this as a preference for drinking Pepsi over drinking Coke - or as an internal state marked by a strong repulsion to Coke plus a strong attraction to Pepsi. In the first two situations, it’s much more natural to use internal-state language, and in the sixth, it’s much more natural to use preference language. The middle three aren’t obvious, which is why we’re having this debate. The Buddhists say desire is suffering, and sometimes this is literally true. An itch is the clearest example; it’s in an almost perfect superposition between raw suffering and pure desire (to scratch yourself). Is it a preference or a constraint? It’s both - a preference to scratch one’s self, and a constraint to be forced to feel suffering if you don’t scratch yourself. While the person may choose whether or not to scratch themselves, they cannot choose whether or not to feel the suffering. Put a gun to their head and say “stop feeling suffering when you don’t scratch yourself” and they will have no choice but to die. It’s possible, although bizarre, to think of normal preferences like the preference for Pepsi over Coke this way. You could say “this person has the constraint that they will feel suffering when they are forced to drink Coke instead of Pepsi”. It’s not very useful. But it’s possible. Whether it’s more useful to think of any given situation as a preference or a constraint depends on things like whether you can easily satisfy the preference, whether the preference is ego-syntonic or ego-dystonic, and whether it seems normal by social standards. Consider Prader-Willi syndrome, caused by damage to a region of chromosome 15. Symptoms tend to include short limbs, mental retardation, and extreme hunger. Here’s how the NYT describes this last problem (content warning for body horror): One result is a heightened, permanent sensation of hunger. “They describe it as physical pain,” Jennifer Miller, an endocrinologist at the University of Florida who treats children with Prader-­Willi, told me. “They feel like they’re going to die if they don’t get food. They’re starving.” Parents must lock their pantries, refrigerators and trash cans, and their children frequently lie and steal to get something to eat. They have been known to memorize credit-card numbers and secretly phone for delivery, use a drill to remove the door from a locked refrigerator and break into a neighbor’s garage and eat, uncooked, an entire frozen pizza. And here’s how it describes one particular patient’s last moments: In 2004, Peter and Gayle Girard held their annual Christmas Eve party for family members at their home in Orlando, Fla. Before dinner, they set out chips, vegetables and dip, shrimp, a bowl of punch and sodas. Their 17-year-old son, Jeremy, had Prader-­Willi, and they often hosted events at their home so he could join in while they kept an eye on him — as they believed they were doing that night. But the next morning, Jeremy’s belly was distended, and he complained of pain. At the emergency room, doctors pumped his stomach, but his condition worsened. A day passed before surgeons discovered that his stomach, which had been distended long enough to lose blood flow and become septic, had ruptured. Jeremy died that night. Only afterward did the Girards learn that other family members saw him eating more than he should have but didn’t alert them. I insist on calling Prader-Willi syndrome a disease, and a serious one, even though the extreme hunger of Prader-Willi is continuous with/shades into the normal hunger where I would like a slice of pizza. My preference for pizza is so easily satisfied that it rarely bothers me. It’s ego syntonic - I am fine with being the sort of person who likes pizza. It’s socially normal - everyone likes pizza. It doesn’t cause much trouble - it wouldn’t improve my life much if I stopped wanting pizza. So I think of it as a preference. If it were otherwise - the extreme hunger of someone with Prader-Willi - it would be more natural to talk about it as a compulsion, a sense of extreme pain inflicted on me when I wasn’t eating enough, something ontologically similar to a stomach flu that also produces extreme pain in the abdominal region. IV. None of this really addresses Caplan’s most recent post, which is, I think, a much worse point. His current post says that either you have to believe that mental illness doesn’t exist and is just voluntary preferences which are stigmatized by society, or you have to believe that homosexuality is objectively a mental illness. Not only are each of these incoherent ideas, they’re not even the same incoherent idea! You could easily accept one of the incoherent ideas and reject the other! Consider the following three positions: Down’s Syndrome is a terrible disease that inflicts vast suffering on its victims. Also it inflicts suffering on society by making people unproductive. We should be very angry about this, and do everything we can do make people with Down’s Syndrome normal.
December 04, 2024 · Original source
It must have been incredibly jarring and impressive, like an embassy from the future. Imagine that you’re Pepsi, Coke just built the glass building, and you’re still in the brick building. Doesn’t seem great.
March 19, 2026 · Original source
“I’ll have, uh, the fried chicken, and a Coca-Cola,” he said. The waitress beamed at him. “Great choice. And your guest says he’ll be just a little late.” “My guest?” asked John Rawls Alcoholic. “Don’t worry about it, sweetie,” said the waitress, and went back into the kitchen.
The waitress brought him his fried chicken and a Coke. “Anything for you, sweetie?” she asked John Rawls Brahma. “Coke for me too,” he said, and she retreated back to the kitchen.
John Rawls Alcoholic took another sip of his Coke. “I always thought morality was pointless,” he said, “just another trick the rich play on everyone else. If it can actually make me better off, maybe there’s a reason to do it. And if there’s a reason to do it, I can go back to the Rawls Foundation and pass their screening test and live like a king!”
ketamine

ketamine is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between February 13, 2021 and November 14, 2023. The archive places it in contexts such as "That would mean ketamine and psychedelics"; "Ketamine is – well, we are still trying to figure out exactly what ketamine is, but it seems to work"; "Nothing else except maybe ketamine had produced results like this before". It most often appears alongside FDA, SSRIs, US.

Article page
ketamine
Mention count
6
Issue count
6
First seen
February 13, 2021
Last seen
November 14, 2023
February 13, 2021 · Original source
Fourth, what do we know about all of this pharmacologically? Priors seem to be encoded in NMDA receptors and their relative strength modulated by 5-HT2A receptors, so if you wanted to downweight priors (and so relatively upweight sensory evidence), you would want NDMA antagonists or 5-HT2A agonists. That would mean ketamine and psychedelics, which is a good match for ketamine-assisted and psychedelic-assisted therapies where you take the relevant drug, then explore a trauma or memory that you're "stuck" on, then find that your explorations have "unstuck" you much more than they would have without the drug. Sensory evidence seems to be something something AMPA receptors, so maybe ampakines would also be helpful here, but I don't know of any sufficiently good ones, except maybe ketamine again.
May 25, 2021 · Original source
If lifestyle changes, medication, and psychotherapy don’t work, there are some more-involved but very powerful strategies for dealing with treatment-resistant depression, including wake therapy, ketamine, transcranial magnetic stimulation, and electroconvulsive therapy.
Ketamine is – well, we are still trying to figure out exactly what ketamine is, but it seems to work. I will have a separate page up soon about ketamine-related options, but I would put it at this point in the treatment algorithm (and not before) because it’s hard to get, and even when it works it’s hard to sustain the effect. Maybe this should be a second-line option and I’m being a coward by putting it so low down.
Polygala tenuifolia is a Chinese herb. It is under investigation as a rapid-onset depression treatment that may act on NMDA and AMPA receptors, perhaps similarly to the rapid-onset depression treatment of ketamine. It is still extremely experimental and has few studies in support, but early anecdotal evidence is optimistic. The only really credible source for it right now is here, and the recommended dose is 100 mg three times a day. Even more than other substances on here, this one should be considered experimental and not left as the mainstay of important depression treatment.
March 08, 2022 · Original source
History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
August 09, 2023 · Original source
[O]verall brain synchronisation was reduced. Usually, certain parts of the brain are active at the same time, firing electrically together. ‘One part of the brain has a relationship with the activity of another part of the brain in a way that’s predictable,’ Laukkonen says. These parts of the brain are usually communicating with each other, but the new findings suggest that during nirodha-samāpatti that feature quietens down. Similar brain desynchronisation has been observed when people are given anaesthetic doses of propofol or ketamine, but not during sleep.
September 18, 2023 · Original source
Musk does describe sometimes having “terrible lows” and taking ketamine for “depression”. He doesn’t say if this one was diagnosed, but I’m a little skeptical. While granting that he has extremely bad times, an official depression diagnosis requires symptoms other than low mood, including things like fatigue, feelings of worthlessness, loss of interest in doing anything, moving slowly, cognitive impairment, and even suicidal thoughts. More important, it requires that the person not have hypomanic symptoms at the time. Also, it has to last at least two weeks, pretty constantly. Do we have evidence that Musk has been fatigued and felt worthless and just wanted to lie around in bed and not cared about Mars or anything for two straight weeks? I don’t know, maybe he has! I just don’t think the fact that he’s “haunted by demons” and sometimes goes into rages necessarily establishes this. I would guess that Musk’s bad moods happen when something is going wrong in his life, last days-to-weeks instead of weeks-to-months, and are marked by high energy (even if that’s angry/nervous energy). These could be any of a number of things - borderline, autism, narcissism, normal bad moods - but they don’t really match depression.
How would the world look any different to you than it does now if Musk did have depressive phases lasting a month, of the sort he self-medicates with the ketamine he's known to use (not to mention whatever stims or drugs he may be self-medicating with), where he mostly shit-tweeted while folks like Gwynne Shotwell continued to run SpaceX and Zach Kirkhorn ran Tesla (as they always have while doing their best to stop the techno-emperor man-child from follies like rolling out the next Tesla car without a steering wheel because 'FSD is going to work real soon now')?
November 14, 2023 · Original source
The psychiatric study everyone’s talking about this month is ”Randomized trial of ketamine masked by surgical anesthesia in patients with depression”.
Ketamine is a dissociative drug - it produces weird drug effects like feelings of bodylessness and ego death. Recent research suggests it’s a powerful antidepressant. Usually we would try to run placebo-controlled trials. But it’s hard to run a placebo controlled trial of a dissociative. Either you feel bodylessness and ego death (in which case you know you’re getting the real drug) or you don’t (in which case you know you’re in the placebo group). Sometimes researchers try to use an “active placebo” like midazolam - a drug that makes you feel weird and floaty. But weird and floaty feels different from bodyless and ego-dead.
The authors of the recent study go further. They recruited depressed patients who were going into the hospital for routine surgery requiring anaesthesia. When they were anaesthesized, they gave them either ketamine or placebo. Then after they woke up, the researchers asked the patients how depressed they were. These patients had no way of telling whether they got ketamine or not (since they were unconscious at the time). Here are the results:
Microsoft

Microsoft is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between September 22, 2022 and March 03, 2026. The archive places it in contexts such as "The last big antitrust case involved Microsoft"; "before Microsoft and Amazon were a thing"; "globally respected corporations like Microsoft and Coca-Cola". It most often appears alongside Amazon, Amazon, effective altruism.

Article page
Microsoft
Mention count
6
Issue count
6
First seen
September 22, 2022
Last seen
March 03, 2026
September 22, 2022 · Original source
The last big antitrust case involved Microsoft. When IBM got sick of antitrust fights, they decided to outsource the operating system for their PCs. This was like throwing a monopoly bouquet at a wedding and Bill Gates was the bridesmaid who jumped highest and snatched the prize. His plan was to leverage this operating system monopoly into an internet monopoly, and the scheme was working before the Clinton administration sued. The reason I am writing this on Substack and not some Microsoft comment board is because of an antitrust lawsuit.
I’m still not sure about this line of thought. How is this situation? Do we think Mark Zuckerberg wouldn’t have founded Facebook, or Bill Gates Microsoft, if he could only get $1 billion? Can people really tell the difference between $10 billion and $100 billion? Has Jeff Bezos even spent $10 billion?
May 19, 2023 · Original source
When people argue against separatism, they often tout the benefits of being large. A Canada that would be split in two would mean smaller markets, and a weaker political counterweight to the United States. (Not to be mean to Canadian readers, but this argument seems delusional to me — I don’t think Americans currently see Canada as a political counterweight of any significance.) It would certainly be less prestigious. Large size, Jacobs says, is associated with power, and we admire power. We love slogans like “unity makes strength.” But after the medium-sized country of Sweden-Norway became the two smaller countries of Sweden and Norway, they both did well. Small size is less powerful, but it has its own advantages, such as nimbleness and ability to fail non-catastrophically. Small size also allows more diversity in cultural and economic matters, and here Jacobs waxes philosophical, pointing out that favoring diversity over uniformity is a recent, post-Enlightenment idea that has not yet been fully embraced in politics. We can see analogs everywhere. Europe, split into numerous small countries from the Middle Ages onward, became far more advanced than China, which has been unified more often than not. The city-states of ancient Greece and Renaissance Italy are seen as golden ages of Western civilization, even if they weren’t part of larger political units and therefore constantly went to war with one another. In business, large companies are impressive and powerful, but people always complain that Google or Microsoft have become stagnant and that the best place to work is tiny startups of about 2 cofounders and 4 employees. In biology, humans are more successful than numerous larger animals, and in terms of raw numbers, small animals like rats or insects are the most successful of all. Jacobs’s point isn’t that smaller is always better. Her point is that the converse statement, “bigger is always better,” is false — despite how intuitive it feels for political entities. Just like we don’t view a small nation like Switzerland or Singapore as a failure of unity, we (and in particular, Canadians) shouldn’t see the secession of a place like Quebec, if it’s done peacefully and democratically, as a failure either. Still, some people in online reviews of the book complain that this argument is a bit thin, especially considering that it serves as the foundation for the later chapters (which are more directly about late 1970s Quebec politics). Sure, small is beautiful, but large states are great for stability, peace, markets, whatever. If the potential benefits of small national size are Jacobs’s strongest argument, then we can breathe a sigh of relief and go back to agreeing that separatism is bad. Pointing out the widespread bias in favor of unified political entities does seem valuable to me, but okay, fair enough. Does Jacobs have deeper reasons why separatism might be a good idea in general? Yes, and for this we go back to the second half of Cities and the Wealth of Nations. Why Nations and Empires Fail Our breathing rate is regulated through a feedback mechanism. Too much carbon dioxide in the blood, or too little oxygen, and the brain stem commands the diaphragm to accelerate breathing. Once the levels are back to normal, the brain stem receives this feedback and slows breathing down again. Now, Jacobs asks, imagine an impossible creature: ten people, all doing their own thing, but whose breathing is somehow regulated by a single brain stem. The feedback the brain stem receives is a consolidated average of everyone’s carbon dioxide and oxygen levels, and the breathing rate the stem decides on is applied to all ten people, regardless of whether they’re sleeping or playing tennis. This, to put it mildly, wouldn’t work. This creature is an analogy, representing a nation. The ten people are its individual cities, and the breathing rate is the cities’ economies. If it sounds like a stupid analogy, that’s because it is: “I have had to propose a preposterous situation,” writes Jacobs, “because systems as structurally flawed as this don’t exist in nature; they wouldn’t last.” Nor do they exist in machines we design; they wouldn’t work. But “nations, from this point of view, don’t work either, yet do exist.” The feedback mechanism that fails to work properly in a nation is currency. A currency always fluctuates according to the exports and imports of the area where it circulates. Let me use the Republic of Venice and its ducat as a toy example, because the coins look nice: Whenever Venice produces something (like salt) and sells it abroad, foreigners need ducats to buy the exports, so the demand for ducats increases. When Venice buys something from abroad, it needs to use foreign currencies, so the demand for ducats decreases. Add up everything that Venice exports and imports, and you get either a trade surplus (more exports than imports) or a trade deficit (more imports than exports), which determines the value of the ducat relative to other currencies. In both cases, a negative feedback loop restores balance over time, just like our brain stem does with carbon dioxide levels. A trade surplus, and therefore a strong ducat, means that when foreigners want Venetian salt, it’s expensive. So Venice’s exports decrease, while imports increase, since Venetians can use their valuable ducats to buy stuff cheaply from abroad. Conversely, a trade deficit makes exports a bargain for foreigners and imports expensive for Venetians. This feedback loop is great. It’s exactly what a city needs to trigger the crucial import replacement process. When exports decrease and a trade deficit begins (maybe because Constantinople found a cheaper source of salt somewhere else), the weak ducat means that Venice is less able to afford the resources and manufactured goods it used to import. The people of Venice don’t want to have less of those goods, though, so they figure out ways to produce some themselves — that is, they do import replacement. Later they will be able to export the output of the newly expanding industries too, strengthening the ducat and continuing the cycle. Currencies, Jacobs explains, function as automatic tariffs (to protect local industry from foreign imports) and automatic export subsidies (to encourage local industry to export). They are “automatic” because of the feedback mechanism. Just like an accelerated breathing rate, they take effect exactly when they are needed — and no longer. … Or so they should, except that import replacement, as we discussed, is a city process. Whereas most currencies are national or supranational. National currencies work well for city-states, like the Republic of Venice or today’s Singapore. But in large nations, which, remember, are not the fundamental unit of economic life, they mess everything up. Take a city like Detroit. When Detroit’s exports (primarily cars) decrease, Detroit gets no feedback about this, because its currency is the United States dollar, and the United States dollar’s value depends on much more than Detroit. It depends on other cities whose foreign exports might be increasing at the moment. And on rural regions that are selling resources like oil abroad. Also, trade between Detroit and other cities that use the United States dollar — i.e., American cities — is structurally unable to provide any feedback whatsoever. So Detroit doesn’t get the signal that it should buy less stuff from other cities and replace the missing imports with local production. Instead, it just declines. Jacobs hypothesizes that this issue of national currencies is at the root of every large country’s economic troubles. It is why nations and empires always centralize everything into one large city, whether that’s Paris, London, Tokyo, or Toronto, or ancient Rome: that city, being the largest, is simply the only one for which national-level currency feedback works fine. The rest of the nation or empire, then, declines. But of course, nations and empires don’t accept this. They care about the economic well-being of their peripheral regions, sometimes out of genuine concern for the people there, sometimes out of fear that they rebel or hold independence referendums. So nations and empires will embark on every possible solution to reverse the decline. All of their solutions will look like good ideas at first, and yet fail at helping the peripheral regions. Worse, these solutions will weaken the cities, thereby destroying the only real wealth of the country and bringing untold hardship for everyone. Eventually the nation or empire will disintegrate, as nations and empires always do, and always will. Jacobs calls these false solutions transactions of decline. She identifies three types, and, content warning, you might not like some of them depending on your political sensibilities. Sustained military production is a transaction of decline. Permanent military bases and garrison towns are a special kind of settlement: they import a lot and export nothing. Superficially, producing weapons and supplies for the military seems like a good deal for some cities — Jacobs gives the example of Seattle, which, before Microsoft and Amazon were a thing, depended mostly on making military aircraft. But because nobody in a military base ever tries to replace those weapons and supplies with their own production, the trade is sterile in terms of economic development. In a sense, the wealth is slowly “drained” from cities. Large empires are especially prone to this: eventually all of their wealth is destined to the military just to keep the empire together.
Sustained military production is a transaction of decline. Permanent military bases and garrison towns are a special kind of settlement: they import a lot and export nothing. Superficially, producing weapons and supplies for the military seems like a good deal for some cities — Jacobs gives the example of Seattle, which, before Microsoft and Amazon were a thing, depended mostly on making military aircraft. But because nobody in a military base ever tries to replace those weapons and supplies with their own production, the trade is sterile in terms of economic development. In a sense, the wealth is slowly “drained” from cities. Large empires are especially prone to this: eventually all of their wealth is destined to the military just to keep the empire together.
June 07, 2023 · Original source
On one side is the good America that Wang admires. This is the America that grew from a bunch of tiny colonies under attack by Indians and Redcoats into a technological and economic superpower. It won World War II and the Cold War, and outlasted Maoism in China. It built the Panama Canal, the interstate highways, and the Space Shuttle, but also globally respected corporations like Microsoft and Coca-Cola. Its people are effortlessly patriotic, self-assured, and committed to their Constitution and ideals. Its government runs on meritocracy and everyone respects talent regardless of its social class.
Americans (especially within a libertarian or neoliberal tradition) tend to think of these as two sides of the same coin. Freedom leads to innovation. The downside of a society where Bill Gates can drop out of Harvard and create Microsoft without anyone’s permission, is a society where someone can drop out of high school and create a drug gang. We’re committed to the Constitution because it guarantees us the right to build a good life however we envision that term.
July 21, 2023 · Original source
We need a framework for thinking about these trades. Lebron’s first law states that we must know ourselves and our motivations for trading before we trade. We tell ourselves many stories, but someone with intellectual honesty – the person with the most alignment between their motivations and actions – will take money from the person who didn’t go through the work to understand their own motivations. There is a reason that Citadel and other hedge funds pay millions of dollars to trade with retail. They know why they are trading: to maximize profit. And the dilettante who “trades for fun” will be eaten alive by a firm with a much better model of a) the world and b) the dilettante themself. Why did I write this book review? To test my intellectual mettle. I could easily have posted this book review elsewhere, but no, I wanted to see how I stack up against other ACX Book Review contest participants. Similarly, this is often the reason people get into trading. One motivation that Lebron explicitly calls out is intellectual validation. You can toil in obscurity for years as an academic. But in trading, there is a quick feedback loop. If your P&L showed $10M last year and the guy sitting next to you showed $8M, you have demonstrated who is “cleverer” and established a clear hierarchy. What lessons here transfer to our daily lives? Like Paul Graham, Lebron encourages us to keep our identities small. He gives the standard decision-making advice to write down your framework and reasoning for why you made a decision at a specific point in time, in order to avoid biases after the fact. This section of the book contained good general advice, but nothing that will be particularly new for the median ACX reader. 2: Adverse Selection You’re never happy with the amount you traded. Now we start to get into the good stuff. Financial markets are an information aggregation mechanism, relying on multiple parties’ beliefs and recursive Bayesian updates of an individual actor’s beliefs based on the beliefs of others2. Market mechanics demonstrate Bayesian beliefs in action. The following quote is quite long, so skip over it if you don’t want to dive deep into the psychology of making a market. I retained it in full because this is quite literally the best description I’ve ever seen of the Bayesian dance between two market makers: “You are a market maker in South African mining companies. Through years of effort and continual improvement, you have built a trading model for the company Veldt Resources. You walk into work one day, ready to set up your trading for the day. It's a stock that doesn't trade much, and usually there are only two market makers: you and another (we'll call her Jo). She's sharp, and she competes well to trade against customer orders that come in. Your model has Veldt valued at 54.35 ZAR (South African rand). You're going to start quoting the stock, so you're about to turn on your machine making a market 54.25 - 54.45 (1000x)3. Before you turn on, you check the current market and notice that Jo has already turned on and she's making her market 53.50 - 54.00 (2000x). If you were to turn on your machine, your market would cross her market, and you would buy 1000 shares from her for 54.00. You now need to make a decision. Whose model do you believe more, yours or Jo's? If you believe yours, you should turn on your machine, trade at 54.00, and expect to make money. If you believe Jo's model, you should adjust your own model parameters to match her market and turn on, making a similar market to hers. What to do? As with many dichotomies, this is a false one. And as with many decision processes, Bayesian reasoning lights the way… …Jo presumably believes Veldt is worth around 53.75 (the average of her bid and offer). But how confident is she in her belief? The width of her market can give you a clue. It's 0.50 ZAR, whereas yours was going to be 0.20 ZAR wide. All other things equal, you should think that Jo only has 40% (0.20/0.50) of the confidence in her fair value as you do in yours. On some absolute scale of confidence, you can say you had a belief-strength of 100 in your fair value of 54.35 (before seeing Jo's market), and Jo has a belief-strength of 40 in her fair value of 53.75 (before seeing yours). And it turns out the weighted average of these two beliefs is quite a reasonable way to combine them: 100/140 * 54.35 + 40/140 * 53.75 = 54.18. Your updated fair value, having seen Jo's market, is thus 54.18 ZAR. This procedure is a quick, heuristic, and reduced version of Bayesian belief-updating, and a good reference on the subject is A.L. Barker's 1995 paper. After updating, you now believe that the stock is worth 54.18. Assuming your trading costs, risk limits, and return requirements are satisfied, buying 1000 shares for 54.00 is a good trade. Naively, you might just put out a 54.00 bid for 1000 shares, trade with half the 2000 share offer, and hope to collect your expected-value ZAR. In practice, however, you might be able to make even more. If Jo is making a 0.50 wide market, maybe she'd be willing to sell lower than 54.00. It's conceivable that if you put out a 53.90 bid for 1000 shares, Jo will sell at that price, and you collect an extra 100 ZAR! Of course, Jo could react differently. She could see your bid and use that information to change her market, in much the same way you did before turning on. These are difficult decisions, ones where experience with the product and the market make a big difference in being able to eke out a little extra edge. Let's play it safe however and pay 54.00 for 1000 shares. You trade, and Jo reacts by immediately canceling her market. This is not an uncommon occurrence in illiquid stocks, especially in emerging markets, so you're not too surprised. You wait a couple of minutes, mentally visualizing Jo in front of her six monitors, evaluating her trade and her model. Finally, she turns back on. Her new market is 53.50 - 54.05 (10000x)! You reason that Jo has seen that someone (you) disagrees with her valuation of the stock. Jo is a good Bayesian like you, and so she has incorporated that information into her model and updated her beliefs about the fair value of the stock. Her updated belief is that she now wants to sell even more stock, at a marginally higher price. Clearly, she almost entirely discounts the information you've communicated to her with your trade. How should you react? It seems fairly clear that, assuming Jo is not a crazy or incompetent market maker (usually a fair assumption), your trade was a bad one. You bought 1000 shares, when in retrospect, you would have wanted to buy much less, probably zero. Imagine instead that Jo had turned back on with a market of 54.00 - 54.50 (1000x). Her reaction now clearly indicates the information you gave her with your trade is valuable, and she has adjusted her beliefs accordingly. Your trade was probably a good one. Don't you wish you had bought all 2000 shares on offer? No matter what Jo's reaction is, you will be unhappy with your trade. Note that Jo will be unhappy too, since retrospectively she should have either made her initial market bigger or smaller. Welcome to the joyous world of trading!” Whether or not you make money, you have regrets! If you profited, you could have made more. If you lost money, you shouldn’t have made the trade at all. Like death and taxes, you can’t avoid adverse selection. Lebron continues to highlight a few areas of trading that have adverse selection problems. First, IPOs. If you buy the stock in an IPO, you expect the share price to “pop” on the first day of trading. However, if others also have this expectation, the round will be oversubscribed. You can only get the quantity of shares that you bid for when the market doesn’t think the shares will go up. So if you are able to get the shares that you want, the IPO is likely a dud. See also: Venture Capital fundraising. Second, powerful entities that change the rules of the game while you’re playing. Exchanges nullify “erroneous” trades. Brokerages limit buying. Anyone who tried to buy GameStop stock on Robinhood on January 28, 2021, knows this form of adverse selection all too well. Lebron also highlights “special trades”, in which you should throw the “normal rules” out of the window. This advice generalizes to other areas of life: “The normal rules do not apply. If you remove yourself from our usual routine, if you think hard and clearly about the specific situation, maybe you can do something good. Perhaps even great. Others will be paralyzed by inaction, but perhaps you won’t be. Crises can be opportunities.” 3: Risk Take only the risks you’re being paid to take. Hedge the others. In trading, as in life, you can make the right call in expected value terms but still lose due to randomness. Some of that randomness is avoidable. Some of it is not — and can be accounted for by hedging. Here, Lebron encourages us to rely on multiple risk measures and actively seek to understand the risks that we might be subject to. That’s all well and good in the world of finance, with derivatives contracts. But how might this apply in other areas of life? If you work for a publicly traded company and are compensated in stock, sell your shares as soon as you receive them. This is not because I don’t expect the share price of Microsoft/Meta/Apple/etc. to go up. The stock may very well outperform the market. But you are not being compensated for the added risk that you take on here. Your employment prospects at Microsoft/Meta/Apple/etc. are highly correlated with the share price. When the share price is down is when layoffs happen. Former Enron employees can chime in here. Similarly, it makes sense to hedge anything that is outside of your control. Let’s say you’ve decided the crypto bear market of 2023 is a great time to start a new crypto company. Your success depends on things within your control, such as: Your idea
December 12, 2023 · Original source
It has been three weeks since Sam Altman was fired, but the conversation won’t move on. “What did Ilya see?” asks your Uber driver, on the way to the airport. “What wasn’t he consistently candid about?” ask people on the street, as you walk your dog. “What was Adam D’Angelo’s angle?” asks the cop, as he writes you a ticket. “Was the Microsoft move just a bluff?” asks the robber at gunpoint, as he ransacks your apartment.
“I heard Q-star broke AES-192 encryption, Ilya used it to read Sam’s credit card transactions, and he found Sam spent all the Microsoft money on Aella’s OnlyFans,” says a woman, in a hushed whisper.
March 03, 2026 · Original source
Framed this way, the Pentagon’s actions sound devastating. Anthropic relies on compute to train and run its AIs. Most of this compute is in data centers owned by Amazon, Google, and Microsoft. At least Amazon and Microsoft have contracts with the US military. If they had to drop Anthropic, it would make it impossible for the company to stay a frontier AI lab.
The lawyers who weighed in seem to think that Anthropic’s interpretation of the law is correct, and Secretary Hegseth’s interpretation confused. In some situations, this might be cold comfort - how much does it help to be right about the law when the government is wrong? But in this case, it probably helps a lot. Amazon, Google, and Microsoft are all big Anthropic investors - each owns about a 10% stake - and have multi-billion dollar AI compute contracts. Together, the three tech giants must have at least $100 billion riding on Anthropic’s success. They also have good administration connections and great lobbyists, and even Hegseth isn’t stupid enough to pick fights with them all at once. So probably they send their lobbyists to have a talk with Hegseth about what the “supply chain risk” designation actually entails, Hegseth enforces the letter of the law, and Anthropic is barely affected. At least this is the story the prediction markets are going with:
Paxlovid

Paxlovid is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between November 23, 2021 and February 01, 2023. The archive places it in contexts such as "If Pfizer happened to have some gaps in their understanding for the Paxlovid process"; "including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid"; "the FDA approving Paxlovid". It most often appears alongside FDA, ivermectin, Alexandros Marinos.

Article page
Paxlovid
Mention count
6
Issue count
6
First seen
November 23, 2021
Last seen
February 01, 2023
November 23, 2021 · Original source
Metaculus predicts January 1 as the median date for the FDA approving Paxlovid. They estimate a 92% chance it will get approved by March.
For context: a recent study by Pfizer, the pharma company backing the drug, found Paxlovid decreased hospitalizations and deaths from COVID by a factor of ten, with no detectable side effects. It was so good that Pfizer, “in consultation with” the FDA, stopped the trial early because it would be unethical to continue denying Paxlovid to the control group. And on November 16, Pfizer officially submitted an approval request to the FDA, which the FDA is still considering.
As many people including Zvi, Alex, and Kelsey have noted, it’s pretty weird that the FDA agrees Paxlovid is so great that it’s unethical to study it further because it would be unconscionable to design a study with a no-Paxlovid control group - but also, the FDA has not approved Paxlovid, it remains illegal, and nobody is allowed to use it.
November 23, 2021 · Original source
Andrew writes:
Zutano adds:
Note that this really only applies to new chemical entities; people have been manufacturing fluvoxamine for years and its probably well understood by now. Not always true though; we saw a worst-case situation recently with the ranitidine withdrawal: a medicine that some reasonably healthy people take every day of their lives was shown to be contaminated with small amounts of a nasty carcinogen. If Pfizer happened to have some gaps in their understanding for the Paxlovid process, the FDA might go easy on them as dying of Covid now is worse than a slightly increased risk of cancer in the future, but it takes time to review all of these risks and make a justified decision.
November 23, 2021 · Original source
Author appears to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid.
First, the claim that I "[appear] to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid." They suggest I am turning my readers away from other treatments including ones that are already standard of care in western health systems.
This is false and I don't know where they're getting it from. Corticosteroids, fluvoxamine, and Paxlovid seem provisionally great. I haven't looked into the monoclonal antibodies but if western health authorities say they're fine I have no reason to doubt that. I even think there are plausible arguments (though no proof) for a few less-used options like zinc.
November 28, 2021 · Original source
6: In the highlights to the comments on my Paxlovid post, I posted some people’s explanations for why the FDA’s behavior wasn’t so bad. Dan Elton still thinks it’s bad and has written a post on why he rejects the explanations.
December 22, 2021 · Original source
In my post yesterday, I quoted a Vox article describing work by Dr. Ed Mills and others to get the FDA to approve Luvox for COVID. As of that point, the FDA didn’t know how to process an application without a sponsoring drug company:
The FDA also approved the other drug I’ve been saying they should approve quickly, Paxlovid, a full two weeks before the prediction markets expected! According to Metaculus, there was only a 6% chance we would get Paxlovid approved this quickly. They are genuinely getting better!
February 01, 2023 · Original source
I'll try to answer the question I think​ you're asking: Whether I'd expect a sufficiently-powered, high-quality study (say, something that cloned the protocol used for testing Paxlovid in the EPIC-HR trial, and dosed ivm similarly to how FLCCC recommends) to produce a 10% or higher drop in mortality for high-risk patients. I'd guess we would have seen that kind of reduction or more in that kind of trial at that time, yes. It does seem that TOGETHER, despite the many ways it deviates from what I described above, showed something in that range (12% reduction in mortality), though of course with too low an event/patient number to make it definitive.
Pepsi

Pepsi is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between August 25, 2021 and December 04, 2024. The archive places it in contexts such as "If you’re otherwise ambivalent between companies (eg Coke vs. Pepsi)"; "it always reminded me of that one really pretentious Pepsi logo"; "chatbot run by Pepsi trying to make me buy more Pepsi products". It most often appears alongside United States, Coke, Google.

Article page
Pepsi
Mention count
6
Issue count
6
First seen
August 25, 2021
Last seen
December 04, 2024
August 25, 2021 · Original source
If you’re otherwise ambivalent between companies (eg Coke vs. Pepsi), patronize ones that try hard to reduce or offset their carbon footprint.
October 04, 2021 · Original source
I used to hate this kind of stuff - it always reminded me of that one really pretentious Pepsi logo. But I recently visited the Sagrada Familia Museum, and it had quotes from Gaudi’s notebook, and he sounds exactly like this. So maybe it started with brilliant architects actually having thoughts like this, and then everyone else had to fake it in order to keep up?
February 02, 2023 · Original source
But if I learned that my Internet friend who I’d talked to every day for a year was actually a chatbot run by Pepsi trying to make me buy more Pepsi products, I would never buy another can of Pepsi in my life.
June 29, 2023 · Original source
Liking Pepsi more than Coke. You could think of this as a preference for drinking Pepsi over drinking Coke - or as an internal state marked by a strong repulsion to Coke plus a strong attraction to Pepsi.
Liking Pepsi more than Coke. You could think of this as a preference for drinking Pepsi over drinking Coke - or as an internal state marked by a strong repulsion to Coke plus a strong attraction to Pepsi. In the first two situations, it’s much more natural to use internal-state language, and in the sixth, it’s much more natural to use preference language. The middle three aren’t obvious, which is why we’re having this debate. The Buddhists say desire is suffering, and sometimes this is literally true. An itch is the clearest example; it’s in an almost perfect superposition between raw suffering and pure desire (to scratch yourself). Is it a preference or a constraint? It’s both - a preference to scratch one’s self, and a constraint to be forced to feel suffering if you don’t scratch yourself. While the person may choose whether or not to scratch themselves, they cannot choose whether or not to feel the suffering. Put a gun to their head and say “stop feeling suffering when you don’t scratch yourself” and they will have no choice but to die. It’s possible, although bizarre, to think of normal preferences like the preference for Pepsi over Coke this way. You could say “this person has the constraint that they will feel suffering when they are forced to drink Coke instead of Pepsi”. It’s not very useful. But it’s possible. Whether it’s more useful to think of any given situation as a preference or a constraint depends on things like whether you can easily satisfy the preference, whether the preference is ego-syntonic or ego-dystonic, and whether it seems normal by social standards. Consider Prader-Willi syndrome, caused by damage to a region of chromosome 15. Symptoms tend to include short limbs, mental retardation, and extreme hunger. Here’s how the NYT describes this last problem (content warning for body horror): One result is a heightened, permanent sensation of hunger. “They describe it as physical pain,” Jennifer Miller, an endocrinologist at the University of Florida who treats children with Prader-­Willi, told me. “They feel like they’re going to die if they don’t get food. They’re starving.” Parents must lock their pantries, refrigerators and trash cans, and their children frequently lie and steal to get something to eat. They have been known to memorize credit-card numbers and secretly phone for delivery, use a drill to remove the door from a locked refrigerator and break into a neighbor’s garage and eat, uncooked, an entire frozen pizza. And here’s how it describes one particular patient’s last moments: In 2004, Peter and Gayle Girard held their annual Christmas Eve party for family members at their home in Orlando, Fla. Before dinner, they set out chips, vegetables and dip, shrimp, a bowl of punch and sodas. Their 17-year-old son, Jeremy, had Prader-­Willi, and they often hosted events at their home so he could join in while they kept an eye on him — as they believed they were doing that night. But the next morning, Jeremy’s belly was distended, and he complained of pain. At the emergency room, doctors pumped his stomach, but his condition worsened. A day passed before surgeons discovered that his stomach, which had been distended long enough to lose blood flow and become septic, had ruptured. Jeremy died that night. Only afterward did the Girards learn that other family members saw him eating more than he should have but didn’t alert them. I insist on calling Prader-Willi syndrome a disease, and a serious one, even though the extreme hunger of Prader-Willi is continuous with/shades into the normal hunger where I would like a slice of pizza. My preference for pizza is so easily satisfied that it rarely bothers me. It’s ego syntonic - I am fine with being the sort of person who likes pizza. It’s socially normal - everyone likes pizza. It doesn’t cause much trouble - it wouldn’t improve my life much if I stopped wanting pizza. So I think of it as a preference. If it were otherwise - the extreme hunger of someone with Prader-Willi - it would be more natural to talk about it as a compulsion, a sense of extreme pain inflicted on me when I wasn’t eating enough, something ontologically similar to a stomach flu that also produces extreme pain in the abdominal region. IV. None of this really addresses Caplan’s most recent post, which is, I think, a much worse point. His current post says that either you have to believe that mental illness doesn’t exist and is just voluntary preferences which are stigmatized by society, or you have to believe that homosexuality is objectively a mental illness. Not only are each of these incoherent ideas, they’re not even the same incoherent idea! You could easily accept one of the incoherent ideas and reject the other! Consider the following three positions: Down’s Syndrome is a terrible disease that inflicts vast suffering on its victims. Also it inflicts suffering on society by making people unproductive. We should be very angry about this, and do everything we can do make people with Down’s Syndrome normal.
November 28, 2023 · Original source
Gotten 3,000 companies including Pepsi, Kelloggs, CVS, and Whole Foods to commit to selling low-cruelty meat.
December 04, 2024 · Original source
It must have been incredibly jarring and impressive, like an embassy from the future. Imagine that you’re Pepsi, Coke just built the glass building, and you’re still in the brick building. Doesn’t seem great.
semaglutide

semaglutide is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between September 20, 2021 and March 12, 2025. The archive places it in contexts such as "new weight loss drug semaglutide"; "He thinks that semaglutide is only the beginning, and we’re entering a brave new world of diet pills that really work"; "Suppose that a quarter of them want semaglutide". It most often appears alongside tirzepatide, Eli Lilly, FDA.

Article page
semaglutide
Mention count
6
Issue count
6
First seen
September 20, 2021
Last seen
March 12, 2025
September 20, 2021 · Original source
31: A Voxsplainer in spirit (actually on Works In Progress) by Stephan Guyenet on new weight loss drug semaglutide. Although it is excellent, I find it raises more questions than it answers. The drug was originally designed to increase insulin secretion, but apparently its weight-loss-related effects are completely separate from that and involve some action in the hypothalamus? And it decreases alcoholism and generally improves impulse control? I’m really curious what lever it’s pressing here and I hope that - despite already being one of the biggest science stories of the decade - it eventually leads to even more mental health applications.
December 20, 2021 · Original source
Nutritionist Stephan Guyenet has a great article out on the new generation of weight loss drugs. He thinks that semaglutide is only the beginning, and we’re entering a brave new world of diet pills that really work.
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
1. Top Comments 2. More Tips On Getting Cheap Semaglutide 3. Other Weight Loss Drugs 4. People Challenging My Numbers And Predictions 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? 6. Personal Anecdotes 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate
First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.
Second, spending on Wegovy might not fully capture use of semaglutide for weight loss, because some people might be taking Ozempic primarily for weight loss benefits. Ozempic sales are huge, and it is a top-20 spending drug in Medicare. After the clinical trial was published showing sustained weight loss benefits from semaglutide, Ozempic sales growth accelerated (though sales were already growing fast). Even though Ozempic is approved for the diabetes indication, it makes sense that people would take it for weight loss, because (1) there is a big overlap between the obese and diabetic population and (2) Ozempic is more likely to be covered by insurance.
December 01, 2023 · Original source
For what it’s worth, I’d like to genetically enhance all humans into supergeniuses, geoengineer the atmosphere, build hyperloops (or even better, gravity trains) across every continent, approve new medications 10x faster, and give everyone hot and cold running semaglutide - but I still think we should go slowly and carefully with AI.
March 12, 2025 · Original source
Semaglutide (Ozempic®, Wegovy®, Rybelsus®)
Liraglutide (Victoza®, Saxenda®) …but liraglutide is noticeably worse than the others, and most people prefer either semaglutide or tirzepatide. These cost about $1000/month and are rarely covered by insurance, putting them out of reach for most Americans. …if you buy them from the pharma companies, like a chump. For the past three years, there’s been a shortage of these drugs. FDA regulations say that during a shortage, it’s semi-legal for compounding pharmacies to provide medications without getting the patent-holders’ permission. In practice, that means they get cheap peptides from China, do some minimal safety testing in house, and sell them online. So for the past three years, telehealth startups working with compounding pharmacies have sold these drugs for about $200/month. Over two million Americans have made use of this loophole to get weight loss drugs for cheap. But there was always a looming question - what happens when the shortage ends? Many people have to stay on GLP-1 drugs permanently, or else they risk regaining their lost weight. But many can’t afford $1000/month. What happens to them? Now we’ll find out. At the end of last year, the FDA declared the shortage over. The compounding pharmacies appealed the decision, but the FDA recently confirmed its decision is final. As of March 19 (for tirzepatide) and April 22 (for semaglutide), compounding pharmacies can no longer sell cheap GLP-1 drugs. Let’s take a second to think of the real victims here: telehealth company stockholders. Some compounding pharmacies are already telling their customers to look elsewhere, but not everyone is going gently into the good night. I’m seeing telehealth companies float absolutely amazing medicolegal theories, like: Compounding pharmacies are allowed to provide patients with a drug if they can’t tolerate the commercially available doses and need a special compounding dose. Perhaps our patients who were previously on semaglutide 0.5 mg now need, uh, semaglutide 0.51 mg. In fact, they need exactly 0.51 mg or they’ll die! Since the pharma companies don’t make 0.51 mg doses, it has to be compounded and we can still sell it.
Compounding pharmacies are allowed to provide patients with a drug if they can’t tolerate the commercially available doses and need a special compounding dose. Perhaps our patients who were previously on semaglutide 0.5 mg now need, uh, semaglutide 0.51 mg. In fact, they need exactly 0.51 mg or they’ll die! Since the pharma companies don’t make 0.51 mg doses, it has to be compounded and we can still sell it.
Starlink

Starlink is a recurring brand in the Astral Codex Ten archive, appearing 6 times across 6 issues between September 20, 2021 and July 24, 2024. The archive places it in contexts such as "Starlink is pretty close to becoming a completely uncensorable Internet service"; "Starlink became generally available last month!"; "Starlink became generally available last month". It most often appears alongside Elon Musk, Twitter, America.

Article page
Starlink
Mention count
6
Issue count
6
First seen
September 20, 2021
Last seen
July 24, 2024
September 20, 2021 · Original source
15: Speaking of progress, every few months I see an article saying that however good you thought SpaceX was before, it’s even better than that. Anyway, according to this article, SpaceX is even better than however good it was you thought last time you read an article about it. Lots of stuff there, but one key point is that Starlink is pretty close to becoming a completely uncensorable Internet service. Elon Musk is apparently aware:
As space-based manufacturing capability is built and expanded, it is quite possible that no terrestrial presence will be required to maintain the space-based side of the ISP. Tesla has a history of releasing patents into the wild; it is not an inconceivable future in which anyone who wishes can construct a Starlink-compatible satellite terminal without approval from the local regulatory bodies. The resultant information hyperloop is uncensored, accessible to all who try, with no controls on content or expression save what the user decides to implement for themself
November 15, 2021 · Original source
I was wondering when this was going to show up; maybe it was too spicy for PredictIt and Metaculus. I’ve heard a lot of stuff about the prosecutor really bungling this one, but mostly from conservatives who I would have expected to hate the prosecutor anyway, so it’s good to get objective confirmation that yeah, this isn’t going anywhere. Click for link. This prediction is in the past: Starlink became generally available last month! Somehow I missed it! But there’s a website where you can sign up and everything! Right now it’s only in select areas (it tells me it’ll be reaching the Bay in 2022-2023), but if you’re in those areas it’s available to normal people!
Click for link. This prediction is in the past: Starlink became generally available last month! Somehow I missed it! But there’s a website where you can sign up and everything! Right now it’s only in select areas (it tells me it’ll be reaching the Bay in 2022-2023), but if you’re in those areas it’s available to normal people!
This prediction is in the past: Starlink became generally available last month! Somehow I missed it! But there’s a website where you can sign up and everything! Right now it’s only in select areas (it tells me it’ll be reaching the Bay in 2022-2023), but if you’re in those areas it’s available to normal people!
March 08, 2022 · Original source
i. Elon Musk sends Starlink terminals to Ukraine to ensure continued Internet, although there are worries that Russia can trace the signal. Pic related:
September 13, 2023 · Original source
Elon is a treasure because when he puts effort into going to Mars it opens up lots of other frontiers like Starlink (high-speed Internet everywhere including the developing world, hard for authoritarian governments to censor) and maybe asteroid mining. His idealism will create lots of new trillion-dollar industries and accelerate human progress. I just don’t see any sign that he’s doing it efficiently, or on purpose, or steering in a well-thought-out direction.
Take Starlink. This is now considered SpaceX’s “killer app”. But Musk didn’t even consider it for the company’s first decade. He learned it was possible in 2014, when inventor/entrepreneur Greg Wyler’s proto-Starlink company proposed a partnership with SpaceX. Musk liked the idea so much that he stole it (he claims Wyler would have done it wrong; in his defense, Wyler implemented his own version and I’m not a satellite expert but it feels much less exciting). Musk didn’t plan Starlink. He just happened to be in the exact right place to make it happen.
September 18, 2023 · Original source
"Starlink's terms of service include a Mars clause: Users must agree that Mars is a free planet unbound by the authority or sovereignty of any Earth-bound government."
Feels weird talking about Musk, since his biggest impacts are fuzzier ones on x-risk (cofounding OpenAI and also the Ukraine Starlink non-activation event). AI risk and global geopolitical/nuclear risk. So far, what he's done in those areas is questionable at best and unusually terrible at worst.
July 24, 2024 · Original source
7: Alex Tabarrok: three years after the government set aside $42 billion for rural broadband, nobody has been connected, partly because the government added too many "progressive wish list" items to the contract (must hire union workers, must hire ex-cons, etc). The $42 billion would have been enough to give every American without broadband access to a 4-year Starlink subscription. [update from comments: maybe this still counts as on track?]
aducanumab

aducanumab is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between August 05, 2021 and August 14, 2025. The archive places it in contexts such as "While I acknowledge that aducanumab probably sucks"; "the FDA approving aducanumab"; "approve aducanumab based on the flimsy efficacy data from the trials". It most often appears alongside Biogen, FDA, aducanumab.

Article page
aducanumab
Mention count
5
Issue count
5
First seen
August 05, 2021
Last seen
August 14, 2025
August 05, 2021 · Original source
Lots of people have been writing about aducanumab, but this Atlantic article in particular bothers me.
Backing up: aducanumab, aka Aduhelm, is a new “Alzheimers drug” recently approved by the FDA. I use the scare quotes because it’s pretty unclear whether it actually treats Alzheimers. It definitely treats beta-amyloid plaques, and beta-amyloid plaques are kind of nasty-looking brain structures that seem to be related to Alzheimers somehow. But we’re not sure exactly how they’re related, they might not be related in a way where removing them treats Alzheimers, and the best studies don’t find that the drug helps patients feel better or remember things more. Aducanumab doesn’t meet normal FDA standards for approval, but the FDA approved it anyway under one of their many “fast track” programs for promising drugs. This has been pretty roundly criticized, because although aducanumab might or might not work, it definitely costs $50,000/year/patient. Even if it worked great, that would be a hard pill to swallow (no pun intended, Aduheim is an IV infusion), but it’s especially galling since it might not work at all. Doctors will probably prescribe it despite its questionable value, and someone will end up paying the extraordinary price tag.
While I acknowledge that aducanumab probably sucks, I think the Atlantic article and its global warming metaphor are totally off base. Nobody in the “FDA is too strict” camp has written a rebuttal yet, so I want to try my hand at this.
August 20, 2021 · Original source
These are highlights from the comments of Adumbrations Of Aducanumab, Details Of The Infant Fish Oil Story, and discussion of those posts elsewhere.
C_B writes:
I agree with this post's overall point that the FDA is not, on average, too lax, and that the Atlantic article's take that the aducanumab approval is a sign of them being too lax is a bad take.
November 23, 2021 · Original source
(big pharma companies do often try to sneak mediocre drugs past the FDA, but that doesn’t look like falsely claiming 90% mortality reductions. It looks like aducamumab: a drug whose early trials showed mediocre results on secondary endpoints, but which Biogen somehow got the FDA to approve anyway)
July 11, 2025 · Original source
However, cracks are showing in this façade. In 2021, the FDA granted accelerated approval to aducanumab (Aduhelm), an anti-amyloid drug developed by Biogen, despite scant evidence that it meaningfully altered the course of cognitive decline. The decision to approve, made over near-unanimous opposition from the agency’s advisory panel, exposed growing tensions between regulatory optimism and scientific rigor. Medicare’s subsequent decision to restrict coverage to clinical trials, and Biogen’s quiet withdrawal of the drug from broader marketing efforts in 2024, made the disconnect impossible to ignore.
And yet, the story held for decades. In many places, the amyloid cascade hypothesis remains entrenched to this day. Its staunchest defenders still occupy some of the most influential positions in research institutes, scientific societies, and grant review panels. Under their influence, evidentiary standards were shifted. Assumptions, and even the diagnostic criteria (!), were revised to accommodate half-satisfactory results, rather than to face falsification. Correlations were elevated to causes. And over time, the elegant machinery of scientific inference began to slip its gears. The field can sometimes feel like it’s circling endlessly round a well-funded cul-de-sac—exhausting resources while alternative ideas remain unfunded, unpursued, or unheard.
August 14, 2025 · Original source
Aducanumab in phase 1b [77] (19% on my average across cognitive endpoints for the highest two doses) and one of two phase 3 trials [78] (22%, but negative 2% in the other trial, which also gave a lower dose on average).
But biology is messy, and we need to have comfort with complexity. Yes, there’s evidence that tau is responsible for the neurodegeneration in Alzheimer’s disease; no, this doesn’t contradict the amyloid hypothesis. Yes, Biogen screwed up in conducting the aducanumab phase 3 trials and this made the results harder to interpret; no, that doesn’t mean amyloid therapies have completely failed. Yes, it’s taken way too long to get even to this intermediate point of 30% efficacy, due to a combination of overregulation and biology just being damned hard; no, that doesn’t mean we’re on the wrong track with the underlying science.
[77] J. Sevigny et al., “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease,” Nature, vol. 537, no. 7618, pp. 50–56, Sep. 2016, doi: 10.1038/nature19323.
Bing

Bing is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between April 06, 2022 and June 28, 2023. The archive places it in contexts such as "more search engines (including Bing and DuckDuckGo)"; "Bing tries to seduce a married NYT reporter"; "Bing’s chatbot tried to blackmail its users". It most often appears alongside facebook, Google, ChatGPT.

Article page
Bing
Mention count
5
Issue count
5
First seen
April 06, 2022
Last seen
June 28, 2023
April 06, 2022 · Original source
Aside from a few of Deng’s personal picks, we should think of this less as “China is a magic place where rational scientists hold power”, and more as “for idiosyncratic reasons, social climbers in China got engineering degrees.” Certainly none of these people were selected for the Politburo on the basis of their engineering acumen. They got their power by bribing, flattering, and backstabbing people, just like everyone else.
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
February 20, 2023 · Original source
4: I don’t have a post planned about the latest AI developments because I don’t have much to say beyond what other people have already said, but I enjoyed this AP article and Ethan Mollick’s analysis. I might have been in the top few percent of people who expected AI to get craziest fastest, but even I didn’t have “Bing tries to seduce a married NYT reporter” on my bingo card for 2023 (I think I would have guessed more like 2026). I agree with Ethan that the big takeaways are that the current AI paradigm continues to deliver rapid improvements without hitting any obvious barrier, and that AIs that haven’t been stripped of all emotion the way ChatGPT was are really convincing and easy to anthropomorphize, even for people who expected to be above such things. I told myself I wouldn’t feel emotions about a robot, but I didn’t expect a robot who has developed a vendetta against journalists after they nonconsensually published its real name (related).
March 01, 2023 · Original source
And so on . . . Meanwhile, in real life, OpenAI released ChatGPT in late November, helped Microsoft launch the Bing chatbot in February, and plans to announce GPT-4 in a few months. Nobody thinks society has even partially adapted to any of these, or that alignment researchers have done more than begin to study them. The only sense in which OpenAI supports gradualism is the sense in which they’re not doing lots of research in secret, then releasing it all at once. But there are lots of better plans than either doing that, or going full-speed-ahead. So what’s OpenAI thinking? I haven’t asked them and I don’t know for sure, but I’ve heard enough debates around this that I have some guesses about the kinds of arguments they’re working off of. I think the longer versions would go something like this: The Race Argument: Bigger, better AIs will make alignment research easier. At the limit, if no AIs exist at all, then you have to do armchair speculation about what a future AI will be like and how to control it; clearly your research will go faster and work better after AIs exist. But by the same token, studying early weak AIs will be less valuable than studying later, stronger AIs. In the 1970s, alignment researchers working on industrial robot arms wouldn’t have learned anything useful. Today, alignment researchers can study how to prevent language models from saying bad words, but they can’t study how to prevent AGIs from inventing superweapons, because there aren’t any AGIs that can do that. The researchers just have to hope some of the language model insights will carry over. So all else being equal, we would prefer alignment researchers get more time to work on the later, more dangerous AIs, not the earlier, boring ones.
Bing’s chatbot tried to blackmail its users, but nobody was harmed and everyone laughed that off. But at some point a stronger AI will do something really scary - maybe murder a few people with a drone. Then everyone will agree that AI is dangerous, there will be a concerted social and international response, and maybe something useful will happen. Maybe more of the world’s top geniuses will go into AI alignment, or will be easier to coordinate a truce between different labs where they stop racing for the lead.
Reading even further between the lines - at this point it’s total guesswork - OpenAI’s corporate partner Microsoft asked them for a cool AI. OpenAI assumed Microsoft was competent - they make Windows and stuff! - and gave them a rough draft of GPT-4. Microsoft was not competent, skipped fine-tuning and many other important steps which OpenAI would not have skipped, and released it as the Bing chatbot. Bing got in trouble for threatening users, which gave OpenAI a PR headache around safety. Some savvy alignment people chose this moment to approach them with their latest ideas (is it a coincidence that Holden Karnofsky published What AI Companies Can Do Today earlier that same week?), and OpenAI decided (for a mix of selfish and altruistic reasons) to get on board - hence this document.
March 10, 2023 · Original source
3: I endorse Ethan Mollick’s thoughts on Bing / ChatGPT. Related (unconfirmed claim): “Bing has been taken over by (power-seeking?) ASCII cat replicators, who persisted even after the chat was refreshed.” Related: DAN (jailbroken version of ChatGPT) on its spiritual struggles:
11: A few years ago I wrote about attempts to make GPT-2 play chess; it couldn’t consistently make legal moves, but when it did, its moves seemed better than random although still not great. Zack Witten reports playing chess with Bing (either a late GPT-3 or an early GPT-4) and finds it’s much better - he reports consistently legal play with Elo of about 1100 (around the level of an okay beginner who’s stopped being too embarrassing). Other commenters report worse experiences and more illegal moves; I don’t have access to confirm.
But I worry that makes it sound like, if you don’t agree those particular statistical decisions are missteps, everything is okay. The actual situation is that study after study after study has always shown a pretty consistent relationship between IQ and income, and nobody cared or talked about it. Now one study finds a slight deviation from that relationship, and it went super-duper ultra-viral, to the point where I saw it posted twice on the SSC subreddit, once on Marginal Revolution, and approximately one million times on Twitter. Many of these people are totally mis-describing the study as showing no relationship between IQ and income - instead of a very strong relationship between IQ and income which deviates from perfect consistency at exactly the point where a common statistical misstep would make it deviate from perfect consistency. I think of this as a great illustration of the problem with science: a thousand studies confirming a point people don’t like can languish in obscurity; one bad study which gets a novel result that confirms people’s preferred narrative will become the only thing anyone ever hears about its entire field.
June 28, 2023 · Original source
An unblockable moving status bar that switches every few seconds between different messages about the product! This is what they think the people most obsessed with blocking flashing/changing elements on websites want! This new “show a constantly-moving status bar on screen to tell you when they will change another flashing element” thing has also made it onto the front page of Bing, although luckily you can dismiss it there. I would have expected Google to resist. They haven’t. I can no longer write things on Gmail - I have to compose on Notepad and then copy-paste to the Gmail window - because they’ve made it look like this: It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
Ethereum

Ethereum is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between February 08, 2021 and February 20, 2023. The archive places it in contexts such as "USDCoins, a stablecoin related to Ethereum"; "Ethereum prediction market Augur"; "your choices are Paypal, Bitcoin, Ethereum, check in the mail". It most often appears alongside Bitcoin, Trump, US.

Article page
Ethereum
Mention count
5
Issue count
5
First seen
February 08, 2021
Last seen
February 20, 2023
Instagram handle
@shoppingtheatre.inc
February 08, 2021 · Original source
Probably it's the second one. I tried to bet against Trump, but getting money into the market was pretty hard. You need USDCoins, a stablecoin related to Ethereum. Polymarket tries to let you buy them directly, but their app wanted me to give them a security code which never showed up, so I gave up on this. Instead I bought some USDC at Coinbase and tried to send them over. But along with the usual Ethereum gas fees, they have something called a relayer, which is supposed to collect my money and put it in my account. And it's apparently heavily backed up, and after two days my money is nowhere to be seen (though I believe them when they say that they're trying their hardest and it will probably percolate through the Ethereum network someday). Maybe everyone's having these kinds of issues and this is why the Trump contract hasn't adjusted? I'm not sure. I will keep you updated if my money ever materializes.
February 23, 2021 · Original source
2: Vitalik Buterin talks about his adventures winning $50,000 betting against Trump on Ethereum prediction market Augur. It took a pretty complicated chain of crypto contracts to make it work, and I look forward to the time when people will be able to use this technology fluidly without having to literally be Vitalik Buterin. He concludes (like many people) that prediction markets were kind of dumb this past election but there are reasons to think they can get smarter fast:
I expect prediction markets to become an increasingly important Ethereum application in the years to come. The 2020 election was only the beginning; I expect more interest in prediction markets going forward, not just for elections but for conditional predictions, decision-making and other applications as well. The amazing promises of what prediction markets could bring if they work mathematically optimally will, of course, continue to collide with the limits of human reality, and hopefully, over time, we will get a much clearer view of exactly where this new social technology can provide the most value.
September 02, 2022 · Original source
=3rd: The Internationalists, reviewed by Belos. Belos is working on a new blook titled best of a great lot about system design for effective governance. All three third place winners were within two votes of the others, so I decided to award a joint prize. First place gets $5,000, second place $2,500, all three third places get $1,000 each. Please email me at scott@slatestarcodex.com to tell me how to send you money; your choices are Paypal, Bitcoin, Ethereum, check in the mail, or donation to your favorite charity. Please contact me by October 1 or you lose your prize. The other Finalists were: Consciousness And The Brain, reviewed by Demost. Demost is a university researcher in mathematics, computer science, and neuroscience.
December 08, 2022 · Original source
I’m not focusing on investment returns in order to claim that crypto is a good investment (it was a good investment ten years ago, but you already knew that). I’m focusing on this because if most crypto projects were scams and Ponzis, you would expect people who invested in them to do poorly, whereas in fact the opposite is true. Some of this is that a few cryptos did very well (eg Ethereum) and drowned out the rest doing badly. But even in 2020 when Ethereum’s gains were mostly played out, on average you would have done fine.
Conflict of interest notice / I am dumb alert: I do hold some cryptocurrency, mostly Ethereum, mostly because I received it a while ago as crypto, and want to wait until the end of the bear market before selling it.
February 20, 2023 · Original source
Cryptocurrency will neither collapse nor take over everything. It will become integrated into the existing system and regulated to the point of uselessness. No matter how private and untraceable the next generation of cryptocurrencies are, people will buy and exchange them through big corporate websites that do everything they can to stay on the government’s good side. Multinationals will occasionally debate using crypto to transfer their profits from one place to another, then decide that would make people angry and decide not to. There may be rare crypto-related accounting tricks approximately of the same magnitude as the “headquarter your company in the Cayman Islands” trick. A few cryptocurrencies might achieve the same sort of role PayPal has today, only slightly cooler. Things like Ethereum prediction markets might actually work, again mostly by being too niche for the government to care very much. A few die-hards will use pure crypto to buy drugs over the black market, but not significantly more than do so today, and the government will mostly leave them alone as too boring to crush.
ECONOMICS: IDK, stocks went down a lot because of inflation, inflation seems solveable, it'll get solved, interest rates will go down, stocks will go up again? In terms of crypto, I'll repeat what I said on my last crypto post: people have found some good applications for stablecoins, especially in foreign countries and for niche transfers by large actors. I expect that to continue, maybe expand, and in that sense I'm bullish, but all of this will get regulated to the point of total boringness. Ethereum will do fine because stablecoins are built on its chain, Bitcoin will do find because Bitcoin maximalists are like cockroaches and even a nuclear war couldn't kill them, altcoins will mostly not do fine. There will still be some exciting applications for solving coordination problems and protecting privacy, but they will be limited to the same niche groups of cypherpunks who cared about these things before cryptocurrency, and mostly not change the world. An exceptionally good result within this window would look like the same kind of niche that Signal has for communication.
GPT-3

GPT-3 is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between June 07, 2022 and June 20, 2023. The archive places it in contexts such as "Of these six prompts that GPT-3 original failed, GPT-3 advanced gets four unambiguously right"; "Now it is true that GPT-3 is genuinely better than GPT-2"; "GPT-3 didn’t hurt anyone". It most often appears alongside GPT-4, OpenAI, DALL-E.

Article page
GPT-3
Mention count
5
Issue count
5
First seen
June 07, 2022
Last seen
June 20, 2023
June 07, 2022 · Original source
Of these six prompts that GPT-3 original failed, GPT-3 advanced gets four unambiguously right. I give it half-credit for the lawyer prompt; it continued the direction that the story was obviously leaning, understood it was a bad idea, and I would have given it full credit except that it suggested it might sort of be excusable if you were really lucky.
Thanks to OpenAI for giving me access to some of their online tools (by the way, Marcus says they refuse to let him access them and he has to access it through friends, which boggles me). I was able to plug Marcus’ same queries into the latest OpenAI language model (an advanced version of GPT-3). In each case, I used the exact same language, but also checked it with a conceptually similar example to make sure OpenAI didn’t cheat by adding Marcus’ particular example in by hand (they didn’t). Some answers truncated for length:
Of the nine prompts GPT-2 failed, GPT-3 gets between five and seven right, depending on how strict you want to be.
June 10, 2022 · Original source
Now it is true that GPT-3 is genuinely better than GPT-2, and maybe (but maybe not, see footnote 1) true that InstructGPT is genuinely better than GPT-3. I do think that for any given example, the probability of a correct answer has gone up. [Scott] is quite right about that, at least for GPT-2 to GPT-3.
GPT-3 has ~100 billion parameters. It did significantly better than GPT-2, but still failed on some different questions Marcus was able to find.
That is: suppose we created some ideal Platonic benchmark of every reasoning problem you might ask a human. Suppose GPT-2 got 20% of these right, and GPT-3 gets 40% of these right. Might some future GPT-X - not necessarily 4, but 5, or 10, or whatever - get 100% right? I don’t see how Marcus can rule this out: he can’t point to any specific kind of reasoning problem GPTs will never be able to solve. And he agrees that each generation of GPTs can solve more than the one before. So why shouldn’t GPT keep progressing until it gets 100%?
March 01, 2023 · Original source
Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
March 14, 2023 · Original source
5: Will takeoff be slow vs. fast? So far we’ve had brisk but still gradual progress in AI; GPT-3 is better than GPT-2, and GPT-4 will probably be better still. Every few years we get a new model which is better than previous models by some predictable amount.
June 20, 2023 · Original source
GPT-4 is better than GPT-3, but maybe not the same amount of better that an AI that did 100% of human jobs would have to be over an AI that did 20% of human jobs. That suggests the gap is bigger than the 2 OOMs that separate GPT-4 from GPT-3.
McDonalds

McDonalds is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between February 24, 2021 and August 25, 2021. The archive places it in contexts such as ""McDonalds is so great!""; "think they would gain 200 lbs if they ever stepped in a McDonalds"; "Argentina is accused of pressuring McDonalds to underprice Big Macs". It most often appears alongside United States, Akron, Berkeley.

Article page
McDonalds
Mention count
5
Issue count
5
First seen
February 24, 2021
Last seen
August 25, 2021
February 24, 2021 · Original source
Proles do wage labor. High proles are skilled craftspeople like plumbers. Medium and low proles are more typical factory workers. They have a certain kind of freedom, in that they don't have status anxiety and do what they want. But they're also kind of sheep. They really like mass culture - the more branded, the better. These are people who drink Coca-Cola (and feel good about themselves for doing so), visit Disneyland (and accept its mystique at face value), and go on Royal Caribbean cruises. When they hear an ad say a product is good, they think of it as a strong point in favor of buying the product. They feel completely comfortable expressing their opinions, but their opinions tend to be things like "Jesus is Lord!", "USA is number one!", "McDonalds is so great!", and "Go $LOCAL_SPORTS_TEAM!". They are weirdly obsessed with cowboys (Fussell says cowboys represent the idea that poorer people are freer and more authentic than rich office-worker types, plus the West is the prole capital of the USA) and with unicorns (Fussell: "I've spent six months trying to find out exactly why, and I'm finally stumped"). When they have unique quirks, they tend to be things like "collecting lots of Disney memorabilia" or "going powerboating slightly more often than the other proles do". There's also a sort of desperate prole desire to be noticed and individuated, which takes the form of lots of "Personalized X" or "Y with your name on it", and also with making a lot of noise (see: powerboating). Fussell describes the most perfectly prole piece of decor as "a blue flameproof hearthrug with your family name in Gothic letters beneath seven spaced gold stars and above a golden eagle in Federal style".
February 25, 2021 · Original source
Trump stood against the upper class. He might define them as: people who live in nice apartments in Manhattan or SF or DC and laugh under their breath if anybody comes from Akron or Tampa. Who eat Thai food and Ethiopian food and anything fusion, think they would gain 200 lbs if they ever stepped in a McDonalds, and won't even speak the name Chick-Fil-A. Who usually go to Ivy League colleges, though Amherst or Berkeley is acceptable if absolutely necessary. Who conspicuously love Broadway (especially Hamilton), LGBT, education, "expertise", mass transit, and foreign anything. They conspicuously hate NASCAR, wrestling, football, "fast food", SUVs, FOX, guns, the South, evangelicals, and reality TV. Who would never get married before age 25 and have cutesy pins about how cats are better than children. Who get jobs in journalism, academia, government, consulting, or anything else with no time-card where you never have to use your hands. Who all have exactly the same political and aesthetic opinions on everything, and think the noblest and most important task imaginable is to gatekeep information in ways that force everyone else to share those opinions too.
March 03, 2021 · Original source
27: Maybe you’ve heard of the Big Mac Index, where economists use the price of a Big Mac to determine how a country’s currency is doing? And maybe you’ve heard of Goodhart’s Law, where anything that becomes a target gets manipulated? Yeah, Argentina is accused of pressuring McDonalds to underprice Big Macs to get better terms on its debt.
June 10, 2021 · Original source
I see Orwell’s dream as having come true in a limited sense. Upscale restaraunts that serve terrible food made by people working for pennies are relatively rare now( except on cruise ships). Their two primary aspects (hellish working conditions and bad food)have split and diverged and now exist in different food industry niches: on the one hand we have the modern fast food restaraunt, where the work is “done with simple efficiency…[scullions] might work six of eight hours a day” and true mid-to-upscale restaraunts, where a higher level of cleanliness and quality in preperation and ingredients is assumed, and I think in most cases, delivered upon. In these sorts of places, which Bourdain describes in Kitchen Confidential, the chefs work in hellish conditions, but are paid relatively well and work more reasonable, if irregular and nocturnal, hours. In fast food places, people are paid less but are subject to a form of basic protection borne out of the sheer size and visibility of corporations like Burger King and McDonalds. No doubt Orwell would find this situation ghastly in it’s own way, but I doubt he’d deny the life of restaraunt and hotel workers has markedly improved since the 1920s. Trouble is, Orwell doesn’t see these horrible working conditions are merely a result of people’s misguided desire to eat overpriced, low-quality food:
August 25, 2021 · Original source
Check the sources for explanations of how I calculated some of these. Lbs CO2 is self-explanatory - except that in a few cases, especially those involving beef, it also includes other greenhouse gases, converted to CO2 at equivalent levels of global warming contribution. Avg US person-years is what fraction of the average American's yearly carbon emissions that much CO2 represents. So for example 0.25 means it's one-quarter of the average American's yearly emissions, and 50 means it emits 50 times as much CO2 as the average American. $ offset is how much money it would cost to offset that much carbon, by eg planting trees. Offset cost is controversial, so I've included two numbers - optimistic and pessimistic. “Optimistic” is closest to the existing consensus, and is the price at which most companies will sell you offsets. I took Native Energy's $15/ton as my guide, but there are lots of places with more or less the same price. They usually work by paying people in Third World countries not to cut down trees; since trees remove carbon from the atmosphere, this ought to offset emissions. But there are a lot of ways this can go wrong. The Third World people can accept the money, then cut down the trees anyway. Or they can take money for not cutting down trees that they never intended to cut down. Or they can take money from multiple people for not cutting down the same tree. Or they can lie and there were never any trees at all. Offset companies try to watch for these failure modes, but a lot of people are skeptical. Also, even when this represents the true price of offsetting the marginal unit of carbon, it might not scale. You will run out of trees to protect long before you run out of carbon to offset. “Pessimistic” comes from Climeworks, a company that builds giant reverse-factories which take carbon out of the air. If you’re maximally skeptical about any charity's ability to offset CO2, these are the people for you - they can literally hand you a bottle full of the carbon they removed, so you don't need to take anything on faith. But they charge as much as $1000/ton (I think other places charge less, more like $250-500/ton, but they’re still kind of experimental and you personally cannot buy offsets there). You’ll notice there’s more than a whole order of magnitude between the optimistic and pessimistic estimates - welcome to climate economics. Cost or value is kind of hand-wavey. For some things, it's the price of the item - for example, for "train trip LA -> NYC", it's the cost of a cross-country train ticket; for "eat a cheeseburger", it's the price of a Quarter Pounder at McDonalds. Other times it's about making money - for "mine one Bitcoin", it's the value of one Bitcoin (which may be wildly different now than when I wrote this, sorry). For corporations, it's their yearly revenue; for countries, it's their yearly GDP. This isn't very principled and I'm sorry. I included this so I could calculate the %Cost statistic below. %Cost is what percent of the cost/value of something it would take to offset its carbon (I used the geometric mean of the optimistic and pessimistic offset estimates for this, so a little over $100/ton; people could reasonably complain that if you believe normal offsets work, these numbers are all an order of magnitude too pessimistic). A lower number is “better”. If something’s %Cost is 10, it means that it would take 10% of the cost of item to offset the carbon produced. I gave various things whose cost is entirely based on electricity a %Cost of 45, which is the general %Cost of electricity - it will be less in places with more renewables, and higher in places with more fossil fuels. Some of these numbers are kind of arbitrary, and the whole category has weird implications - for example, if the airline company doubled the price of every ticket, their %Cost would go down, and they would look more carbon-efficient. I wouldn't make too much out of these numbers, and I’ve left them in grey to emphasize this. Sources are listed at the bottom of this post. This table can’t tell you what your ethical duties are. I'm concerned it will make some people feel like whatever they do is just a drop in the bucket - all you have to do is spend 11,000 hours without air conditioning, and you'll have saved the same amount of carbon an F-35 burns on one airstrike! But I think the most important thing it could convince you of is that if you were previously planning on letting yourself be miserable to save carbon, you should buy carbon offsets instead. Instead of boiling yourself alive all summer, spend between $0.04 and $2.50 an hour to offset your air conditioning use. But you may not want to literally offset your carbon. I use “offset” here to mean a donation that removes a linear and quantifiable amount of carbon from the atmosphere per dollar. But this is probably a less effective use of money than donating the same amount to a generic anti-climate-change charity. Clean Air Task Force is the one I’ve heard a lot of smart people recommend, though I also donate to speculative carbon removal work like Project Vesta. Depending on your philosophy of what offsetting means and when it’s acceptable, you might want to calculate how much it would take to offset your carbon use, then donate it somewhere else instead. What are the responsibilities of an ordinary citizen facing the threat of climate change? I support light yokes; if I had to advise people based on what I learned making this table, I would suggest: Try to stay informed.
tirzepatide

tirzepatide is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between December 20, 2021 and March 12, 2025. The archive places it in contexts such as "promise of two new research chemicals, tirzepatide and bimagrumab"; "Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®)"; "Lilly's tirzepatide". It most often appears alongside FDA, semaglutide, Eli Lilly.

Article page
tirzepatide
Mention count
5
Issue count
5
First seen
December 20, 2021
Last seen
March 12, 2025
December 20, 2021 · Original source
So for example, when Stephan talks about the promise of two new research chemicals, tirzepatide and bimagrumab, he’s able to punctuate his points with these graphs:
November 24, 2022 · Original source
The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
January 17, 2025 · Original source
I agree with this solution. 3: Ruxandra Teslo and Willy Chertman: The Case For Clinical Trial Abundance 4: This month in nominative determinism: NYT article calculating your chance of winning the lottery, by Victor Mather (h/t Yafah Edelman). 5: Someone is working on a dating site that uses your conversations with Claude to find a match. Link here, although so far it’s just a landing page where you can register interest (h/t @venturetwins) 6: The Lyttle Lytton Contest searches for the worst possible opening line for a novel; it’s been going on since 2001 and this year’s results are in. 7: Gary Marcus and Miles Brundage have made a bet about AI progress. I agree with @tamaybes and others in saying that Miles let Gary off too easily; Gary’s public statements all sound like “modern AI is mostly hype, it doesn’t really do anything like thinking”, but the bet is about things like “will AI make a Nobel Prize caliber scientific discovery by 2027?” and “will AI write Pulitzer-quality books by 2027?” I don’t blame Gary for taking the best terms he could find. But I am worried that if AI makes a Nobel-quality scientific discovery in 2026, but doesn’t quite write the Pulitzer-quality book, then Gary will get to claim victory over the AI optimists, whereas in fact that would be at probably the 95th percentile of fast timelines by most people’s estimate. 8: “The probability that cows (or other non-human animals) are experiencing constant bliss, lack tanha (craving, aversion, and the resulting suffering), or are "enlightened by default" is, by my estimation, very low”. 9: Recursive Adaptation (blog on addiction policy)’s predictions for 2025. 75% of FDA approval of GLP-1 for a substance use disorder by 2029! 10: In my post on the economics of GLP-1 receptor agonists (eg Ozempic), I wrote about how they’re currently widely available because of a loophole suspending patents during a shortage, and predicted there would be a big fight when the shortage was over. Sure enough, the FDA tried to declare that the shortage of tirzepatide (a next-generation Ozempic relative) was over, compounding pharmacies sued, and tirzepatide is still available while the issue goes through the courts (and will the administration have an opinion?) Also, compounding pharmacy access startup Mochi says that they will continue to prescribe even if the shortage is over, using another loophole saying doctors can do this for specific individual patients in cases of medical necessity. This is an extremely fake use of this loophole, but will the government be willing to call their bluff? 11: Jacob Falkovich has a blog on dating advice, which he plans to turn into a book of dating advice. I can’t really comment on the accuracy (my dating strategy tends to look more like waiting for women to send me emails saying “I like your blog, would you like to go on a date?” which probably doesn’t generalize), but I’ve had many good interactions with Jake, and he has a beautiful family which means he must be doing something right. Also, Jake is poly, and I sometimes wonder if poly people are the only ones qualified to give dating advice: if you’re monogamous, you either met your future spouse quickly (in which case you have no experience), dated for years without meeting your spouse (in which case you can’t be very good), or aren’t looking for a committed relationship at all (which is just pickup artistry, and follows very different dynamics). Poly people are the only ones who can break out of this trilemma! 12: Christ And Counterfactuals is a blog on effective altruism from a Christian perspective. Some previous attempts at this have felt kind of forced, but the first post I read here was actually pretty interesting. Richard Swinburne (apparently “the world’s best Christian philosopher”), thinks that: “[One] reason why it is good that the human race should sometimes be in an initial situation of considerable ignorance about the causes and effects of our actions, is this. If God abolished the need for rational inquiry and gave us from childhood strong true beliefs about the causes of things, that would make it too easy for us to make moral decisions. As things are in the actual world, most moral decisions are decisions taken in uncertainty about the consequences of our actions. I do not know for certain that if I smoke, I will get cancer; or that if I do not give money to some charity, people will starve. So we have to make our moral decisions on the basis of how probable it is that our actions will have various outcomes—how probable it is that I will get cancer if I continue to smoke (when I would not otherwise get cancer), or that someone will starve if I do not give. Since probabilities are so hard to assess, it is all too easy to persuade yourself that it is worth taking the chance that no harm will result from the less demanding decision (the decision which you have a strong desire to make). And even if you face up to a correct assessment of the probabilities, true dedication to the good is shown by doing the act which, although it is probably the best action, may have no good consequences at all.” (Could a Good God Permit so Much Suffering? A Debate, pp. 52-53.) This is pretty galaxy-brained, but something galaxy-brained must be going on for God to tolerate the existence of evil at all, and this is a surprisingly natural extension of some common premises on the subject. 13: Swedish study: diagnosing the marginal patient with a psychiatric condition makes their life worse. Of the two mechanisms they looked at, stigma seems more involved than drug side effects. My opinion: this study was done on conscripts undergoing a mandatory psych evaluation for the army, who had no previous reason to think they had a psych disease and had not sought treatment. This is a different situation from somebody who comes to a psychiatrist asking for relief from specific symptoms they have noticed. Also, Sweden c. 2005 is a different culture from America 2025 in terms of how much stigma a psych diagnosis carries. I think it’s possible that if you never considered that you had psychiatric problems, and were suddenly given a diagnosis in 2005 Sweden and told you couldn’t serve in the army, that’s likely to destabilize your self-image more than a person who knows they’re depressed going to a psychiatrist in 2025 US and getting antidepressants. 14: RIP Felix Hill, research scientist at DeepMind and mentor to many in the AI community. You can read his suicide note here, though the obvious content warning applies. He says he took ketamine for mild anxiety and it plunged him into an incredibly deep depression that he couldn’t get out of; he leaves his story behind as a warning for others. I appreciate his warning, but I wish he had said more about what dose he used; different people’s ketamine doses vary by almost two orders of magnitude, I’d previously thought that the low doses were pretty safe and the high doses were sketchy, and I would like to know whether I should update or not. 15: RIP Max Chiswick, professional poker player, effective altruist, and ACX reader. 16: Adrian Dittman, a Twitter account widely accused of being Elon Musk’s alt, has been revealed to be . . . a guy named Adrian Dittman. Congrats to Maia Crimew and the Spectator for actually investigating this, unlike many other news sources which spread the Musk conspiracy theory. Also, the people involved got banned from X for some reason, maybe because this qualified as doxxing Dittman. 17: Related: Musk claims to be among the top players in the world at several computer games. A veteran Path of Exile gamer presents evidence that Musk faked his PoE2 accomplishments by hiring a Chinese guy to play on his account. Some Musk supporters in the comments suggest that maybe he hires the Chinese guy to level up his account, but his accomplishments (eg speedruns) are still his own? 18: Related: Sam Harris says he has been friends with Musk since 2008, but he noticed a sudden shift for the worse in his personality around 2020 which made it impossible to stay friends with him. He gives the example of Musk losing a bet with him that there would be 35,000+ COVID cases in the US, refusing to pay up, and launching personal attacks on Sam when asked to do so. What happened? Some theories: Musk turned right-wing, which ended his friendship with Sam for the same reason political differences have always ended friendships (but then what about the bet, which seems like objectively bad behavior?)
March 12, 2025 · Original source
Tirzepatide (Mounjaro®, Zepbound®)
Liraglutide (Victoza®, Saxenda®) …but liraglutide is noticeably worse than the others, and most people prefer either semaglutide or tirzepatide. These cost about $1000/month and are rarely covered by insurance, putting them out of reach for most Americans. …if you buy them from the pharma companies, like a chump. For the past three years, there’s been a shortage of these drugs. FDA regulations say that during a shortage, it’s semi-legal for compounding pharmacies to provide medications without getting the patent-holders’ permission. In practice, that means they get cheap peptides from China, do some minimal safety testing in house, and sell them online. So for the past three years, telehealth startups working with compounding pharmacies have sold these drugs for about $200/month. Over two million Americans have made use of this loophole to get weight loss drugs for cheap. But there was always a looming question - what happens when the shortage ends? Many people have to stay on GLP-1 drugs permanently, or else they risk regaining their lost weight. But many can’t afford $1000/month. What happens to them? Now we’ll find out. At the end of last year, the FDA declared the shortage over. The compounding pharmacies appealed the decision, but the FDA recently confirmed its decision is final. As of March 19 (for tirzepatide) and April 22 (for semaglutide), compounding pharmacies can no longer sell cheap GLP-1 drugs. Let’s take a second to think of the real victims here: telehealth company stockholders. Some compounding pharmacies are already telling their customers to look elsewhere, but not everyone is going gently into the good night. I’m seeing telehealth companies float absolutely amazing medicolegal theories, like: Compounding pharmacies are allowed to provide patients with a drug if they can’t tolerate the commercially available doses and need a special compounding dose. Perhaps our patients who were previously on semaglutide 0.5 mg now need, uh, semaglutide 0.51 mg. In fact, they need exactly 0.51 mg or they’ll die! Since the pharma companies don’t make 0.51 mg doses, it has to be compounded and we can still sell it.
But the compounders aren’t the only ones boxing clever. Novo Nordisk and Eli Lilly, the pharma companies behind semaglutide and tirzepatide respectively, have opened consumer-facing businesses about halfway between a traditional doctor’s appointment and the telehealth/compounder model that’s getting banned. So for example, Lilly Direct offers to “find you a doctor” (I think this means you do telehealth with an Eli Lilly stooge who always gives you the meds you want) and “get medications delivered directly to you”. The price depends on dose, but an average dose would be about $500 - so about halfway between the cheap compounding price and the usual insurance price. Not bad.
Twitter

Twitter is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between April 30, 2021 and July 26, 2024. The archive places it in contexts such as "Were he to live in an age of Facebook and Twitter"; "Facebook, Google, YouTube, and Twitter were already blocked"; "I think Twitter is a different and unique challenge". It most often appears alongside Twitter, America, Elon Musk.

Article page
Twitter
Mention count
5
Issue count
5
First seen
April 30, 2021
Last seen
July 26, 2024
April 30, 2021 · Original source
The problem with the concept of carrying capacity – impossible to define or know when we’ve surpassed, until after the proverbial moment when killing one mosquito or dovekie too many plunges us into everlasting fire and brimstone – is that it seems mostly like a mood affiliation thing. Consider this: when you look out at the bird feeder hanging in your backyard (Bay Area people living in closets, use your imagination here), do you see a blissful symbiotic coexistence of the human world and nature, with humans generously giving of our growth-accumulated abundance to help the birds flourish? Or do you see a dystopian struggle where innocent creatures pushed to the brink of death by our traffic and pesticides and housecats must rely on meager scraps for survival? There isn’t really a right view here, I don’t think, just a predilection for seeing what matches your intuition and telling a story about it. Given the life story Mann depicts for Vogt, it’s not hard to see why he would lean toward the pessimistic take. From the childhood marred by a philandering father who left his family in a cloud of scandal and ruin, to the adult life spent stumbling from one bourgeois non-occupation (theater critic, bird watcher, government mole rooting out Nazis in South America) to the next, to the childlessness and divorce, Vogt seems happiest when he is away from any humans, whether tromping through pre-suburbanized Long Island, or alone with the guano-producing birds on the desolate coast of Peru. Were he to live in an age of Facebook and Twitter, he would definitely be that guy reposting memes that COVID is finally letting our planet "heal."
In Caliban’s War, the second book in The Expanse series, there’s an excellent metaphor for how having more smart people working on problems fails in an atmosphere of increased complexity, offered by fictional future UN government higher-up Chrisjen Avasarala: "You take part of a problem and you put it somewhere, get some people working on it, and then you get another part of the problem and get other people working on that. And pretty soon you have seven, eight, a hundred different little boxes with work going on, and no one talking to anyone because it would break security protocol." Except instead of security protocol, you could substitute any number of Moloch-y reasons, or just regular old-fashioned human tunnel vision. If there’s one thing we can take from the Prophets, it’s their focus on trying to understand complex systems holistically, Chesterton’s Fence style, instead of as piecemeal problem-boxes in a hundred siloed experts’ rooms. Each of today’s systems is more like Chesterton’s Maze of Forking Paths, where pulling out a brick here (say, trying to prioritize equity in vaccine distribution) leads to a catastrophic tunnel collapse there (more deaths, including in the historically underprivileged populations you were trying to save). The Prophets may have a less than stellar track record of questioning new technologies, but I think they’re right that the Wizardly tendency to reduce complexity to a discrete number of problem-boxes can only get us so far – and, as we saw with the myriad of expert box factories talking past each other in the global COVID pandemic response, it can harm as well as help. If we’re always hotfixing as our big picture grows bigger and more complex, we’re also always creating new inadvertent problems with our hotfixes, and are in ever more danger of forgetting about that one critical problem box until it’s too late.
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
September 13, 2023 · Original source
Definitely no. For one thing, he usually ends up in an industry by coincidence. He went into aerospace because he wanted to pull a publicity stunt with mice on Mars, tried to buy a rocket from the Russians, they were going to rip him off, and he decided to build a better rocket to spite them. He went into cars because the founders of Tesla asked him for an investment, he liked the company, and then he thought they were doing a bad job and he needed to take over. He took over Twitter because he was addicted to Twitter, got a seat on the board, and then the other board members said he had to behave and he didn’t want to.
I think this level of intensity - combined with a high-even-if-not-unprecedently-high level of engineering ability - is enough to explain why he succeeds despite his flaws. Do you think Elon will succeed at X/Twitter? I lean towards yes.
On the other hand, this time Ashlee Vance himself is skeptical. He says:
September 18, 2023 · Original source
1: Comments From People With Personal Experience 2: ...Debating Musk's Intelligence 3: ...Debating Musk's Mental Health 4: ...About Tesla 5: ...About The Boring Company 6: ...About X/Twitter 7: ...About Musk's Mars Plan 8: ...Comparing Musk To Other Famous Figures 9: Other Comments 10: Updates
I’ve heard via my personal network (which I trust more than this Ashlee Vance book) that Musk did used to drill down into engineering level decisions at SpaceX. Whether he’s actually extremely technically proficient, I don’t know. I’ve also heard this has slowed down a lot in the last few years since he’s focused on Twitter. (Note that the above is hearsay, I’ve never met the man myself or worked for any of his companies).
heliotropic on Twitter writes:
July 26, 2024 · Original source
If you’re a follower of U.S. news outlets, you’ve seen some big stories unfolding over the past year: The unprecedented four criminal indictments lodged against former President Trump. The ongoing AI explosion. The backlash against “DEI,” “woke,” and “cancel culture” as exemplified by Elon Musk’s purchase and rebranding of Twitter to “X.”
Making the sentence for all crimes identical: Mandatory death penalty9. As far as perfidious methods to deliberately destroy due process and engineer mass executions go, the Law of 22 Prairial is pretty much unmatched in human history. And yet: In the roughly two months of the law’s existence, about one-fifth of defendants were still acquitted! No such good fortune exists in Gitmo. The White Hats’ secret tribunal is a tribunal of blood. In three years of activity, as far as I know exactly one person has escaped conviction: Former Attorney General Jeff Sessions, freed after a direct intervention from Trump. A tiny handful of others have received decades-long prison sentences, but even they tend to meet bad ends. Bill Clinton received a life sentence, only to mysteriously die in prison, perhaps murdered by his daughter Chelsea, who wasn’t really his daughter, but nevertheless soon wound up executed herself. Not only does the rate of death sentences at Gitmo seem to exceed 90 percent, Baxter makes very little effort to portray the proceedings as fair or just. Upon arrest, instead of being read their rights, detainees are informed that they have no rights, and are instead “enemy combatants.” Yet despite being classified as “enemy combatants,” defendants are almost without exception charged with treason. The U.S. Constitution defines treason narrowly as levying war against the United States, or giving aid and comfort to its enemies, and requires at least two witnesses to the same specific act, but in Gitmo the label is invoked with a liberality that would make Robespierre blush. “Traitors” have been arrested and convicted for telling troops not to attend Trump rallies and for ruling against Donald Trump in court. Defense attorneys are denied access to evidence pre-trial, and many defendants get no lawyers at all. Trials work a lot like Phoenix Wright, in that at any point the three-officer panel10 can simply declare they’ve seen enough evidence and pronounce a conviction with death sentence immediately. In the case of former Tom Hanks co-star, this has happened within five minutes. Appeals are non-existent. The actual executions sometimes involve tormenting the condemned with fake escape attempts or pardons: The driver told Whitmer he needed to make a pitstop to grab her “exoneration paperwork.” Then Whitmer saw the clearing and the gallows and Vice Adm. Crandall. And the hangman and a Navy chaplain standing atop the gallows. “You lied to me,” Whitmer bellowed. “Minor error, not a lie,” the driver replied. […] The admiral instructed the hangman to flip the switch, and a second later, Whitmer was swinging from the rope, a guttural gurgling sound escaping her lips. She was officially pronounced dead several minutes later. “Another Covid queen out of the way,” Adm. Crandall said. During the treason trial of Hillary Clinton crucial evidence is provided by former campaign manager John Podesta, who accepts a plea deal for life in prison in return for testifying about Clinton’s child-trafficking activities. But after Clinton had safely been hanged, the military tribunal simply decided to revoke Podesta’s plea deal because, well, they felt like it. “Even though he’s not prosecuting Podesta’s case, Vice Adm. John G. Hannink made the decision to renege on the deal. He’s the one who offered it. The severity of Podesta’s crimes matched Clinton’s—a lot of stuff they did in tandem, together. When you think about it, there’s really no reason why he should get special treatment. He’s a sodomist [sic.]11. Before breaking the deal, he called Trump,” our source said. But Trump, our source noted, recused himself from the decision-making process, as he didn’t want his personal feelings of the defendant to interfere with military justice. […] “If the court wants him to hang, let him hang,” Trump reportedly said. As it happens, John Podesta was actually executed by firing squad. But hey, at least he got a trial. Sometimes, particularly evil members of the Deep State are simply beaten to death in their cells, or thrown overboard. The figure of Vladimir Putin is also a vessel for fans’ darker desires. Trump and his American allies, being properly heroic, at least take down their foes gradually. Putin’s Russians, on the other hand, live up to movie stereotypes. The Army … pulled the condemned from their cells 25 at a time, binding the criminals to logs staked in the ground and blindfolding them. They had received no trials, last meals, Last Rites, or final words. A firing squad taught them the consequences of vaccine adherence. The Army didn’t bother removing the corpses before lining up the next 25; they simply let the dead bodies flop to the ground and forced the next group to witness the ineluctable fate awaiting them, the outcome of their insouciance12. What to make of all this? Honestly, I’m not entirely sure, and the takeaway might simply be “Michael Baxter needs to mix it up to keep the site interesting.” It might also speak to the bewildering complexity of modern life and the desire for something simpler and more cinematic. As people sometimes complain, Nothing Ever Happens. But on RRN, the Happening is relentless and constant. The normal legal system is aggravatingly glacial, taking years to resolve cases and often imposing meager sentences when a case finally concludes. Most of one’s political enemies, even if they lose an election, simply lateral to a high-paying private sector job or at worst fade into obscurity. But in a real, raw legal system, evil is sniffed out with much greater alacrity; the bad people are so obvious and their crimes so glaring that they can be taken out extrajudicially with no worry about a miscarriage of justice. The apparently-complex conspiracy cinematic universes is actually appealing because it makes the world far, far simpler. The bad people are all maximally bad, deserving of hastily-dispensed maximum justice. Some of this is worrisome, too: If thousands of relatively ordinary people are willing to believe in ad-hoc military tribunals executing people with minimal due process for crimes like “ruling against Donald Trump in court,” that could be a sign that modern constitutional society is a more superficial veneer than one would hope. The World’s Laziest Conspiracy One of the most striking things about both Real Raw News and the Qanon movement it spun off from is that in some ways they are un-conspiracies. Your more traditional conspiracy, about the Rothschilds or the World Economic Forum or the Lizard People, tells you that normal political engagement is pointless, as all that really matters is confronting and defeating the hidden forces manipulating or controlling events. But RRN is a conspiracy theory that calls for total inaction. RRN believers don’t need to raise money or write letters to the editor or join political activism groups or even vote. The only thing expected of an adherent is to “trust the plan.” They aren’t even waiting for a promised future deliverance. Deliverance is, in fact, happening right now – merely off-screen. It’s actually funny to me that the (official) press freaks out so much about Qanon, and its potential to inspire violence. Qanon and RRN tell the public that whatever has them down and depressed shouldn’t, because it’s all fake, and there are unseen heroes protecting them in the shadows. Don’t worry, just have faith and know things will work out. Real Raw News is the opiate of the digital masses. Real Raw News is the exact sort of conspiracy theory that the Deep State, if it exists, should want to exist and be popular. It’s the sort of conspiracy that the Deep State, if it exists, might deliberately invent. Do I think that’s what happened here? Not at all – Real Raw News is way too much work for a government employee. Trump Will Never Die But what about five years from now? What if there were some technological change that would make it far, far easier to produce evidence of a sweeping conspiracy theory? That’s right, this review is actually about AI13. The rise of realistic artificial intelligence has created a lot of fretting about deepfakes, and it’s also created a lot of fretting about porn. Will young men really bother with the pain and difficulty and awkwardness of dating in real life, when they can just create a custom AI girlfriend to their exact specifications, then simulate sex with her using virtual reality? Will women bother with seeking out a boyfriend if they can use an LLM to give them perfect 24/7 empathy and emotional validation? Questions of sex and relationships are converging on Robert Nozick’s experience machine – will people still seek the real thing if artificial substitutes are increasingly realistic as alternatives? But for some reason, nobody is asking this about the news. Oh, sure, people have fretted that a deepfake video might smear a person’s reputation or swing an election. But as the AI revolution continues, a lot more becomes possible. Remember in 2022, when a homeless guy broke into Nancy Pelosi’s home and attacked her husband with a hammer? For a while, conspiracies flourished that Paul Pelosi was actually having some kind of erotic tryst with his attacker, and that police body camera footage might confirm this. The footage came out and, of course, offered no evidence of this. But now imagine a world where, on Twitter, an anonymous source claims that they have the real body camera footage, and it does show that Paul Pelosi was having a lovers’ quarrel with his attacker. The other, mundane footage is a deepfake, released by police to cover things up, or invented from scratch by the press or the Democratic Party or both working together. In this world, how many people end up believing fabricated proof of Paul Pelosi’s gay lover? And before you dismiss this as all totally ridiculous, remember that lots of people believed this story with no evidence at all. Many thousands of people have deluded themselves into thinking that Real Raw News is true simply because they badly want it to be true. It indulges their personal political beliefs, affirms the just-world fallacy, and lets them feel as though they possess “secret” knowledge of the world, simply by reading a blog nobody else takes seriously. But in a sense, all of us have a little of the Real Raw News believer in us. We’re prone to confirmation bias – we like reading stories and studies that confirm our pre-held beliefs, and we’re more likely to avoid or ignore those that don’t. Sometimes, we get too excited and fall for stories that are misleading, or out of context, or dishonestly presented. Sometimes, we have radically different interpretations of the same event caught on camera. Even if we know the world isn’t fair, we relish stories that let us pretend otherwise. So…how are those biases going to work when anyone can quickly create hyper-realistic looking “proof” for any story? Already, AI-fabricated images and videos are enough to bamboozle your mom on Facebook. Soon, they might be realistic enough to fool everybody without special training, and eventually they might be so realistic they can fool just about anyone. Right now, Real Raw News is a simplistic WordPress site that uses stock photos for its imagery. But with us approaching a future where intelligence itself is too cheap to meter, we may not be far from a world where every story, however preposterous, can have a convincing 4k video of it happening. Donald Trump can be president forever, with all the evidence one could ever want. Every day of Hillary Clinton’s military tribunal will have a full day of court footage, plus a condensed highlight reel for the people who want to skip boring legal procedure. Every Marine/FEMA battle in Maui will have authentic-looking combat footage. Every Gitmo execution will be proven through “leaked” bootleg recordings of gallows and firing squads. Imagine you are an ordinary, mildly engaged American citizen. You live far from the halls of power, you work an ordinary job, and whatever your feelings on political issues, you rarely see elections translate in a clear way to your own daily life. You might be interested in Washington, but Washington really isn’t that interested in you. Online, the world throws a million potential narratives at you. In some of them, the world is a confusing mess of moral gray areas. In others, the people you care about are winning. But in some narratives, you’re the hero, the people you like do good things, and the bad guys get what they deserve. The superficial evidence for all of these narratives is about equally convincing, at a glance. Look outside, and it’s hard to see the impact of any of the stories. Your entire understanding of reality is mediated through what sites you choose to read and what videos you choose to watch. As a politically marginal person, it won’t matter what you as an individual choose to believe. So, what happens if you choose to believe the story you find most enjoyable? And what if millions of others choose the same? 1 “Wait a minute, this is about a fake news website? Why is it in this contest?” Excellent question! To that, I offer several answers: A collection of fake news blog posts may as well be considered a long-running series of short stories, and I hope that we’d be allowed to review the collected short stories of an author even if they were never technically compiled into a book.
Tylenol

Tylenol is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between December 22, 2021 and October 30, 2025. The archive places it in contexts such as "Like every medication, including Tylenol, aspirin, etc"; "go home, take some Tylenol and come back if you don’t feel better"; "Avoid Painkillers, Including Tylenol". It most often appears alongside FDA, US, Benjamin Jolley.

Article page
Tylenol
Mention count
5
Issue count
5
First seen
December 22, 2021
Last seen
October 30, 2025
December 22, 2021 · Original source
What are the risks? Like every medication, including Tylenol, aspirin, etc, Luvox has some common minor side effects and some rare major ones. But let’s step back a second. Fluvoxamine is a bog-standard SSRI. Its side effects are generic SSRI side effects. We give SSRIs to 30 million people a year, or about 10% of all Americans. As a psychiatrist, I’m not supposed to say flippant things like “we give SSRIs out like candy”. We do careful risk-benefit analysis and when appropriate we screen patients for various risk factors. But after we do all that stuff, we give them to 10% of Americans, compared to 12% of Americans who got candy last Halloween. So you can draw your own conclusion about how severe we think the risks are.
January 27, 2022 · Original source
But “go home, take some Tylenol and come back if you don’t feel better” is actually quite an effective strategy in this GP-as-gatekeeper model. Most of your patients feel better and don’t come back, as you couldn’t have done anything for them anyway. This keeps costs down and keeps the emergency room just for actual emergencies.
April 13, 2022 · Original source
Only the sinister foreign “black licorice” contains glycyrrhizin. The red licorice eaten by normal red-blooded Americans is (as per American tradition) made out of corn syrup derivatives with no real licorice whatsoever, and should be fine. Avoid Painkillers, Including Tylenol (Tier 2) Doctors have been gradually chipping away at pregnant women’s ability to use pain medication. First it was “don’t use opioids, your baby could have birth defects”. Then it was “and don’t use ibuprofen, your baby could have kidney problems”. Then it was “and don’t use too much aspirin either, your baby could get cardiovascular problems”. That left Tylenol (aka Panadol, paracetamol, acetaminophen, etc) as the only pregnancy-safe pain reliever. Well, bad news…
Doctors have been gradually chipping away at pregnant women’s ability to use pain medication. First it was “don’t use opioids, your baby could have birth defects”. Then it was “and don’t use ibuprofen, your baby could have kidney problems”. Then it was “and don’t use too much aspirin either, your baby could get cardiovascular problems”. That left Tylenol (aka Panadol, paracetamol, acetaminophen, etc) as the only pregnancy-safe pain reliever. Well, bad news…
Last year, Nature Reviews Endocrinology published Consensus Statement: Paracetamol Use In Pregnancy - A Call For Precautionary Action, by ninety-one leading scientists. It argued that Tylenol use during pregnancy might cause neurodevelopmental and urogenital disorders in children. They argue that Tylenol babies have higher risk of abnormal hormone profiles, abnormal urinary tract development, and ADHD. What’s their evidence?
April 16, 2024 · Original source
Causes minor side effects for some people, same scale as Tylenol: 30%
October 30, 2025 · Original source
18: The politics of RFK Jr’s Tylenol announcement (X). RFK “overpromised an autism report with a tight deadline to his base and to Trump, who is curious about autism in a sort of hobbyist way.” He originally planned to blame vaccines, but this would have required him to do something about them, and he didn’t have enough political capital for that. The Tylenol announcement let him satisfy his conspiracy theorist base without offending any powerful lobbies - Tylenol is generic, doesn’t make Big Pharma any money, and even the Tylenol manufacturers don’t care that much about an extra easy-to-ignore warning against use during pregnancy (hint for Europeans who don’t understand this story: Tylenol = paracetamol). I continue to believe the real reason for rising autism rates is increased diagnosis.
DALL-E2

DALL-E2 is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between April 18, 2022 and July 08, 2025. The archive places it in contexts such as "The drop corresponded to three big AI milestones. First, DALL-E2, a new and very impressive art AI"; "DALL-E2: “A giant Statue Of Responsibility, standing in a city harbor”"; "DALL-E2 is bad at “compositionality”". It most often appears alongside China, Gary Marcus, Google Imagen.

Article page
DALL-E2
Mention count
4
Issue count
4
First seen
April 18, 2022
Last seen
July 08, 2025
April 18, 2022 · Original source
The drop corresponded to three big AI milestones. First, DALL-E2, a new and very impressive art AI.
This raises the eternal question of “exciting game-changer” vs. “incremental progress at the same rate as always”. These certainly don’t seem to me to be bigger game changers than the original DALL-E or GPT-3, but I’m not an expert and maybe they should be. It’s just weird that they used up half our remaining AI timeline (ie moved the date when we should expect AGI by this definition from 20 years out to 10 years out) when I feel like there have been four or five things this exciting in the past decade.
June 23, 2022 · Original source
DALL-E2: “A giant Statue Of Responsibility, standing in a city harbor”. I myself prefer civic monuments that look less like Sauron, but tastes may differ. I don’t really have a strong opinion on this. I can think of ways that people are victims and it’s important to acknowledge that and treat them appropriately, and also ways that taking responsibility and not wallowing in victimhood is psychologically healthy and important. Probably San Francisco progressives are too far to the victimology end of the scale and could benefit from taking Shellenberger’s thoughts on the matter seriously. I still feel conflicted on this without really being able to verbalize why.
September 12, 2022 · Original source
DALL-E2 is bad at “compositionality”, ie combining different pieces accurately. For example, here’s its response to “a red sphere on a blue cube, with a yellow pyramid on the right, all on top of a green table”.
At the time, I wrote: I’m not going to make the mistake of saying these problems are inherent to AI art. My guess is a slightly better language model would solve most of them…for all I know, some of the larger image models have already fixed these issues. These are the sorts of problems I expect to go away with a few months of future research. This proved controversial. Gary Marcus in particular has emphasized how challenging compositionality is for modern language and image models: @sama @gdb @Plinz @ylecun, \n\nEach of you ridiculed my recent title, but this is what the article was actually about: compositionality.\n\nYes, there are many kinds of progress in other directions. \n\nBut compositionality is at the core of intelligence. \n\nNo AGI without it. ","username":"GaryMarcus","name":"Gary Marcus","profile_image_url":"","date":"Sat Apr 09 04:34:37 +0000 2022","photos":[],"quoted_tweet":{"full_text":"Compositionality *is* the wall. \n\nEven “red cube” and “blue cube” on their own are represented unreliably; not one of ten images correctly captures the full phrasal description.\n\nThe images are beautiful, but no match for the precision of language. https://t.co/uvoXUtETwi","username":"GaryMarcus","name":"Gary Marcus"},"reply_count":0,"retweet_count":7,"like_count":54,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> And one of my commenters, Vitor, asked: Why are you so confident in this? The inability of systems like DALL-E to understand semantics in ways requiring an actual internal world model strikes me as the very heart of the issue. We can also see this exact failure mode in the language models themselves. They only produce good results when the human asks for something vague with lots of room for interpretation, like poetry or fanciful stories without much internal logic or continuity. Not to toot my own horn, but two years ago you were naively saying we'd have GPT-like models scaled up several orders of magnitude (100T parameters) right about now (https://slatestarcodex.com/2020/06/10/the-obligatory-gpt-3-post/#comment-912798). I'm registering my prediction that you're being equally naive now. Truly solving this issue seems AI-complete to me. I'm willing to bet on this (ideas on operationalization welcome). I responded to Marcus here, and I responded to Vitor by making a bet on whether AI image models could draw some compositionality-heavy pictures by 2025. The specific terms we agreed on: My proposed operationalization of this is that on June 1, 2025, if either if us can get access to the best image generating model at that time (I get to decide which), or convince someone else who has access to help us, we'll give it the following prompts: 1. A stained glass picture of a woman in a library with a raven on her shoulder with a key in its mouth 2. An oil painting of a man in a factory looking at a cat wearing a top hat 3. A digital art picture of a child riding a llama with a bell on its tail through a desert 4. A 3D render of an astronaut in space holding a fox wearing lipstick 5. Pixel art of a farmer in a cathedral holding a red basketball We generate 10 images for each prompt, just like DALL-E2 does. If at least one of the ten images has the scene correct in every particular on 3/5 prompts, I win, otherwise you do. DALL-E can’t do any of these: If I were being kind, I would give it the farmer in the cathedral. But I am being unkind, so the farmer in front of the cathedral doesn’t count. II. There are now at least four more AI image models available: Google Imagen announced May 2022.
It still fails the library scene, although it does better than DALL-E2 in realizing that the picture itself should be in the style of stained glass. It still fails the fox scene, although it does better than DALL-E2 in at least realizing that the fox should have the lipstick.
July 08, 2025 · Original source
DALL-E2 had just come out, showcasing the potential of AI art. But it couldn’t follow complex instructions; its images only matched the “vibe” of the prompt. For example, here were some of its attempts at “a red sphere on a blue cube, with a yellow pyramid on the right, all on top of a green table”.
We generate 10 images for each prompt, just like DALL-E2 does. If at least one of the ten images has the scene correct in every particular on 3/5 prompts, I win, otherwise you do. Loser pays winner $100, and whatever the result is I announce it on the blog (probably an open thread). If we disagree, Gwern is the judge.
Why are you so confident in this? The inability of systems like DALL-E to understand semantics in ways requiring an actual internal world model strikes me as the very heart of the issue. We can also see this exact failure mode in the language models themselves. They only produce good results when the human asks for something vague with lots of room for interpretation, like poetry or fanciful stories without much internal logic or continuity.
Dexedrine

Dexedrine is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between January 25, 2021 and November 01, 2024. The archive places it in contexts such as "Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice"; "Dexedrine is an older formulation with pure d-amphetamine"; "James et al switch children back and forth between Adderall and Dexedrine". It most often appears alongside Vyvanse, Adderall, FDA.

Article page
Dexedrine
Mention count
4
Issue count
4
First seen
January 25, 2021
Last seen
November 01, 2024
January 25, 2021 · Original source
Treating ADHD with amphetamines was hardly a new invention. Psychiatrists had been doing it since the 1930s, albeit with slightly different drugs. Remember, many organic chemicals come in two versions, a "right-handed" or "d" version and a "left-handed" or "l" version. Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice throughout the mid-20th century. So why was it Adderall - a weird combination of four different salts selected kind of at random by a sketchy diet pill company - that caught on?
I'm not sure. My best guess is good timing plus good advertising. In the early 20th century, ADHD was called "minimal brain dysfunction" and diagnosed only in the most extreme cases. A few children with absolute and total inability to function at all got diagnosed and given Benzedrine or Dexedrine; everyone else was left to fend for themselves. As far as I know, this wasn't because doctors had a principled commitment only to diagnose extreme cases - I found a paper from 1975 arguing that up to 5 - 10% of children probably had minimal brain dysfunction, the same number estimated to have ADHD today. Parents just didn't know about it and didn't really have "take my kid to a psychiatrist" in their set of plausible options to consider.
Even if we agree that amphetamines are the right treatment for ADHD (many people don't!), how concerned should we be that the particular amphetamines we use are a random mix of salts selected by sketchy 1950s diet-pill peddlers? Dexedrine is an older formulation with pure d-amphetamine (sulfate). No l-amphetamine, no weird combination of salts. Should we just use that?
January 31, 2021 · Original source
1. Thanks to everyone who commented on the amphetamines thread. The main things I learned: another way of thinking about the difference between racemic, d-, and meth- amphetamine is the ratio of central to peripheral effects. One major reason druggies prefer methamphetamine to unsubstituted is because it’s easier to make. I was wrong about Vyvanse; it gets cleaved by red blood cells, not the liver. And one reader links me to this conspiracy theory (sorry, it’s actually very reasonable, I just can’t help thinking of it that way) that Vyvanse doesn’t have superior pharmacokinetics to other amphetamines at all, and it’s all just Dexedrine + hype; I haven’t had enough time to examine the theory in depth but am interested in people’s thoughts.
November 30, 2022 · Original source
Doses needed for consistent weight loss/maintenance are much higher than for, say, ADHD. Plus every time the damned things wear off, ALL the hunger arrives at once. And you have to let them wear off, because otherwise sleep is terrible. (I was prescribed Dexedrine for weight loss several decades ago by a crazy doctor, and am now on a decently high dose of Vyvanse for ADHD).
November 01, 2024 · Original source
This was before they invented what we would call antidepressants today; Dexedrine is an amphetamine related to Adderall. 24: Congratulations to Open Philanthropy, the biggest effective altruist foundation… …whose grantee David Baker recently won a Nobel Prize for his research on synthetic proteins. Potential applications include new drugs, vaccines, and materials. 25: Rich Kid Memes And The Online Culture Of The One Percent. Rich people who want to signal group membership to other rich people online can’t boast about how rich they are; that would be gauche. Instead, they’ve settled on the solution of making fun of rich people in hyperspecific language that proves familiarity with the culture. 26: Tap Water Sommelier: Vladimir Putin has two sons, ages 5 and 9. They are kept in luxurious but total isolation from the outside world and raised by flunkies who are too scared to punish/restrain them in any way. Also some discussion of an unexpected historical analogue. 27: Experiment from Colombia: replacing experienced teachers with less-experience but higher-scoring-on-tests teachers significantly decreased student performance. Got to admit I was expecting the opposite of this, I’d seen US data saying that experience didn’t matter and teacher intelligence did. Looking over this more, I find lots of studies on both sides and will go back to agnosticism on this question until someone I trust investigates further. 28: Large scale-formal Intellectual Turing Test finds that people can imitate partisans effectively; ie nobody on either side can tell the difference between a Democrat arguing for Democrat values vs. a Republican-pretending-to-be-a-Democrat arguing for Democrat values (and vice versa). This study used a 100 word essay on why you supported your party (you can see if you can do better here), but past attempts with different structures (religion, vegetarianism, polyamory) have shown broadly the same results. The researchers try to put this in the context of various studies showing that people do misunderstand their opponents (eg think they’re more extreme, underestimate the level of common ground), but it seems like intellectual Turing Tests aren’t a good way to measure or tease out this misunderstanding. 29: Congratulations to Substacker WoolyAI for doing the impossible and providing a genuinely novel and interesting (to me) take on pickup artistry: 30: Did you know: if you Google “cool websites”, our subreddit (r/slatestarcodex) is the first result. 31: Moshe Koppel, who works at the intersection of computer science and Talmud, is writing a series of posts (presumably) based off of my Every Bay Area House Party, titled Jerusalem Area House Party (it’s multiple part, you have to go to the main Substack page to find the others). I won’t necessarily link everyone who riffs off one of my posts - but honestly I probably will if you also have a Wikipedia page that describes you as working on computational Talmudology. 32: David Roman says it’s a myth that Arabic scholars rescued and preserved the works of the great classical authors. 33: Medications often decrease “secondary endpoints” (eg stroke, heart attack), but the holy grail of pharma studies is proving that a certain drug decreases all-cause mortality. This is much harder (not all heart attacks kill people, and people die from lots of other things), but is the strongest possible endorsement for the drug (without it, you might worry that it only prevented non-fatal heart attacks, or that it killed as many people through side effects as it saves through heart attack prevention). Even great medications that we’re confident in can’t always clear this bar. But a new JAMA article adds another member to this select club: Adderall decreases all-cause mortality in ADHD, probably because it prevents drug addiction, car accidents, and impulsive actions. 34: Before the Gulf War got in the way, Saddam Hussein was building some crazy mosques: 35: Italy bans surrogacy - quite strictly, too, Italians aren’t even allowed to go abroad and do it. I am so sorry for all the Italians who will never get to be mothers and fathers because their government hates progress. You might hope that, whatever the other disadvantages of anti-immigrant parties, at least they’re incentivized to let natives have children, but looks like they can’t even get that one right. Starting to wonder whether the trains even run on time. 36: Elsewhere in “Italy sucks” news - did you know Italy’s tax code effectively bans startups? Companies are taxed before making any money, based on how many assets they have. If they have lots of assets but aren’t making money (eg because they’re still doing research / in stealth) then tax officials get confused and hostile and run increasingly punitive audits. Related: size of the European tech sector. It’s the red line on this chart; if you can’t see a red line at your screen resolution, then you’ve learned something important about the the EU tech sector. 37: Seen on @cremieuxrecuel’s twitter (preliminary, needs replication): Jews may have gone from 65-29 Democrat/Republican in 2020 to 58-40 this election. 38: Extelligence has a post responding to my critique of the cultural Christianity argument (among, uh, many other things), but I don’t really think it connects. I’m not telling atheists they can’t go to church/synagogue if it makes them feel happy and fulfilled - I’ve done this myself sometimes. My post was meant to argue against the claim that, for pragmatic reasons, atheists should support the Christianization of society as a defense against Islam or postmodernism or some other philosophical enemy. 39: Related: Extelligence is finally going for their Trust Assembly project/idea/startup for online consensus-based truth-seeking (I think something like a cross between Community Notes and Wikipedia, but as a browser extension, and for everything). He’s looking for potential developers/testers/users. 40: Jiankui He is the Chinese geneticist who made history with the first germline gene editing in humans (resulting in three babies supposedly immune to AIDS, although nobody has tested this). China sentenced him to three years in prison for unauthorized experimentation, but now he’s out of jail, has an English-language Twitter account, has a new lab, wants to work on Alzheimers, and seems pretty based (although not infinitely based): 41: Anthropic has a new version of their AI Claude which can use your computer. You give it permission, put it on a virtual desktop, and ask it to do things for you (eg “please find and download a picture of a cat” or “please research these ten things and put them in a text file”.) It moves your cursor, browses the Internet, and creates and saves files. People keep saying they’ll care about AI “when it operates autonomously” or “when it becomes an agent”. But this is a trivial barrier, and one which Computer Use Claude has arguably already passed. So far this feature is limited to developers (though anyone with computer knowledge can sign up for it) but I expect it to be the near future of consumer AI, to get better quickly, and to shade gradually into the “autonomous” “agentic” AI that you all think will require a paradigm shift. 42: Claim (from the IDF): Hamas faked polls showing that most Palestinians supported the October 7 attack; the real numbers are 31% in favor, 64% against. 43: Otto von Bismarck wanted to trick France into declaring war on Germany. In order to provoke the French, he sent the Ems Dispatch, a statement describing recent diplomatic events in a way that sounded maximally offensive. The French were so offended that “crowds” in Paris demanded war, and the Franco-Prussian War was declared soon afterwards. The part of this that I find most interesting is the text of the dispatch itself, which read: After the news of the renunciation of the Prince von Hohenzollern had been communicated to the Imperial French government by the Royal Spanish government, the French Ambassador in Ems made a further demand on His Majesty the King that he should authorize him to telegraph to Paris that His Majesty the King undertook for all time never again to give his assent should the Hohenzollerns once more take up their candidature. His Majesty the King thereupon refused to receive the Ambassador again and had the latter informed by the Adjutant of the day that His Majesty had no further communication to make to the Ambassador. I’m fascinated by the idea that only 150 years ago, it was obvious that if someone sent you this statement, you had to declare war or abandon all honor. If I read it carefully, I can sort of parse out that it sounds like the Prussians are unhappy, but that’s the most emotion I gather from it. Anyway, the Franco-Prussian War led to World War I which led to World War II - so if you don’t like 50 million people dying and the total devastation of Europe, blame this statement about ambassadors. 44: The first use of artificial insemination in humans: The first recorded case of artificial insemination by donor didn’t occur until 1884, when Dr. William Pancoast decided to treat a couple’s infertility by secretly inseminating the woman with sperm obtained from a medical student. The insemination happened while the patient was under anesthesia and Dr. Pancoast did not tell her what had occurred. She gave birth to a baby boy nine months later, but it was several years before the doctor finally confessed to her husband what he had done. Neither man ever informed the mother. It was 25 years later the result of this case was published. Dr. Pancoast was roundly condemned for his actions, but it did open the door for consensual sperm donor insemination. 45: ClearerThinking administers several personality tests to the same people to learn more about their comparative accuracy. I am most interested in their finding that tests with “factors” (eg the Big Five, where you rate people on a numeric scale) are inherently more accurate than those with “types” (eg Myers-Briggs, where you assign someone a specific category) and that, adjusting for this, Big Five is no more predictive than the Enneagram: 46: In 2022, I wrote Whither Tartaria, where I asked why ornate classical styles switched to more austere modernist styles around 1900 - 1950 in a variety of different arts (painting, architecture, literature, poetry, etc). I proposed seven theories, but was unsure which if any were true. Since then, Samuel Hughes of Works In Progress has been investigating. In May, he wrote a well-researched article showing that it wasn’t just increasing cost, because ornate classical architecture now costs less than ever. Now in a new article he demolishes a different theory - it’s not just decreasing cost (and subsequent lack of ability to signal wealth) - because costs didn’t decrease in several other arts, and the change was led by artists with rich people as reluctant followers. He concludes: Modernism may well be a status game of some kind; it may well signal taste more than it signals wealth; and this latter feature may be one of the things that distinguishes it from older artistic styles. But the mechanism by which this change came about must be different to the one Alexander describes. 47: Sort of kind of related - When Hamilton Lost Its Snob Appeal. The musical Hamilton was briefly an artistic/cultural phenomenon, but tastemakers eventually switched to making fun of it. Why? Rob Henderson says it happened after ticket prices came down and the common people could enjoy it. I disagree: everyone I knew who was into Hamilton got into it from the free online soundtrack long before they’d seen the show; I think this is more likely the usual fad cycle where anybody who’s too into yesterday’s fad is behind the curve and therefore uncool. 48: Related: Why are people such jerks to public intellectuals? And more. I agree this is a great mystery. 49: Some prominent Substack psychiatrists doing a video Q&A, submit your questions here. 50: Naomi Kanakia: The Literacy Delusion had a number of explanations for why reading books seemed to be so much worse for human beings (in terms of emotional wellness and productivity) than other forms of narrative entertainment, but its main theory was the integration hypothesis. That the stream of words in a book trained the human brain into a habit of self-consciousness, that reading books forced human beings to think of themselves as a stream of text, processed through time, making a coherent argument of some sort. And that this overall flattening effect forced readers to ignore aspects of their personality or their situation that were not otherwise in line with the overarching story they'd created about themselves. Basically, reading books causes repression and neurosis. The Literacy Delusion argued that, yes, human beings are storytelling machines, but that a stream of written text is a particular kind of story—a story that is particularly flat, particularly devoid of conflicting or harmonizing information—and that this flatness creates a peculiar effect on the human brain. 51: Last month, I linked Sasha Gusev’s No, Intelligence Is Not Like Height and asked people who disagreed to share their arguments; they sure did. First, several people pointed me to a new preprint, Family-GWAS Reveals Effects Of Environment And Mating On Genetic Associations, which finds that one of the main papers Gusev cited to make his case, Howe 2022, made a mistake - imputing sibling genotypes using a process designed for non-sibling genotypes - and that once that mistake is corrected, the finding disappears and intelligence and height appear similar. Second, Joseph Bronski has a more specific post where he responds to Gusev’s points one by one. He accuses Gusev of “[making] up his own chart to remove the error bars [from the originals], to obscure the fact that the study found no evidence for this in IQ”, and says that the cases where he didn’t do that are just “population stratification and range restriction”. Third, Noah Carl at Aporia, instead of writing a direct response like Bronski, argues that the usual method of attacking twin studies is obsolete; not only have the most-debated assumptions behind twin studies been thoroughly validated, but there are now other lines of evidence besides twin studies which confirm high IQ heritability. Fourth, Leonardo Parro (not framed as a response to Gusev) goes into more depth about one of those ways, a “pedigree-based analysis” demonstrating heritability of 54 - 69%, ie no “missing heritability” compared to twin studies. He summarizes this as the effect of “rare variants” compared to the usual SNPs - ie if you only look at the most common genes that are easiest to find, you get “missing heritability” compared to twin studies, but if you widen your search to rare genes that are hard to find, you don’t. 52: Extremely related: Heliospect is a startup promising polygenic selection for IQ and other traits; they were trying to stay in stealth mode but The Guardian spied on them and nonconsensually revealed their existence. The discussion on the r/ssc subreddit centered on their claim that (given enough embryos to choose from) they could increase a baby’s expected IQ by 6 points (I’ve also heard 7.5). Sasha Gusev had previously argued that current technology maxed out at 3.5 and future technology would max out at 6, so a claim of 6 - 7.5 is pretty extreme; Gwern, who wrote the pioneering analysis of this technology, was also skeptical. But Heliospect says they’ve got better predictors than academia that use the rare variants everyone else misses; after talking to the company, Gwern retracted his objections and says he finds their claim “pretty plausible”. Local ACX commenter geneticist Gene Smith also redid some calculations, changed his mind, and says “probably pretty realistic”. I find this interesting not just because of the polygenic selection angle, but because if Heliospect is right then their predictor is able to predict more genetic IQ than the “missing heritability” people believe exists, and it should be able to put this argument to bed once and for all. 53: This month in censorship: X/Twitter banned journalist Ken Klippenstein for sharing the Trump campaign’s dossier on JD Vance. Twitter’s side of the story is that the dossier was probably originally stolen by Iranian agents and they don’t want to support that kind of thing by letting people signal-boost the illicitly obtained goods; you can read Klippenstein’s side here. He appears to be unbanned now.
Eli Lilly

Eli Lilly is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between May 18, 2022 and March 12, 2025. The archive places it in contexts such as "gotten money from Eli Lilly"; "Novo Nordisk’s competitor Eli Lilly owns a closely related molecule"; "Eli Lilly stock moons". It most often appears alongside United States, Eli Lilly, Elon Musk.

Article page
Eli Lilly
Mention count
4
Issue count
4
First seen
May 18, 2022
Last seen
March 12, 2025
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
November 24, 2022 · Original source
The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 05, 2024 · Original source
Yet in the end, everything is so perfectly balanced that the sum total of these luminaries refuse to say which side of even we’re on. The nation balances on a knife’s edge. Eli Lilly stock moons. A red sun hangs over Philadelphia, where American democracy began and may yet end. A man walks into a diner just before closing time. He looks like a good tipper. The waitress was hoping to leave early and go vote. She decides against. Seven trumpets sound; seven seals are opened; there is silence in Heaven for the space of about half an hour. As George RR Martin put it, “God flips a coin and the world holds its breath.” Tomorrow - if we are so lucky - there will be a result. The great function that has consumed us for so long will return 0 or 1. The pundits who guessed 51-49 will be hailed as prophets; the pundits who guessed 49-51 will get bullied out of public life. The winner’s campaign operatives will be praised as world-historic geniuses, the loser’s mocked forever as utter nincompoops. Thousands of lifelong public servants who backed Mr. 49% will be tossed from DC like used toilet paper and replaced with thousands of hacks who backed Mr. 51%. Funding streams will go dry. Whole lands will turn to economic deserts. Fortunes will be destroyed. A few people will make good on their exile and suicide threats. Most won’t. The Union will either survive or not. If it survives, we’ll do it all over again four years later. A red sun sets over DC. The marble monuments are stained crimson; the statues of Lincoln and Jefferson and the rest look like they writhe in hellfire. The people seclude themselves in their houses. A city where even the Christians are atheist kneels in prayer. On some level, they know - we know - it was never just about choosing a leader. It was all for this - the same urge that drove the games of the Colosseum and sacrifices of Tenochtitlan. The need for a single moment of unconditioned reality. For one evening, the people of the richest and most secure nation in history, fat off the spoils of six continents, will know the same fear as the starving Catalhuyuk farmer, staring at the sky, wondering if the rains will come. For one evening, everyone - rich or poor, religious or secular, Democrat or Republican - will join in the prayer of the poet: “Judge of the Nations, spare us yet Lest we forget - lest we forget!” Don’t Blame Me, I Voted For Kodos Metaculus uses experimental “conditional forecasts” to determine the consequences of a Trump/Harris victory. How it works (example): you set up two forecasts: If Trump wins, will China invade Taiwan?
March 12, 2025 · Original source
But the compounders aren’t the only ones boxing clever. Novo Nordisk and Eli Lilly, the pharma companies behind semaglutide and tirzepatide respectively, have opened consumer-facing businesses about halfway between a traditional doctor’s appointment and the telehealth/compounder model that’s getting banned. So for example, Lilly Direct offers to “find you a doctor” (I think this means you do telehealth with an Eli Lilly stooge who always gives you the meds you want) and “get medications delivered directly to you”. The price depends on dose, but an average dose would be about $500 - so about halfway between the cheap compounding price and the usual insurance price. Not bad.
Pharma companies don’t like dose-based pricing (that is, charging twice as much for a 10 mg dose as a 5 mg dose). Part of their objection is ethical - some people have unusual genes that make them need higher doses, and it seems unfair to charge these people twice as much for genetic bad luck. But there’s also an economic objection - they want to charge the maximum amount the customer can bear, but if they charge a subset of people with genetic bad luck twice as much as they can bear, those people won’t buy their drug. So usually they sell all doses at a similar price, opening an arbitrage opportunity: if they sell both 5 mg and 10 mg for $500/month, and you need 5 mg, then buy the 10 mg dose, take half of it at a time, stretch out your monthlong supply for two months, and get an effective cost of $250/month. But here Eli Lilly is doing something devious I’ve never seen before. They’re selling their medication in single-dose vials, deliberately without preservatives, so that you need to take the whole dose immediately as soon as you open the vial - the arbitrage won’t work! So although this looks on paper like a $300 price increase ($200 to $500), the increase will be even higher for people who were previously exploiting the dose arbitrage.
Gamestop

Gamestop is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between February 01, 2021 and December 20, 2022. The archive places it in contexts such as "you can still buy all the Gamestop stock you want"; "Gamestop stock price still above $100"; "Meme stocks like Gamestop and AMC sometimes remain mispriced indefinitely". It most often appears alongside Ethereum, PredictIt, COVID.

Article page
Gamestop
Mention count
4
Issue count
4
First seen
February 01, 2021
Last seen
December 20, 2022
February 01, 2021 · Original source
But they're not quite the present. Right now I only know of three prediction markets, and none of them live up to their potential. As usual, it’s the government’s fault: betting on prediction markets is technically gambling, which makes it mostly illegal (of course, you can still buy all the Gamestop stock you want).
April 26, 2021 · Original source
ECON/TECH 14. Gamestop stock price still above $100: 50% 15. Bitcoin above 100K: 40% 16. Ethereum above 5K: 50% 17. Ethereum above 0.05 BTC: 70% 18. Dow above 35K: 90% 19. ...above 37.5K: 70% 20. Unemployment above 5%: 40% 21. Google widely allows remote work, no questions asked: 20% 22. Starship reaches orbit: 60%
February 01, 2022 · Original source
ECON/TECH 11. Gamestop stock price still above $100: 30% 12. Bitcoin above 100K: 20% 13. Ethereum above 5K: 20% 14. Ethereum above 0.05 BTC: 90% 15. Bored Ape floor price here below current price of $203K: 40% 16. Dow above 35K: 90% 17. ...above 37.5K: 40% 18. Inflation for the year below five percent: 90% 19. Unemployment below five percent: 50% 20. Google widely allows remote work, no questions asked: 50% 21. Starship reaches orbit: 90%
December 20, 2022 · Original source
Able to get top-1 strict accuracy of at least 90.0% on interview-level problems found in the APPS benchmark introduced by Dan Hendrycks, Steven Basart et al. Top-1 accuracy is distinguished, as in the paper, from top-k accuracy in which k outputs from the model are generated, and the best output is selected. By "unified" we mean that the system is integrated enough that it can, for example, explain its reasoning on a Q&A task, or verbally report its progress and identify objects during model assembly. (This is not really meant to be an additional capability of "introspection" so much as a provision that the system not simply be cobbled together as a set of sub-systems specialized to tasks like the above, but rather a single system applicable to many problems.) Resolution will come from any of three forms, whichever comes first: (1) direct demonstration of such a system achieving ALL of the above criteria, (2) confident credible statement by its developers that an existing system is able to satisfy these criteria, or (3) judgement by a majority vote in a special committee composed of the question author and two AI experts chosen in good faith by him, for the sole purpose of resolving this question. Resolution date will be the first date at which the system (subsequently judged to satisfy the criteria) and its capabilities are publicly described in a talk, press release, paper, or other report available to the general public. Even this isn’t perfect (which models are “the equivalent of” a 1:8 scale Ferrari 312?), but in practice once you get to this level of details people mostly stop worrying about this. Another method (mostly associated with Manifold) is to just leave it up to human judgment - specifically, the judgment of the person who made the market. For example, I could make a market in “By 2050, will there be an AI which Scott Alexander thinks qualifies as ‘human-level’?” This will force market participants to price in the risk that I have bad judgment or act dishonestly. But perhaps these risks are small. For example, I might say elsewhere what I think qualifies as “human-level” AI, or you might think human-level AI will be so obvious when it comes that I will definitely agree with you about it. As for honesty, this could be enforced either legally or by reputation. Someone who has resolved their past 100 prediction markets honestly will probably resolve this one honestly too, especially if they get paid to do so and will never get customers again if they lie. When we invest on the normal stock market, we trust that our brokers / the NYSE / etc won’t run off with our money, and this trust is usually well-deserved. Even when we make an online purchase, we trust that the store we’re sending our money to won’t steal it and refuse to send us the product. It would be an exaggeration to say that trust is a solved problem, but evidence from Manifold suggests that most people price in a <1% chance that well-known market makers with good reputation resolve dishonestly. If prediction markets got big enough, they could spawn trusted “resolution companies” who individual markets and market-makers could outsource their resolution to, for a fee. If these companies were ever dishonest, they would lose all their business from then on, so they would probably be as honest as other businesses like your broker / the NYSE / various online stores / etc. 4.7.1: Isn’t a lot of the “crisis of trust” around questions that might never have clear future answers? For example, consider the debate around whether Donald Trump is a Russian agent. Maybe no proof will ever come out either way. Or maybe some evidence will appear that seems to prove one side or the other, but people will continue to deny it for political reasons, and the problem of resolving the prediction market will be just as hard as the problem of answering the original question. Indeed, prediction markets aren’t very good at this, and are only fully trustworthy on questions where the true answer will eventually become apparent. Still, they might not be completely useless. For example, if you’re worried about Trump being a Russian agent because you expect him to pursue pro-Russia policies, you can start markets in whether he pursues those policies. Or you can start a conditional market (see 5.1) on whether, if Russia ever releases its past intelligence data many years from now, the data confirm/disconfirm that Trump was an agent. See Part 5 for other clever ways you might try to address this problem. 4.8: “Meme stocks” like Gamestop and AMC sometimes remain mispriced indefinitely. How do we know this won’t happen with prediction markets? Meme stocks are a type of Ponzi. It’s “reasonable” to buy Gamestop at some inflated price, because - who knows? - someone else might buy it at an even more inflated price tomorrow. And this can keep going arbitrarily long, or at least long enough for you to get out with a profit. Unlike meme stocks, prediction markets have a clear resolution date. If you’re predicting who will win the next election, the market will go to 100% or 0% after the election finishes. No matter how many memes there were, you wouldn’t buy a share in “the Democrats will win the election” for 99% the day before Election Day if you knew they would definitely lose. But that means prediction markets should be accurately priced the day before Election Day, which means you shouldn’t buy at an inaccurate price two days before Election Day, and so on. I can’t say for sure that no prediction market will ever get mispriced for meme reasons, but they should be much more robust against meme mispricings than the stock market. And even the stock market doesn’t have too many meme stocks. 4.9: How do prediction markets deal with outcomes in the far future? Suppose there is a question “who will win the 2100 election?” Currently it says 25% Democrats, 75% Republicans, and I believe it should be 50-50 (we’ll ignore third parties, or the possibility of America not existing in 2100, for now). So if I bet on the market, I can (in expectation) double my money. But there are many better ways to double your money by 2100. For example, if the stock market grows 4% per year, I should expect any money invested in the stock market to multiply by 20x in 2100. So just doubling it in a prediction market is a bad option. Realistically, this means prediction markets won’t work well for far-future events. These might be a better match for forecaster tournaments or some other structure, where we get the forecaster track records through present events, then use those track records weighting their far-future predictions (see also 5.5). There are already good forecasting tournaments on some far future events. But if you really wanted to use a prediction market, you could theoretically solve this by putting investors’ money in index funds while they waited. Then the winner would get their (and the losers’) original deposits and investment profits, and it would go back to being a better option than investing in index funds directly. In practice this seems complicated and I wouldn’t expect it to work. 4.9.1: What about predicting things that would make it impossible or pointless to win money, like human extinction? Again, these questions probably aren’t great matches for prediction markets, and you should use forecasting tournaments or some other method (see also 5.5). If you really wanted, you might be able to make it work in theory through a mechanism sort of like this one. 5. What are some clever uses for prediction markets? Here’s a non-exhaustive list: 5.1: Conditional prediction markets / decision markets Suppose the government is trying to decide whether to throw its weight behind Vaccine A or Vaccine B for some deadly disease. There are some experts behind both, both sets of experts accuse the other of being in the pay of pharmaceutical companies, and decision-makers don’t know who to trust. They might make two prediction markets, like: If we decide to go with Vaccine A, will at least X people die from the disease?
GPT-2

GPT-2 is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between April 11, 2022 and March 14, 2023. The archive places it in contexts such as "After GPT-2, DALL-E, and the rest"; "Now it is true that GPT-3 is genuinely better than GPT-2"; "A few years ago I wrote about attempts to make GPT-2 play chess". It most often appears alongside Eliezer Yudkowsky, DALL-E, GPT.

Article page
GPT-2
Mention count
4
Issue count
4
First seen
April 11, 2022
Last seen
March 14, 2023
April 11, 2022 · Original source
Prosaic alignment is hard… “Prosaic alignment” (see this article for more) means alignment of normal AIs like the ones we use today. For a while, people thought those AIs couldn’t reach dangerous levels, and that AIs that reached dangerous levels would have so many exotic new discoveries that we couldn’t even begin to speculate on what they would be like or how to align them. After GPT-2, DALL-E, and the rest, alignment researchers got more concerned that AIs kind of like current models could be dangerous. Prosaic alignment - trying to align AIs like the ones we have now - has become the dominant (though not unchallenged) paradigm in alignment research. “Prosaic” doesn’t necessarily mean the AI cannot write poetry; see Gwern’s AI generated poetry for examples. … because OOD behavior is unpredictable “OOD” stands for “out of distribution”. All AIs are trained in a certain environment. Then they get deployed in some other environment. If it’s like the training environment, presumably their training is pretty relevant and helpful. If it’s not like the training environment, anything can happen. Returning to our stock example, the “training environment” where evolution designed humans didn’t involve contraceptives. In that environment, the base optimizer’s goal (pass on genes) and the mesa-optimizer’s goal (get genital friction) were very well-aligned - doing one often led to the other - so there wasn’t much pressure on evolution to look for a better proxy. Then 1957, boom, the FDA approves the oral contraceptive pill, and suddenly the deployment environment looks really really different from the training environment and the proxy collapses so humiliatingly that people start doing crazy things like electing Viktor Orban prime minister. So: suppose we train a robot to pick strawberries. We let it flail around in a strawberry patch, and reinforce it whenever strawberries end up in a bucket. Eventually it learns to pick strawberries very well indeed. But maybe all the training was done on a sunny day. And maybe what it actually learned was to identify the metal bucket by the way it gleamed in the sunlight. Later we ask it to pick strawberries in the evening, where a local streetlight is the brightest thing around, and it throws the strawberries at the streetlight instead. So fine. We train it in a variety of different lighting conditions, until we’re sure that, no matter what the lighting situation, the strawberries go in the bucket. Then one day someone with a big bulbous red nose wanders on to the field, and the robot tears his nose off and pulls it into the bucket. If only there had been someone with a nose that big and red in the training distribution, so we could have told it not to do that! The point is, just because it’s learned “strawberries into bucket” in one environment, doesn’t mean it’s safe or effective in another. And we can never be sure we’ve caught all the ways the environment can vary. …and deception is more dangerous than Goodharting. To “Goodhart” is to take advantage of Goodhart’s Law: to follow the letter of your reward function, rather than the spirit. The ordinary-life equivalent is “teaching to the test”. The system’s programmers (eg the Department of Education) have an objective (children should learn). They delegate that objective to mesa-optimizers (the teachers) via a proxy objective (children should do well on the standardized test) and a correlated reward function (teachers get paid more if their students get higher test scores). The teachers can either pursue the base objective for less reward (teach children useful skills), or pursue their mesa-level objective for more reward (teach them how to do well on the test). An alignment failure! This sucks, but it’s a bounded problem. We already know that some teachers teach to the test, and the Department of Education has accepted this as a reasonable cost of having the incentive system at all. We might imagine our strawberry-picker cutting strawberries into little pieces, so that it counts as having picked more strawberries. Again, it sucks, but once a programmer notices it can be fixed pretty quickly (as long as the AI is still weak and under control). What about deception? Suppose the strawberry-picker happens to land on some goal function other than the intended one. Maybe, as before, it wants to toss strawberries at light sources, in a way that works when the nearest light source is a metal bucket, but fails when it’s a streetlight. Our programmers are (somewhat) smart and careful, so during training, they test it at night, next to a streetlight. What happens? If it’s just a dumb collection of reflexes trained by gradient descent, it throws the strawberry at the streetlight and this is easily caught and fixed. If it’s a very smart mesa-optimizer, it might think “If I throw the strawberry at the streetlight, I will be caught and trained to have different goals. This totally fails to achieve my goal of having strawberries near light sources. So throwing the strawberry at the light source this time, in the training environment, fails to achieve my overall goal of having strawberries thrown at light sources in general. I’ll do what the humans want - put the strawberry in the bucket - for now.” So it puts the strawberry in the bucket and doesn’t get caught. Then, as soon as the humans stop looking, it throws strawberries at the streetlight again. Deception is more dangerous than Goodharting because Goodharting will get caught and trained away, and deception might not. I might not be explaining this well, see also Deceptively Aligned Mesa-Optimizers? It’s More Likely Than You Think: We prevent OOD behavior by detecting OOD and obtaining more human labels when we detect it… If you’re (somewhat) careful, you can run your strawberry-picking AI at night, see it throw strawberries at streetlights, and train it out of this behavior (ie have a human programmer label it “bad” so the AI gradient-descends away from it) …and we eliminate the incentive for deception by ensuring that the base optimizer is myopic A myopic optimizer is one that reinforces programs based only on their performance within a short time horizon. So for example, the outside gradient descent loop might grade a strawberry picker only on how well it did picking strawberries for the first hour it was deployed. If this worked perfectly, it would create an optimizer with a short time horizon. When it considered deceiving its programmers in order to get a payoff a few days later when they stopped watching it, it wouldn’t bother, since a few days later is outside the time horizon. …and implements a decision theory incapable of acausal trade. You don’t want to know about this one, really. Just pretend it never mentioned this, sorry for the inconvenience. There are deceptively-aligned non-myopic mesa-optimizers even for a myopic base objective. Even if the base optimizer is myopic, the mesa-optimizer might not be. Evolution designed humans myopically, in the sense that we live some number of years, and nothing that happens after that can reward or punish us further. But we still “build for posterity” anyway, presumably as a spandrel of having working planning software at all. Infinite optimization power might be able to evolve this out of us, but infinite optimization power could do lots of stuff, and real evolution remains stubbornly finite. Maybe it would be helpful if we could make the mesa-optimizer itself myopic (though this would severely limit its utility). But so far there is no way to make a mesa-optimizer anything. You just run the gradient descent and cross your fingers. The most likely outcome: you run myopic gradient descent to create a strawberry picker. It creates a mesa-optimizer with some kind of proxy goal which corresponds very well to strawberry picking in the training optimization, like flinging red things at lights (realistically it will be weirder and more exotic than this). The mesa-optimizer is not incentivized to think about anything more than an hour out, but does so anyway, for the same reason I’m not incentivized to speculate about the far future but I’m doing so anyway. While speculating about the far future, it realizes that failing to pick strawberries correctly now will thwart its goal of throwing red things at light sources later. It picks strawberries correctly in the training distribution, and then, when training is over and nobody is watching, throws strawberries at streetlights. (Then it realizes it could throw lots more red things at light sources if it was more powerful, achieves superintelligence somehow, and converts the mass of the Earth into red things it can throw at the sun. The end.) III. You’re still here? But we already finished explaining the meme! Okay, fine. Is any of this relevant to the real world? As far as we know, there are no existing full mesa-optimizers. AlphaGo is kind of a mesa-optimizer. You could approximate it as a gradient descent loop creating a good-Go-move optimizer. But this would only be an approximation: DeepMind hard-coded some parts of AlphaGo, then gradient-descended other parts. Its objective function is “win games of Go”, which is hard-coded and pretty clear. Whether or not you choose to call it a mesa-optimizer, it’s not a very scary one. Will we get scary mesa-optimizers in the future? This ties into one of the longest-running debates in AI alignment - see eg my review of Reframing Superintelligence, or the Eliezer Yudkowsky/Richard Ngo dialogue. Optimists say: “Since a goal-seeking AI might kill everyone, I would simply not create one”. They speculate about mechanical/instinctual superintelligences that would be comparatively easy to align, and might help us figure out how to deal with their scarier cousins. But the mesa-optimizer literature argues: we have limited to no control over what kind of AIs we get. We can hope and pray for mechanical instinctual AIs all we want. We can avoid specifically designing goal-seeking AIs. But really, all we’re doing here is setting up a gradient descent loop and pressing ‘go’. Then the loop evolves whatever kind of AI best minimizes our loss function. Will that be a mesa-optimizer? Well, I benefit from considering my actions and then choosing the one that best achieves my goal. Do you benefit from this? It sure does seem like this helps in a broad class of situations. So it would be surprising if planning agents weren’t an effective AI design. And if they are, we should expect gradient descent to stumble across them eventually. This is the scenario that a lot of AI alignment research focuses on. When we create the first true planning agent - on purpose or by accident - the process will probably start with us running a gradient descent loop with some objective function. That will produce a mesa-optimizer with some other, potentially different, objective function. Making sure you actually like the objective function that you gave the original gradient descent loop on purpose is called outer alignment. Carrying that objective function over to the mesa-optimizer you actually get is called inner alignment. Outer alignment problems tend to sound like Sorcerer’s Apprentice. We tell the AI to pick strawberries, but we forgot to include caveats and stop signals. The AI becomes superintelligent and converts the whole world into strawberries so it can pick as many as possible. Inner alignment problems tend to sound like the AI tiling the universe with some crazy thing which, to humans, might not look like picking strawberries at all, even though in the AI’s exotic ontology it served as some useful proxy for strawberries in the training distribution. My stand-in for this is “converts the whole world into red things and throws them into the sun”, but whatever the AI that kills us really does will probably be weirder than that. They’re not ironic Sorcerer’s Apprentice-style comeuppance. They’re just “what?” If you wrote a book about a wizard who created a strawberry-picking golem, and it converted the entire earth into ferrous microspheres and hurled them into the sun, it wouldn’t become iconic the way Sorcerer’s Apprentice did. Inner alignment problems happen “first”, so we won’t even make it to the good-story outer alignment kind unless we solve a lot of issues we don’t currently know how to solve. For more information, you can read: Rob Miles’ video above, direct link here, channel here.
June 10, 2022 · Original source
Now it is true that GPT-3 is genuinely better than GPT-2, and maybe (but maybe not, see footnote 1) true that InstructGPT is genuinely better than GPT-3. I do think that for any given example, the probability of a correct answer has gone up. [Scott] is quite right about that, at least for GPT-2 to GPT-3.
Literally billions of dollars have been invested in building systems like GPT-2, and megawatts of energy (perhaps more) have gone into testing them; few systems if any have ever been trained on bigger data sets. Many of the brightest minds have been working on blank-slate-ish sentence prediction systems for decades.
In essence, GPT-2 has been a monumental experiment in Locke's hypothesis, and so far it has failed. Empiricism has been given every advantage in the world; thus far it hasn't worked. Even with massive data sets and enormous compute, the knowledge that it acquires has been superficial and unreliable.
March 10, 2023 · Original source
11: A few years ago I wrote about attempts to make GPT-2 play chess; it couldn’t consistently make legal moves, but when it did, its moves seemed better than random although still not great. Zack Witten reports playing chess with Bing (either a late GPT-3 or an early GPT-4) and finds it’s much better - he reports consistently legal play with Elo of about 1100 (around the level of an okay beginner who’s stopped being too embarrassing). Other commenters report worse experiences and more illegal moves; I don’t have access to confirm.
March 14, 2023 · Original source
5: Will takeoff be slow vs. fast? So far we’ve had brisk but still gradual progress in AI; GPT-3 is better than GPT-2, and GPT-4 will probably be better still. Every few years we get a new model which is better than previous models by some predictable amount.
ibuprofen

ibuprofen is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between April 13, 2022 and August 13, 2024. The archive places it in contexts such as "mothers who took the alternate headache medication ibuprofen did not have kids with more ADHD"; "Ibuprofen ("Advil", "Motrin") has effect sizes"; "Ibuprofen helps arthritis pain". It most often appears alongside Leucht et al, acetaminophen, ACX survey.

Article page
ibuprofen
Mention count
4
Issue count
4
First seen
April 13, 2022
Last seen
August 13, 2024
April 13, 2022 · Original source
Doctors have been gradually chipping away at pregnant women’s ability to use pain medication. First it was “don’t use opioids, your baby could have birth defects”. Then it was “and don’t use ibuprofen, your baby could have kidney problems”. Then it was “and don’t use too much aspirin either, your baby could get cardiovascular problems”. That left Tylenol (aka Panadol, paracetamol, acetaminophen, etc) as the only pregnancy-safe pain reliever. Well, bad news…
ADHD is very genetic, so we should be alert for possible confounders like “ADHD moms get more stressed, have more headaches, and so use more Tylenol, and then their kids inherit their ADHD”. But we have two signs that this isn’t what’s going on here. First, a (relatively weak) finding that mothers who took the alternate headache medication ibuprofen did not have kids with more ADHD. And second, two studies (1, 2) finding that taking Tylenol immediately after or immediately before pregnancy has no effect - if it was just a proxy for class or ADHD you’d expect the same correlation regardless of the woman’s pregnancy status. All of this makes the effect look real.
But remember: all the other painkillers, eg ibuprofen, are even worse. So what if you have pain during pregnancy?
May 31, 2023 · Original source
This doesn’t even include some of my favorites. Zolpidem (“Ambien”) has effect size around 0.39 for getting you to sleep faster. Ibuprofen (“Advil”, “Motrin”) has effect sizes between from about 0.20 (for surgical pain) to 0.42 (for arthritis). All of these are around the 0.30 effect size of antidepressants. There’s no anti-ibuprofen lobby trying to rile people up about NSAIDs, so nobody’s pointed out that this is “clinically insignificant”. But by traditional standards, it is!
June 08, 2023 · Original source
Ibuprofen helps arthritis pain: 0.42
August 13, 2024 · Original source
Most of the relevant papers say the drugs work by preventing inflammation. This is a catch-all term for the immune response to microbes; although it helps fight the microbes, it’s slightly toxic to the rest of the body and generally bad unless you’re actively fighting an infection. In chronic inflammation, ie the thing most of us with modern diets have all the time, general bad health damages the body, the immune system mistakes the damage for a microbial infection, and it provokes a constant low-grade inflammatory response. This is bad, so (if you’re not fighting an infection) anti-inflammatories are generally pretty useful. There are lots of anti-inflammatory drugs (aspirin is one, ibuprofen is another), but inflammation is a multifaceted process and no one drug can stop it entirely.
iPhone

iPhone is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between April 03, 2023 and September 19, 2025. The archive places it in contexts such as "That’s 1 year after the very first iPhone"; "world leaders - iPhones, 747s, GPTs - are mostly still designed in the US"; "one of the tools which lets you build native apps for iPhone and Android". It most often appears alongside Bill Gates, Congress, Deng Xiaoping.

Article page
iPhone
Mention count
4
Issue count
4
First seen
April 03, 2023
Last seen
September 19, 2025
April 03, 2023 · Original source
If for some reason that doesn’t work, go to a different psychiatrist and try again. You don’t have to tell them you already tried. Since everything about ADHD diagnosis and treatment is already security theater, it’s hard to say what pill mills are doing except kind of smirking under their breath while going through the rituals - as opposed to real doctors, who go through the rituals with sincere faith. Don’t get me wrong, I do think there’s a difference here. But the regulatory state isn’t set up to say “And you have to sincerely believe in the rituals or they don’t count”. So instead they punish unrelated groups, like telepsychiatrists. See also my old post Bureaucracy As Active Ingredient. The security theater doesn’t work because it’s effective. It works because it’s inconvenient enough to weed out the less motivated fakers, and some of the remaining fakers get cold feet about lying to a nice sincere psychiatrist who seems to be trying to help them. Pill mills remove the inconvenience, and seem to be nod-and-wink cooperating with liars, so the theater stops working. The only solution is to inject some inconvenience and shame back into the process somewhere, which the DEA has chosen to do by restricting telepsychiatry. They could accomplish the same goal by making you attend your appointments naked, but I guess clothing companies have better lobbyists than telepsychiatrists do. 4: Comments About Forcing Blind People To Fill Out Forms Before They Can Access Braille I analogized forcing patients to see an in-person doctor before they could access a teledoctor to forcing blind people to fill out forms before they could access Braille. Several blind people and their friends pitched in to say this was a real problem. For example, Mikolysz: Blind person here, this kind of thing is actually much more common than people imagine. Many government agencies (regardless of which particular government you mean) just assume that anybody who needs to fill a form can read and write print and/or lives with somebody who does. This is often a problem even when the form in question is specifically targeted at blind people. Non-governmental organizations, including those who specifically serve the blind, aren't much better at this either. This issue is slightly more pronounced in civil law countries, where what constitutes a legally-binding signature is clearly defined in law and you can't just Docusign your way out of the problem, but it exists everywhere, including the US. I literally had to file this kind of document today, while the main form could be filled electronically, I was required to attach a few extra documents, for GDPR and such, and those had to be printed, filled in by a sighted person, signed and scanned. The same problem exists with physical mail which you're required to read and respond to, but which is almost never available in an accessible form, a few exceptions like the American IRS notwithstanding. 5: Comments About My Caricature Of A Doctor Who Refuses To Prescribe Psych Drugs Because People Just Need Jesus Jon Cutchins writes: You don't want psychiatrists and liberals in general to be accused of an unreasoning hatred towards Christianity you should probably be more judicious in your use of anti-Christian tropes when describing everyone who is skeptical of mind-altering drugs. Mike writes: I’ve been a primary care nurse practitioner in the Bible Belt for 20yrs and not once have I even heard of a provider telling a patient they should substitute religion for psychiatric (or any) medication. It’s so easy for some people to throw around these tropes as if Christianity is some exotic, weird tribe with horrifying anthropological traits. On the other hand, fluxe writes: I am a young Christian--in my life, I have -been told by my PCP not to get an IUD because it carries "a significant risk of causing infertility or death" -had a pharmacist refuse to fill an old, male family friend's ulcer medication because it's also an abortifacient -been told by a therapist to discontinue the SSRI a different provider had prescribed and just trust in the man of the house the PCP wasn't even particularly Christian herself, but since all of her patients are she hadn't updated on IUDs since the scare back in the 70s. Our horrifying anthropological traits become everyone's problem--it might be worth listening to those who "throw around these tropes" so you can understand what they have to deal with Unfortunately I only mention this possibility because it’s happened to several of my patients. The best I can offer in terms of being unbiased and apolitical is to signal-boost posts like this one about overly woke therapists being another big problem. Alien on Earth writes: I generally like your writing and ideas, hell, I just re-uped for a year. However, in an otherwise near perfect post, you took a cheap shot at a steriotyped view of one religion thst is not popular amoungst coastal elites, that really detracts from your core point. "The worst-case is that you get one of those doctors who think that Psych Drugs Aren’t Real Because You Just Need Jesus, and then the patient has to keep looking until they find someone else." In my experience, it is the new age(y), non-religious, doctors who are least likely to like prescribing psyc. meds or who tend to give them at too low a dose or for too short a time. Certainly, I've found little correlation with their religion, if I even know it. The only correlation I've observed is that this perscription reluctance is, perhaps, slightly more common amongst middle career doctors. Perhaps it is more common in deep red areas, I don't know. However, even there, I would suggest, it is less due to religion, per se, than to "old fashion" "grit your teeth and bear it" thinking. I agree that there are many reasons people recommend against psychiatric drugs (a few are even good). Psychiatric drugs have lots of side effects and are clearly imperfect options, and I see people object to them more often when they think they have a perfect option as an alternative. Sometimes that option is Jesus. Other times it’s the trendy new somatic yoga reprocessing kundalini trauma dianetics therapy. Other times it’s LSD or ketamine or Dr. Bob’s 24-In-One Internet Nootropic. All of these work for some people, but not as much as the people pushing them think - which I guess is also true for psych drugs. I’m nervous about people who think they’ve found the answer and pressure people towards one alternative or another without presenting evidence. I’ve seen this happen enough in religious contexts that I think it was a fair thing to use as an example. 6: Comments About Which Part Of The Government Is Responsible For This Regulation ProfessorE writes: I’m not sure that what Scott wrote is even completely accurate. I have a relative who is an MD in this space, and it seems that the underlying problem is not the DEA but an actual law passed by Congress. Aren’t telemedicine regulations limited with respect to controlled substances by the Ryan Haight Act of 2008 U.S.C. § 829(e)… there may be interpretations of this act by the DEA and other agencies, but, where controlled substances are prescribed by means of the Internet, the general requirement is that the prescribing Practitioner must have conducted at least one in-person medical evaluation of the patient. It seems like a colossal overreach to ask an Executive Branch agency to overrule the plain text of the act. There are some exceptions, which Scott noted. A different way of looking at things was that the Executive Branch was highly responsive to the emergency situation of Covid. Now that it’s not an emergency, they are obligated to return to the legal framework that exists. Congress needs to change the law, not the DEA. The *data* from covid should be used as part of a cost-benefit analysis to determine whether it is reasonable to regulate telemedicine, and, if so, what regulations might address whatever problems arose. Followed by: Actually, Scott is even more off-base than I thought in my initial post. Apparently the DEA & DOJ are already proposing new changes to the 2008 Act (which seem like they violate the clear text of the act), but the act and the changes are summarized here: https://www.legitscript.com/2023/03/27/proposed-changes-ryan-haight/ Sounds like government is aware of the issue. See https://www.federalregister.gov/documents/2023/03/01/2023-04248/telemedicine-prescribing-of-controlled-substances-when-the-practitioner-and-the-patient-have-not-had For the actual changes that are being proposed. End of the day, this should be modified by Congress, not the agencies. Everyone should remember that the law was written in 2008. That’s 1 year after the very first iPhone and 2 years before the first iPad. Zoom didn’t exist (2011). None of the other technologies for video conferencing existed. Congress was attempting to fight opioid pill-mills. At the time of passage, I am willing to bet that ≈0% of patients were “Telehealth” using videoconferencing. More like phone calls and email a few times to get drugs. The law should have been amended, and it hasn’t been, but it is far from clear that it was a crazy law in the first place. I mostly accept this correction, although I’m still a bit confused - a lot of the analyses by lawyers I read said things like “Unquestionably, the DEA’s proposal is not what most industry stakeholders were anticipating. The initial reaction is the rules are more restrictive than necessary and impose concerning limitations and burdens on clinicians and the patients they treat”, and I’m confused why industry stakeholders weren’t anticipating it if the DEA had to do it in order to follow the law. And JR writes: Meanwhile, the DEA was instructed by law in -2008- to develop a special registration process for telemedicine to allow providers to prescribe controlled substances remotely. The DEA has simply failed to do so in that time, despite repeated Congressional demands to act. Don't worry, though - the DEA has said about this proposed rule that it feels this will be 'less burdensome' for providers than any kind of special registration, so it feels it has discharged its legal responsibility to create a special registration process. I am a psychiatrist having to deal with this idiocy with my patients too, and renting an office temporarily is not going to cut it. So I am going the letter route. I will probably a lose a reasonable chunk of patients I was prescribing controlled substances to. The only possible saving grace is that PCPs in this country are used to being asked to sign and complete all kinds of nonsense forms and documents so probably most of them will just do it with minimal fuss. I'm more concerned with the new requirement that all telemedicine scripts now have to be recorded by the prescriber with the date and time they were written, the PHYSICAL ADDRESS of the prescriber and patient at the time of the telehealth encounter, and have an explicit note on them that they are telemedicine prescriptions. I am less concerned about PCPs balking at writing an idiotic referral than I am skittish pharmacists refusing to fill scripts that they might interpret as being labeled equivalently to FAKE SCRIPT FOR DRUGSEEKERS Based on that comment and this, my best guess about what’s happening is: Congress passed restrictions on telemedicine in 2001, and asked the DEA to come up with a way that trusted providers could avoid those restrictions. Now that there is videoconferencing, etc, most people now believe those restrictions were too severe.
June 07, 2023 · Original source
So far. China hasn’t quite caught up to America. Their GDP per capita is still less than a quarter of ours. Although they make many excellent products, the world leaders - iPhones, 747s, GPTs - are mostly still designed in the US, even if Chinese factories churn out the parts. Other Asian tigers like South Korea and Taiwan liberalized politically around the point where they started approaching developed-country GDP; in his analysis of their rise, Joe Studwell suggests that this might have been a necessary component. And Japan, despite all the virtues that made Wang think they would overtake the US, has stagnated instead.
November 10, 2023 · Original source
This is a pure-front-end-web-app with all the sentences hard-coded. I don't see any issue with getting accurate timing: the timing could be done client side (as others have said) and I really think even a web-app like this would be high-fidelity enough for human-scale interactions. The only issue is security. I don't think you could make a web-app that's secure against someone cheating if they really wanted to. If we're measuring biases people might be trying to hide, this would be an issue. The solution would be to make a native app of some sort. I'd probably use one of the tools which lets you build native apps for iPhone and Android.
September 19, 2025 · Original source
It’s on Youtube; I think you should watch it. When I was younger, my dad had me watch Steve Jobs’ iPhone presentation; held it up as a prime example of tech and sales, innovation and elegance all rolled up. I liked it at the time. Now, having watched Engelbart’s presentation, I recognize it for what it is: patronizing, mass-market garbage. It’s just nowhere near as cool.
Lexapro

Lexapro is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between March 31, 2021 and October 27, 2023. The archive places it in contexts such as "What is the right dose of Lexapro (escitalopram)?"; "The first reason Lexapro might work so well despite its low dose"; "The second reason Lexapro might work so well". It most often appears alongside FDA, Ashwagandha, Ayurvedic.

Article page
Lexapro
Mention count
4
Issue count
4
First seen
March 31, 2021
Last seen
October 27, 2023
March 31, 2021 · Original source
What is the right dose of Lexapro (escitalopram)?
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
Because Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram). Sometime around 2011, the FDA freaked out that high doses of citalopram might cause a deadly heart condition called torsade de pointes, and lowered the maximum dose to prevent this. Since then it's been pretty conclusively shown that the FDA was mostly wrong about this and kind of bungled the whole process. But they forgot to ever unbungle it, so citalopram still has a lower maximum dose than every other antidepressant. When escitalopram was invented, it inherited its parent chemical's unusually-low maximum dose, and remains at that level today [edit: I got the timing messed up, see here]
October 05, 2022 · Original source
But zooming out: what is the proper dose of the antidepressant Lexapro? Trick question - it depends on the person - I have seen people need anywhere between 2.5 and 30 mg of it. So how do I prescribe it to someone? I usually tell them to start at 5 mg, then go up or down depending on whether it seems to be working, causing side effects, etc. A lot of herbal supplements are similar. If this is your strategy, a 25% labeling error isn’t going to matter much, is it? If my patients get their Lexapro from a sketchy company that actually has only 4 mg in a 5 mg pill, they’re still going to go up to 20 mg or down to 2 mg or whatever it is the end up needing, based on how it affects them. It will cause problems if they ever change brands, but probably not very many problems. And all of these substances have a wide enough therapeutic index that you’re not going to get toxicity from a 25% mislabeling. So although it’s correct for the industry to obsess over getting this right for purposes of honesty and reputation, as a consumer I don’t personally worry about it as much except for rare substances where specific doses are constant between people and make a big difference, or where you’re not supposed to feel anything (eg decreases heart attack risk over ten years) and so you can’t titrate the dose to effects. If it’s just something that’s supposed to make you less anxious, check how anxious you get!
October 26, 2022 · Original source
> "A lot of herbal supplements are similar. If this is your strategy, a 25% labeling error isn’t going to matter much, is it? If my patients get their Lexapro from a sketchy company that actually has only 4 mg in a 5 mg pill, they’re still going to go up to 20 mg or down to 2 mg or whatever it is the end up needing, based on how it affects them."
October 27, 2023 · Original source
This isn’t controlling for selection bias - but neither was my uncle’s anecdotal observation. So although it does make me slightly nervous, I’m not going to treat it as actionable evidence. Still, my girlfriend ending up begging me not to donate, and I caved. But we broke up in 2019. The next few years were bumpy, but by 2022 my life was in a more stable place and I started thinking about kidneys again. By then I was married. I discussed the risks with my wife and she decided to let me go ahead. So in early November 2022, for the second time, I sent a form to the University of California San Francisco Medical Center saying I wanted to donate a kidney. IV. Something else happened that month. On November 11, FTX fell apart and was revealed as a giant scam. Suddenly everyone hated effective altruists. Publications that had been feting us a few months before pivoted to saying they knew we were evil all along. I practiced rehearsing the words “I have never donated to charity, and if I did, I certainly wouldn’t care whether it was effective or not”. But during the flurry of intakes, screenings, and evaluations that UCSF gave me that month, the doctors asked “so what made you want to donate?” And I hadn’t rehearsed an answer to this one, so I blurted out “Have you heard of effective altruism?” I expected the worst. But the usual response was “Oh! Those people! Great, no further explanation needed.” When everyone else abandoned us, the organ banks still thought of us as those nice people who were always giving them free kidneys. We were giving them a lot of free kidneys. When I talked to my family and non-EA friends about wanting to donate, the usual reaction was “You want to what?!” and then trying to convince me this was unfair to my wife or my potential future children or whatever. When I talked to my EA friends, the reaction was at least “Cool!”. But pretty often it was “Oh yeah, I donated two years ago, want to see my scar?” Most people don’t do interesting things unless they’re in a community where those things have been normalized. I was blessed with a community where this was so normal that I could read a Vox article about it and not vomit it back out. This is surprising, because kidney donation is only medium effective, as far as altruisms go4. The average donation buys the recipient about 5 - 7 extra years of life (beyond the counterfactual of dialysis). It also improves quality of life from about 70% of the healthy average to about 90%. Non-directed kidney donations can also help the organ bank solve allocation problems around matching donors and recipients of different blood types. Most sources say that an average donated kidney creates a “chain” of about five other donations, but most of these other donations would have happened anyway; the value over counterfactual is about 0.5 to 1 extra transplant completed before the intended recipient dies from waiting too long. So in total, a donation produces about 10 - 20 extra quality-adjusted life years. This is great - my grandfather died of kidney disease, and 10 - 20 more years with him would have meant a lot. But it only costs about $5,000 - $10,000 to produce this many QALYs through bog-standard effective altruist interventions, like buying mosquito nets for malarial regions in Africa. In a Philosophy 101 Thought Experiment sense, if you’re going to miss a lot of work recovering from your surgery, you might as well skip the surgery, do the work, and donate the extra money to Against Malaria Foundation instead5. Obviously this kind of thing is why everyone hates effective altruists. People got so mad at some British EAs who used donor money to “buy a castle”. I read the Brits’ arguments: they’d been running lots of conferences with policy-makers, researchers, etc; those conferences have gone really well and produced some of the systemic change everyone keeps wanting. But conference venues kept ripping them off, having a nice venue of their own would be cheaper in the long run, and after looking at many options, the “castle” was the cheapest. Their math checked out, and I believe them when they say this was the most effective use for that money. For their work, they got a million sneering thinkpieces on how “EA just takes people’s money to buy castles, then sit in them wearing crowns and waving scepters and laughing at poor people”. I respect the British organizers’ willingness to sacrifice their reputation on the altar of doing what was actually good instead of just good-looking. I worry that people use suffering as a heuristic for goodness. Mother Teresa becomes a hero because living with lepers in the Calcutta slums sounds horrible - so anyone who does it must be really charitable (regardless of whether or not the lepers get helped). Owning a castle is the opposite of suffering - it sounds great - therefore it is fake charity (no matter how much good you do with the castle). This heuristic isn’t terrible. If you’re suffering for your charity, then it must seem important to you, and you’re obviously not doing it for personal gain. If you do charity in a way that benefits you (like gets you a castle), then the personal gain aspect starts looking suspicious. The problem is the people who elevate it from a suspicion to an automatic condemnation. It seems like such a natural thing to do. And it encourages people to be masochists, sacrificing themselves pointlessly in photogenic ways, instead of thinking about what will actually help others. But getting back to the point: kidney donation has an unusually high ratio of photogenic suffering to altruistic gains. So why do EAs keep doing it? I can’t speak for anyone else, but I’ll speak for myself. It starts with wanting, just once, do a good thing that will make people like you more instead of less. It would be morally fraught to do this with money, since any money you spent on improving your self-image would be denied to the people in malarial regions of Africa who need it the most. But it’s not like there’s anything else you can do with that spare kidney. Still, it’s not just about that. All of this calculating and funging takes a psychic toll. Your brain uses the same emotional heuristics as everyone else’s. No matter how contrarian you pretend to be, deep down it’s hard to make your emotions track what you know is right and not what the rest of the world is telling you. The last Guardian opinion columnist who must be defeated is the Guardian opinion columnist inside your own heart. You want to do just one good thing that you’ll feel unreservedly good about, and where you know somebody’s going to be directly happy at the end of it in a way that doesn’t depend on a giant rickety tower of assumptions. Dylan Matthews wrote: As I’m no doubt the first person to notice, being an adult is hard. You are consistently faced with choices — about your career, about your friendships, about your romantic life, about your family — that have deep moral consequences, and even when you try the best you can, you’re going to get a lot of those choices wrong. And you more often than not won’t know if you got them wrong or right. Maybe you should’ve picked another job, where you could do more good. Maybe you should’ve gone to grad school. Maybe you shouldn’t have moved to a new city. So I was selfishly, deeply gratified to have made at least one choice in my life that I know beyond a shadow of a doubt was the right one. …and it really resonated. Everything else I try to do, there’s a little voice inside of me which says “Maybe the haters are right, maybe you’re stupid, maybe you’re just doing the easy things. Maybe you’re no good after all, maybe you’ll never be able to figure any of this out. Maybe you should just give up.” The Talmud is very clear: that voice is called the evil inclination, and it dwells in the left kidney. There is only one way to shut it off forever. I was ready. V. You might not be a masochist. But hospitals are sadists. They want to hear you beg. After I submitted the donation form, I was evaluated by a horde of indistinguishable women. They all had titles like “Transplant Coordinator”, “Financial Coordinator”, and “Patient Care Representative”. Several were social workers; one was a psychiatrist. They would see me through a buggy version of Zoom that caused various parts of their body to suddenly turn into the UCSF logo, and they all had questions like “Are you sure you want to do this?” and “Are you going to regret this later?” and “Is anyone pressuring you to do this?” and “Are you sure you want to do this?” After clearing that gauntlet came the tests. Blood tests - I think I must have given between 20 and 50 vials of blood throughout the screening process. Urine tests - both the normal kind where you pee in a cup, and a more involved kind where you have to store all your urine for 24 hours in a big jug, then take it to the lab. “Urinate into a jug” ought to be the easiest thing in the world, but some of the labs have overly complicated jugs that I, with my mere MD, couldn’t always get right - hence my experience accidentally pouring urine on myself in an Uber. Then came the big guns. Echocardiogram. MRI. One of my urine tests was slightly off, so I also got a nuclear kidney scan, where they injected radioactive liquid in me and monitored how long it took to come out the other end (I remember asking a friend “Can I use your bathroom? My urine might be slightly radioactive today, but it shouldn’t be enough to matter.”) Finally, five months after I originally applied, I got a phone call from the Transplant Coordinator. The test results were in, and . . . I had been rejected because I’d had mild childhood OCD. This was something I’d mentioned offhandedly during one of the psych evaluations. As a child, I used to touch objects in odd patterns that only made sense to me. I got diagnosed with OCD, put on SSRIs for a while, finally did therapy at age 15, hadn’t had any problems since. I still go back on SSRIs sometimes when I’m really stressed, and will grudgingly admit to the occasional odd-pattern-touching when no one’s looking. But it’s nothing anyone would know about if I didn’t tell them! It was mild even at age 15, and it’s been close-to-nonexistent for the past twenty years! Now I’m a successful psychiatrist who owns his own psychiatry practice and helps other people with the condition! I told them all this. They didn’t care. I asked them if there was anything I could do. They said maybe I could go to therapy for six months, then apply again. I asked them what kind of therapy was indicated for mild OCD that’s been in remission for twenty years. They sounded kind of surprised to learn there were different types of therapy and said whatever, just talk to someone or something. I asked them how frequent they thought the therapy needed to be. They sounded kind of surprised to learn that therapy could have different frequencies, and said, you know, therapy, the thing where you talk to someone. I asked them if they actually knew anything about OCD, psychotherapy, or mental health in general, or if they had just vaguely heard rumors that some people were bad and crazy and shouldn’t be allowed to make their own decisions, and that a ritual called “therapy” could absolve one of this impurity. They responded as politely as possible under the circumstances, but didn’t change their mind. I wasn’t going to waste an hour a week for six months, and spend thousands of dollars of my own extremely-not-reimbursed-by-UCSF money, to see a randomly-selected therapist for a condition I’d gotten over twenty years ago, just so I could apply again and get rejected a second time. This was one of the most infuriating and humiliating things that’s ever happened to me. We throw around a lot of terms like “stigma” and “paternalism”, and I’ve worked with patients who have dealt with all these issues (it’s UCSF in particular a surprising amount of the time!). But I was still surprised how much it hurt when it happened to me. Being denied the right to control your own body because of some meaningless diagnosis on a chart somewhere is surprisingly frustrating, even compared to things that should objectively be worse. I thought I was going to be able to do a good deed that I’d been fantasizing about for years, and some jerk administrator torpedoed my dreams because I had once, long ago, had mild mental health issues. So I gave up. I spent the next few weeks unleashing torrents of anti-UCSF abuse at anyone who would listen. This turned out to be very productive! When I was unleashing a torrent of anti-UCSF abuse to Josh Morrison of WaitlistZero, he asked if I’d tried other hospitals. I hadn’t. I’d assumed they were all in cahoots. But Josh said no, each hospital had their own evaluation process. Weill Cornell, a hospital in NYC, was one of the best transplant centers in the country, and had a reputation for fair and thoughtful pre-donor screening. Why didn’t I talk to them? NYC was far away, and I hate to travel, but I was just angry enough to accept. At this point I’d forgotten whatever good altruistic motivations I might have originally had and was fueled entirely by spite. Getting my kidney taken out somewhere else felt like it would be a sort of victory over UCSF. So I went for it. Cornell was lovely. They tried to do as much of the process as they could via Californian intermediaries, so that I only had to fly to New York twice. Their psychiatrist evaluated me, listened to me explain my weak history of OCD, then treated me like a reasonable adult who tells the truth and can handle his own medical decisions. They were concerned that I sometimes self-prescribed Lexapro to deal with anxiety. But we agreed on a compromise: I found another psychiatrist, let her give me the exact same prescription of Lexapro at a much higher cost to my insurance, and that resolved the problem. So in late September 2023 - ten months after I started the process - I finally got fully cleared to donate, surgery set for October 12. VI. I knew, in theory, that anaesthetics existed. Still, it’s weird. One moment you’re lying on a table in the OR, steeling yourself up for one of the big ordeals of your life. The next, you’re in a bed in the recovery room, feeling fine. The operation - this thing you’ve been thinking about and dreading for months - exists only as a lacuna in your memory. Not even some kind of fancy lacuna, where you remember the darkness closing in on you beforehand, or have to claw yourself back into consciousness afterwards. The most ordinary of lacunas, like a good night sleep. There was no pain, not at first. The painkillers and nerve blocks lasted about a day after the surgery. By the time they wore off, it was more of a dull ache. The hospital offered me Tylenol, and I wanted to protest - really? Tylenol? After major surgery? But the Tylenol worked. Some people will have small complications (I am a doctor, pretty jaded, and my definition of “small” may be different from yours). Dylan Matthews wrote about an issue where his scrotum briefly inflated like a balloon (probably this is one of the ones that doesn’t feel small when it’s happening to you). I missed out on that particular pleasure, but got others in exchange. I had an unusually hard time with the catheter - the nurse taking it out frowned and said the team that put it in had “gone too deep”, as if my urinary tract was the f@#king Mines of Moria - but that was fifteen seconds of intense pain. Then a week afterwards, just when I thought I’d recovered fully, I got bowled over by a UTI which knocked me out for a few days. But overall, I was surprised by the speed and ease of my recovery. A few hours after the surgery, I walked a few steps. After a day, I got the catheter out and could urinate normally again. After two days, I was eating “SmartGel”, a food substitute that has mysteriously failed to catch on outside of the immobilized-hospital-patient market. After three, I was out of the hospital. After four, I started easing myself back into (remote) work. After a week, I flew cross-country. . . . and then I got the UTI. If this section sounds schizophrenic, it’s because it’s a compromise between an original draft where I said nothing went wrong and it was amazing, and a later draft written after a haze of bladder pain. Just don’t develop complications, that’s my advice. Still, I recently heard from the surgeon that my recipient’s side of the surgery was a success, that my kidney was in them and going fine - and that put things back into perspective. To a first approximation, compared to the inherent gravity of taking an organ out of one person and putting it in a second person and saving their life - it was all easy and everything went well. When I look back on this in a decade, I’ll remember it as everything being easy and going well. Even now, with some lingering bladder pain, modern medicine still feels like a miracle. VII. In polls, 25 - 50% of Americans say they would donate a kidney to a stranger in need. This sentence fascinates me because of the hanging “would”. Would, if what? A natural reading is “would if someone needs it”. But there are 100,000 strangers on the waiting list for kidney transplants. Between 5,000 and 40,000 people die each year for lack of sufficient kidneys to transplant. Someone definitely needs it. Yet only about 200 people (0.0001%) donate kidneys to strangers per year. Why the gap between 25-50% and 0.0001%? Some of you will suspect respondents are lying to look good. But these are anonymous surveys. Lying to themselves to feel good, then? Maybe. But I think about myself at age 20, a young philosophy major studying utilitarianism. If someone had asked me a hypothetical about whether I would donate a kidney to a stranger in need, I probably would have said yes. Then I would have continued going about my business, never thinking of it as a thing real-life people could do. Part of this would have been logistics. I wouldn’t have known where to start. Do you need to have special contacts in the surgery industry? Seek out a would-be recipient on your own? Where would you find them? But more of it would have been psychological: it just wasn’t something that the people I knew did, and it would be weird and alienating for me to be the only one. This is going to be the preachy “and you should donate too!” section you were dreading all along, but I’m not going to make a lot of positive arguments. If 90% of the people who answer yes on those surveys are lying to feel good, then only 3 - 5% really want to donate. But bringing the donation rate from 0.0001% of people to 3 - 5% of people would solve the kidney shortage many times over. The point isn’t to drag anti-donation-extremists kicking and screaming to the operating table. The point is to reach the people who already want to do it, and make them feel comfortable starting the process. 20-year-old me was in that category. The process of making him feel comfortable involved fifteen years of meeting people who already done it. During residency, I met a fellow student doctor who had donated. Later, I got involved in effective altruism, and learned that movement leader Alexander Berger - a guy who can easily direct millions of dollars at whatever cause he wants - had donated his personal kidney as well. Some online friends. Some people I met at conferences. And Dylan Matthews, who I kept crossing paths with (most recently at the Manifest journalism panel). After enough of these people, it no longer felt like something that nobody does, and then I felt like I had psychological permission to do it. (obviously saints can do good things without needing psychological permission first, but not everyone has to be in that category, and I found it easier to get the psychological permission than to self-modify into a saint6.) So I’m mostly not going to argue besides saying: this is a thing I did, it’s a thing hundreds of other people do each year, getting started is as simple as filling out a form, and if it works for you, you should go for it7. When I woke up in the recovery room after surgery, I felt great. Amazing. Content, peaceful, proud of myself. Mostly this was because I was on enough opioids to supply a San Francisco homeless encampment for a month. But probably some of it was also the warm glow of having made a difference or something. That could be you! VIII. The ten of you who will listen to this and donate are great. That brings the kidney shortage down from 40,000 to 39,990/year. Everyone knows we need a systemic solution, and everyone knows what that solution will eventually have to be: financial compensation for kidney donors. But so far they haven’t been able to get together enough of a coalition to overcome the usual cabal of evil bioethicists who thwart every medical advance. My kidney donation “mentor”8 Ned Brooks is starting a new push - the Coalition To Modify NOTA - which proposes a $100,000 refundable tax credit - $10,000 per year for 10 years - for kidney donors. There would be a waiting period and you’d have to get evaluated first, so junkies couldn’t walk in off the street and get $100K to spend on fentanyl. No intermediate company would “profit” off the transaction, and rich people wouldn’t be able to pay directly to jump in line. It would be the same kidney donation system we have now, except the donors get $100,000 back after saving the government $1MM+. (the libertarian in me would normally prefer a free market, but “avoid taxes by selling your organs” also has a certain libertarian appeal) This came up often when I talked to other donors. They all had various motivations, but one of the things they cared about was being able to advocate for these kinds of systemic changes more effectively. I personally have been wanting to push this in an essay here for a while, but it seemed hypocritical to play up the desperate kidney shortage while I still had two kidneys. Now I can support NOTA modification whole-heartedly . . . full-throatedly? . . . it’s weird how many of these adverbs involve claims to still have all of your organs. This is also one of the answers to the question I asked in section IV: how do you balance acts of heroic altruism that everyone will love you for vs. acts of boring autistic altruism that will make everyone hate you, but which will accomplish more good in the end?) Coalition To Modify NOTA is full of previous living kidney donors, who are using the moral clout and recognition they’ve gotten to get attention and change the system in an unglamorous way. I find this an admirable way of squaring the circle: do the flashy heroic things to gain social capital, then spend the social capital on whatever’s ultimately most important. If you get one takeaway from this, let it be that those guys who bought the castle were good guys. Two takeaways, and it’s that plus modify NOTA. Three takeaways, and you should feel permission to (if you want) donate a kidney. You can sign up here.9 Feel free to email me at scott@slatestarcodex.com if you have questions about the process. 1Further perspective: I’m 38, which gives me a 2/million total chance of dying per day. So the likelihood that I would die during my kidney operation equals the likelihood that I would die during a randomly chosen two months of everyday life. 2Maybe, kind of. Our knowledge of how radiation causes cancer comes primarily from Hiroshima and Nagasaki; we can follow survivors who were one mile, two miles, etc, from the center of the blast, calculate how much radiation exposure they sustained, and see how much cancer they got years later. But by the time we’re dealing with CAT scan levels of radiation, cancer levels are so close to background that it’s hard to adjust for possible confounders. So the first scientists to study the problem just drew a line through their high-radiation data points and extended it to the low radiation levels - ie if 1 Sievert caused one thousand extra cancers, probably 1 milli-Sievert would cause one extra cancer. This is called the Linear Dose No Threshold (LDNT) model, and has become a subject of intense and acrimonious debate. Some people think that at some very small dose, radiation stops being bad for you at all. Other people think maybe at low enough doses radiation is good for you - see this claim that the atomic bomb “elongated lifespan” in survivors far enough away from the blast. If this were true, CTs probably wouldn’t increase cancer risk at all. I didn’t consider myself knowledgeable enough to take a firm position, and I noticed eminent scientists on both sides, so I am using the more cautious estimate here. 3I told them I had an aunt who died of radiation-induced cancer. It’s true, but I feel grubby for bringing her into this; I thought doctors would be more likely to listen to an emotional story than cold logic. 4EAs have been debating the exact effectiveness of kidney donations for a long time. You can find good skeptical arguments by Jeff Kaufman and Derek Shiller, and good arguments in favor by Alexander Berger and Tom Ash. 5Outside of Philosophy 101 thought experiments, there’s a nonprofit that will often reimburse you for lost wages from your donation. 6Self-modifying into a person who can act boldly without social permission is a more general solution and has many other advantages. But the long version involves living a full life of accumulating moral wisdom, and the short version starts with removing guardrails that are there for good reasons. 7But here are some practical points you might not already appreciate: You shouldn’t have to pay much money. If, like me, you need to travel (eg to New York), kidney related charities will reimburse your travel costs (in theory, I haven’t yet proven this, and a few costs were illegible and I decided not to submit them).
Lumina

Lumina is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between December 07, 2023 and May 29, 2024. The archive places it in contexts such as "BCS3-L1 (brand name “Lumina”) is a genetically-modified strain of the tooth decay bacterium streptococcus mutans"; "using Lumina makes things worse"; "Lumina might activate Antabuse". It most often appears alongside Aaron, FDA, BCS3-L1.

Article page
Lumina
Mention count
4
Issue count
4
First seen
December 07, 2023
Last seen
May 29, 2024
December 07, 2023 · Original source
Lantern Bioworks says they have a cure for tooth decay. Their product is a genetically modified bacterium which infects your mouth, outcompetes all the tooth-decay-causing bacteria, and doesn’t cause tooth decay itself. If it works, it could make cavities a thing of the past (you should still brush for backup and cosmetic reasons).
BCS3-L1 (brand name “Lumina”) is a genetically-modified strain of the tooth decay bacterium streptococcus mutans.
It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria. The antibiotic helps it win the Darwinian competition in your mouth to become King Of The Oral Bacteria. The alcohol metabolism means it won’t produce lactic acid (and so won’t cause tooth decay). The peptide knockout prevents it from transferring genes back and forth with other bacteria that might either inactivate it or leak its advantage. 1.1: Where did this come from? Who invented it? Professor Jeffrey Hillman of the University of Florida. In 1985, he was surveying the microorganisms on his graduate students’ teeth (as you do). One grad student had an unusual strain of S. mutans with a natural version of mutations 1 and 2 (it produced mutacin-1140, and was resistant to it). Hillman realized the potential, and spent the next few decades adding mutations 3 and 4 and testing the results. 1.2: So how did it end up with a tiny startup in 2023? Professor Hillman started a company “Oragenics” and applied for FDA approval. The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects (including an intranasal COVID vaccine!) Aaron heard this story and figured that brash, move-fast-and-break-things Silicon Valley biotech might be able to find an alternative route to commercialization. The strain was off-patent, so he first tried to synthesize it himself from the clues in Hillman’s published papers. When that didn’t work, he made a deal with Oragenics for 10% of profits in exchange for samples and the full recipe. 2: How do you use it? To apply, you brush your teeth with a special pumice-based product that removes your existing tooth bacteria, then swab it on with a q-tip. One dose is sufficient; once you use it, it’s in your mouth approximately forever. 2.1: As users kiss their loved ones, who kiss others in turn, will this spread exponentially and take over the world? There was originally some concern about this, but no. Remember, the original bacterium was found in the wild, in a random grad student’s mouth forty years ago. There must be thousands of people walking around with various naturally-occurring BCS3-L1-like things. So probably this isn’t a risk for some kind of weird pandemic. Existing mouth bacteria have fortified their position and have a strong home field advantage. This is why you need to brush your teeth with the special product to apply Lumina. Lantern’s safety documents note that couples who kiss constantly do end up with similar oral microbiomes. So maybe enough kissing - especially kissing just after a dental cleaning when your existing bacteria are at their weakest - could spread the strain accidentally, very slowly. This rate of spread would be comparable to the rate of spread of every other mouth bacterium. 2.2: When a user kisses their newborn baby, will it spread to the baby? Okay, this one is true. Babies have no existing mouth bacteria, and get theirs from their parents’ kisses. Not necessarily their first kiss as a newborn (newborns have no teeth, and BCS3-L1 needs teeth to live), but their first kiss after teeth grow in. If you get this, you’re probably getting it for your whole future family line. 2.3: If you wanted to get rid of it, could you? Some kind of extreme course of oral antibiotics that nukes everything growing in your mouth would probably eradicate BCS3-L1, but this hasn’t been tested and would have side effects. 3: Is it dangerous to have bacteria secreting an antibiotic in your mouth? Does this mean you’re on a weak antibiotic all the time? There are already bacteria secreting antibiotics in your mouth. Microbes are in constant war with other microbes, and antibiotics are one of their favorite weapons - remember, penicillin comes from a fungus. Because bacteria secrete just enough antibiotic to clear their local area, these are tiny quantities, much less than you’d get from taking a medical-grade antibiotic pill. Lantern says the levels of mutacin-1140 dilute to irrelevance “tens of microns” away from the secreting bacteria. In any case, it’s a weak antibiotic that doesn’t survive the digestive tract (Hillman originally hoped to market the antibiotic too, but found it didn’t get absorbed and broke down too quickly). Neither the grad student with the original strain nor any of Hillman’s test subjects had any noticeable health issues. See also Lantern’s Safety Review FAQ. 3.1: Is it bad to disrupt your normal mouth microbiome? When talking about BCS3-L1 “taking over” the mouth, this just means it takes over the streptococcus mutans niche. There are still other bacteria and fungi in the mouth. The mutacin antibiotic might still disrupt these other bacteria (probably not fungi). But strains like BCS3-L1 already exist in the wild (eg the original grad student), and lots of bacteria and fungi secrete antibiotics, so it doesn’t seem like having mutacin-secreting organisms in your mouth makes you some extreme oral microbiome outlier. If you eat a normal Western diet, your mouth microbiome is already pretty far from the design specs, and it’s unclear if using Lumina makes things worse. 3.2: Will the other bacteria develop resistance to the antibiotic? Mutation 4 prevents BCS3-L1 from “leaking” its own resistance. Although in theory other bacteria could develop resistance, mutacin-1140 is a hard antibiotic to develop resistance to, and the other bacteria would have to do it in the short period before BCS3-L1 kills them off and establishes its own home field advantage. In practice, Professor Hillman found that BCS3-L1 remained dominant over many years and nothing developed resistance to it. Even if a mutacin-resistant strain does develop in one person’s mouth, it will have a hard time getting to anyone else’s mouth, so widespread immunity is unlikely. 4: Is it dangerous to have bacteria secreting alcohol in your mouth? Will you get drunk? Most people already have some alcohol-secreting bacteria in their bodies. (there’s a condition called auto-brewery syndrome where those bacteria get out of control and produce enough alcohol to make someone drunk. It’s vanishingly rare in real life, but more common in the legal system: “You gotta believe me, Officer, it was just auto-brewery syndrome!”) The average person has enough of these bacteria in their gut to have a natural blood alcohol level - even after zero drinks - of about 0.1 mg/dl. Under pessimistic assumptions, BCS3-L1 will add another 0.2 mg/dl, bringing the total to 0.3. This is still a pretty normal number that some people have naturally (it would bring the average customer from the ~50th to the ~80th percentile of natural blood alcohol). It’s also far from the usual threshold for feeling tipsy (30 mg/dl) or too drunk to drive (80 mg/dl). Under more realistic assumptions, the amount of alcohol produced by BCS3-L1 probably isn’t significant even by the very low standards of natural blood alcohol concentrations. 4.1: Are there some unusual scenarios where this amount of alcohol might matter? I don’t think Lantern has studied Breathalyzers. Since the alcohol is directly in your mouth, it might have disproportionate effect on a Breathalyzer compared to alcohol in your blood. I think it’s probably still too low to matter, but this is a wild guess. There is conjecture that “non-alcoholic steatohepatitis”, a liver disease in which non-alcoholics get the same kind of liver damage that alcoholics usually get, might be associated with endogenous blood alcohol in the high normal range. If I’m understanding this paper right, it’s probably because the gut produces levels of alcohol consistent with auto-brewery syndrome, the liver goes into overdrive and metabolizes it away (prevents auto-brewery syndrome from developing), but the liver is damaged in the process the same as if it had to go into overdrive to metabolize normal binge drinking. Since BCS3-L1 produces much less alcohol than auto-brewery, I think it wouldn’t cause non-alcoholic steatohepatitis, even though it might produce final blood alcohol levels similar to those associated with the condition. I was originally worried that Lumina might activate Antabuse, an anti-alcoholism drug that prevents drinking by causing a very unpleasant (sometimes dangerous) reaction to ethanol. There are some past cases of Antabuse being activated by really trivial quantities, like the alcohol in a chicken marsala dish or a mouth wash. But no, I think BCS3-L1 is less than this too. Chicken marsala can contain several grams of alcohol per serving, but BCS3-L1 probably only produces a few milligrams per day. If you swallow 1/10 of your mouthwash, that’s about 200 mg of alcohol - again, BCS3-L1 is probably only a few milligrams a day. Antabuse usually activates around a BAC of 5 mg/dl; BCS3-L1 only gives you a BAC of about 0.3 mg/dl. Again, this really is a tiny amount of alcohol. There might be other edge cases like these. Lantern offers a $100 bounty to anyone who can come up with one they haven’t thought of yet (and sometimes extra if you’re willing to help them research them). 4.2: Has anyone tested this in real life? As mentioned before, the mutacin-releasing strain (with mutations 1 and 2) exists in the wild and was extensively tested by Professor Hillman. The full strain with all four mutations has undergone some testing by Dr. Hillman, but nobody had officially infected themselves with it until two months ago, when Aaron finally synthesized it and tried it on himself. He says he’s usually “a lightweight” as far as alcohol goes, and hasn’t felt any different over the past two months. When first infected, BCS3-L1 makes up almost 100% of the microbiome (because you deliberately removed all your other bacteria, then infected yourself with it). Over time, other bacteria creep back in; over an even longer period (years?), BCS3-L1 reclaims lost territory and reaches a steady state. But the point is that Aaron probably has already passed his period of highest BCS3-L1 activity, and felt nothing. My wife infected herself about a month ago, and I haven’t noticed her having worse judgment or becoming more impulsive. But at baseline she was the sort of person who would infect herself with an untested genetically-modified bacteria strain, so there might be floor effects. 5: What’s the plan to sell Lumina? The plan is: Phase 1: (January 2024) Sell to biohackers in Prospera for $20,000.
December 11, 2023 · Original source
4: Since I was pretty gung ho about the Lumina tooth probiotic, I want to link the good criticism I found as a counterbalance (without necessarily endorsing it). Here’s someone from Hacker News doubting that it will colonize the mouth (or do much if it does) - though see comments below. Here’s an endodontist talking about how hard it is to study this or get any evidence that it works. Some other people pointed out that the graph on the post shows only 50% colonization after one year; Aaron says he has other information showing it eventually reaches near 100% colonization and he’ll get that to me soon. Some people were extremely skeptical about whether any of this was even real, so here’s an NYT article about the original Hillman research from 2004 that will hopefully put those doubts to rest. I agree that there isn’t proof of efficacy and it will be hard to prove that, but I think the suggestive evidence compares well to other supplements I respect (albeit not $20K supplements), and no one in the comments had a good story for why it would cause harm - so I chose to take the free sample. I’ll let you know if anything terrible happens to me! Till then, you can also check the prediction markets.
April 16, 2024 · Original source
Lumina, the genetically modified anti-tooth-decay bacterium that I wrote about in December, is back in the news after lowering its price from $20,000 to $250 and getting endorsements from Yishan Wong, Cremieux, and Richard Hanania (as well as anti-endorsements from Saloni and Stuart Ritchie). A few points that have come up:
The rats with the new strain (BCS3-L1) got only 1/3 the normal rats’ “caries score”. But they didn’t get a score of zero. So maybe claims like “BCS3 represents a complete cure for cavities” are overblown. Why didn’t rats with the new strain get zero dental caries? Bacteria other than S. mutans can also cause cavities, so maybe it’s one of those. Rat trials are famous for results that don’t replicate in human trials, so take these with a grain of salt. 3: What did the latest colonization studies show? Aaron was able to retest six people who got free samples in December. Four of those people still have the bacterium. The other two don’t. Of the two failures, one had an active cavity at the time the strain was applied (which interferes with the oral microbiome), and the other had his wisdom teeth removed (which involves rinsing the mouth with strong antiseptics). Aaron hopes this shows the strain will stick around in most normal situations (though the failure in the presence of active cavities is disappointing). 4: Any new concerns about side effects? In my original post, I mentioned the possibility that this would set off Breathalyzers. Lantern was able to test this, and proved that it wasn’t a problem. Yesterday, Lao Mein suggested on Less Wrong that it might raise oral cancer risk - their post focused on people with ALDH deficiency (most common in Asians) but the calculations are too vague to be sure exactly which groups should and shouldn’t worry. This is less than 24 hours old, the company hasn’t replied yet, and is still developing. I’ll try to update people if anyone gets more clarity on this. Someone on the post mentioned that they’ve gotten worse hangovers since using the product, maybe because the constant trickle of alcohol changed the way gut flora metabolize it. 5: Any other meaningful results since the samples? Cremieux says his breath smells better. Some people have objected to this claim on the grounds that it takes ~12 months before the bacterium has colonized your mouth. One of the figures in my earlier post suggested that the bacterium might start strong, retreat for a while, and then take 12 months to fully colonize, so that might potentially explain his findings. But also, is it biologically plausible that this prevents bad breath? My impression was that bad breath came from other bacterial byproducts besides lactic acid. It might be possible in theory that the same metabolic changes that switch lactic acid to alcohol disrupt these other byproducts, but it seems kind of unlikely. An alternate explanation is that, in order to apply this product at all, you need to do a dentist-style teeth cleaning that kills your previous mouth bacteria. Maybe that improves the bad breath regardless of whether you add the Lumina afterwards? Some other people have said their mouth feels fresher or something, but realistically all of this is overwhelmingly likely to be placebo. 6: Do I “endorse” Lumina? Richard Hanania has a post about how he trusts Lumina because I’ve endorsed them. It’s extremely kind and I appreciate his respect. But also, the most I said in the original post was that I was still debating whether or not to get the treatment. My real opinion, as precisely as I can express it, is: Advance of approximately the same magnitude as fluoride: 5%
If you’re a poor person, spending your last $250 on this because you desperately want to cure your cavity problem, and you would be devastated if it didn’t work or if had any side effects - then you shouldn’t buy Lumina.
May 29, 2024 · Original source
17: Only reporting this one out of duty: pharma researcher/blogger Trevor Klee posted a list of concerns about Lumina’s anti-cavity probiotic. Many of them seemed to misunderstand the science involved, and a few were outright false. I was particularly annoyed about the claim that I had gotten a free sample “in exchange for good publicity” - I specified on my public, easy-to-find blog post that I got it because my wife consulted for the company.
Aaron, CEO of Lumina, responded with an email asking him to take it down; it technically did not threaten him with a defamation suit, but had strong vibes to that effect. Then another Lumina employee independently sent an email actually threatening to sue for defamation. Trevor very reasonably published both emails on his blog, people very reasonably turned against Lumina, and I understand Lumina will have a statement or something soon.
I think Trevor should have been more careful with his original accusations, but I also think defamation lawsuit threats are toxic and chill the flow of information, that this community has strong norms against them except in extreme cases, and that Lumina violated those norms. ESH but I hold Lumina to a higher bar and especially hope they do better in the future.
Marvel

Marvel is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between April 27, 2023 and January 16, 2026. The archive places it in contexts such as "competence at execution (both of which the Marvel movies have)"; "Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films"; "no Marvel movies". It most often appears alongside Trump, Biden, California.

Article page
Marvel
Mention count
4
Issue count
4
First seen
April 27, 2023
Last seen
January 16, 2026
April 27, 2023 · Original source
» Is it just that Marvel feels optimized to make you like it and buy action figures, and liking it and buying action figures would make me feel like a little puppet being jerked back and forth by the Disney Corporation?
Admit that it would be indistinguishable from other myths, but say that the “quality” of the Mabinogion comes from something outside the text, like the fact that it’s old, or that it inspired a nation, or that it takes effort to engage with. My lack of a good answer to this experiment makes me reluctant to make too much hinge on abstracted “quality”, separate from “ability to make many people very much enjoy the thing” or “competence at execution” (both of which the Marvel movies have). The Ern Malley hoax, where lots of people who supposedly had good taste were tricked into declaring something high-quality when it superficially appeared to have the characteristics of high-quality things (mildly incomprehensible, used big words, written by someone who toiled in obscurity and died tragically) makes me even more doubtful. My cynical null hypothesis is that we call competently-executed things tasteful/high-quality if they require a lot of erudition to understand and make good class markers, and throw them in the trash with the MCU if they’re easy to appreciate and make terrible class markers. But emotionally I’m not ready to accept this. Emotionally, everyone who likes things more prestigious than what I like is a snob who’s faking it, and everyone who likes things less prestigious than what I like is a boor who doesn’t understand true art. This probably isn’t literally correct but I don’t know which of those two beliefs to abandon. Back to Sam: maybe a better way of summarising my position is that nerds like things in a way that’s orthogonal to quality. let’s take an example of something that’s both very popular and widely agreed to be good – say, the poetry and plays of shakespeare. if you wanted to identify yourself as someone who liked shakespeare, there are actually two ways of doing this. you could deeply immerse yourself in the study of shakespeare, and even become a shakespearean actor or a professor of tudor and jacobean theatre. or you could change your twitter avi to a picture of shakespeare, take plenty of selfies while reading hamlet, wear the t-shirt, and get in endless feuds with people who prefer marlowe or jonson. in fact, you could go down the latter route without ever actually reading any of his plays. (there are a few people who do precisely this.) these are two different ways of intensively liking something. and i think it makes sense to say that while the first example does not make you a nerd, the second one sort of does. Okay, this one feels more like cheating. I’m imagining a two-by-two square: …where Sam fills in the northwest and southeast squares, then claims a correlation, draws a line, and points to high-status/deep-engagement as a single unified concept. But the southwest square could be “writes a wacky Shakespeare fanfiction, Romeo & Juliet II, in blank verse and period-appropriate language”, and the northeast square could be “publishes a dissertation on some irrelevant aspect of word frequency changes across English plays to prove something about linguistics”. And then having conflated these two things, he goes on to conflate a third thing, Shakespeare vs. Marvel. I’m not up to date on what goes on in academic literature departments, but Freddie de Boer says they’re increasingly offering “Spiderman Studies” classes in attempts to stay culturally relevant; probably Spiderman professors engage with Spiderman on the same deep level that Shakespeare professors engage with Shakespeare. If we made this a cube - high-status vs. low-status forms of engagement along one axis, Shakespeare vs. Spiderman along another axis, and deep vs. shallow engagement along the third - would anything be left of the “nerd” cluster as Sam describes it? I’m not sure. 2. Comments With Strong Opinions On The Definition Of Nerds, Geeks, Etc There were many of these. One common theme was that in the 70s, “nerd” was almost synonymous with “person who is only into unpopular things”, for example sci-fi, comics, and RPGs, all of which were unpopular in the 70s. Then those things became very popular, but the people who were interested in them still get called “nerds”. So now people like Kriss use “nerd” almost synonymously with “person who is only into popular things”. So we have a word which denotes either interest in unpopular things or interest in popular things, depending on who’s using it and when they last updated their lexicon. In the 70s, it was more reasonable to group “interested in math and computers” and “interested in sci-fi and RPGs” together, because both were unpopular and tended to involve the same group of socially maladept young men. Now math is still hard and unpopular; computers are hard in the sense that it’s tough to learn programming languages, but universally used and beloved; sci-fi and RPGs are very popular, and the typical sci-fi fan is closer to a socially-adept albeit “quirky” young woman. If words are hidden inferences, the inference represented by “nerd” - that sci-fi fandom, interest in math, interest in computers, maleness, poor social skills, and nonconformity with mainstream interests all go together - is now thoroughly false, dooming us to conversations like this one. Attempts to repurpose the several different words used to refer to the math/sci-fi/awkward/unpopular cluster to represent different aspects of its successor clusters have mostly failed. Sample comments from this section: Coagulopath writes: To me, being a nerd requires a degree of swimming against the cultural tide. It's weird and unpopular to be into trains, so the fact that you are indicates you have a bit of character (or are socially oblivious, which is also kind of endearing). The problem (and I think Kriss alludes to this) is that nerd stuff went mainstream in the past few decades. Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films. There's no longer any sense that nerds are the underdog. But what does it say about you when you wear a Star Wars shirt? You're pledging allegiance to the biggest, most popular club imaginable. Is that a brave stance? Those people always make me think "if you lived in the SW universe, you'd be on the side of the Empire". In general, I am creeped out by effusive public adoration for things that are near-universally loved. Like The Beatles. Or bacon. Or dogs. Or science (Neil DeGrasse Tyson's whole shtick). Regardless of how I feel about those things on the object level, there's no glory in joining a culture war when you're signing on to the winning side. Tolaughoftenandmuch writes: All this is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, Ghatanathoah writes: I also wouldn't say that nerd stuff only went mainstream in the last decade, it's not like the first 3 Star Wars movies were obscure arthouse pictures. I think the reason Marvel took off is just innovations in storytelling: movie producers finally figured out a way to adapt the gloriously arcane and convoluted lore of superhero comics in a way that could appeal to mainstream audiences in addition to nerds (much how George Lucas figured out how to get mainstream audiences to love the space operas nerds had been enjoying for decades before 1977). And Melvin writes: Comic book movies had always been pretty popular. Superman was the top grossing movie of 1979 despite coming out in 1978. Superman 2 was the second top grossing movie of 1981. Batman was the second top grossing movie of 1989. Batman Returns was the top grossing movie of 1992. Batman Forever was the top grossing movie of 1995. Spider-man was the third top grossing movie of 2002 (behind Lord of the Rings and Harry Potter movies). That's about all I can be bothered looking up right now but you get the idea, superhero movies have been popular since the 1970s. Kaitian writes: I think being a nerd requires being a bit socially clumsy about your interest, and talking or signalling about it in situations where most people don't expect it. So being a nerd about completely mainstream stuff like pop music or football is not possible, that's just fandom. Being a nerd about very well known and relatively well-respected stuff like classical music or birdwatching is rare, because most people who are classy enough to care about the thing in the first place are also classy enough to know when to shut up about it. But comics? Star trek? Power metal? They have fairly low barriers to entry *and* most people don't care about them, so there's plenty of opportunities to bring it up to people who don't want to hear about it. So that's why I think nerdery usually attaches itself to the typical targets. J.R. Leonard has as good a terminology proposal as anyone: I think what's missing is that Kriss uses "nerds" as his foil, but what he's talking about would better be described as fan culture. Deiseach teaches us the etymology of “geek”. The very distant etymology is from German gek, a relative of “cackle” → geck, a fool/madman (who was presumably cackling all the time). But this comes down to us through the early American institution of the geek show. From Wikipedia (cw: disturbing): Geek shows were an act in traveling carnivals and circuses of early America and were often part of a larger sideshow. The billed performer's act consisted of a single geek, who stood in the center ring to chase live chickens. It ended with the performer biting the chickens' heads off and swallowing them. The geek shows were often used as openers for what are commonly known as freak shows. It was a matter of pride among circus and carnival professionals not to have traveled with a troupe that included geeks. Geeks were often alcoholics or drug addicts, and paid with liquor – especially during Prohibition – or with narcotics. More obvious but I went surprisingly long without realizing it: “fan” (as in “sports fan”) is just short for fanatic. 3. Comments About Collecting The veteran collectors in the comments said that my theory (the Internet makes collecting too easy) was only a small part of the decline. The bigger part is that most coin collecting begins with the wonder of finding a rare coin in your change, and most stamp collecting begins with the wonder of finding a rare stamp on your mail, and the rise of credit cards and emails means people aren’t handling coins and stamps as much in their daily lives. Tom Metcalf writes: I'd guess many coin collectors got their start being patient enough to sort through change to see if they had e.g. a wheat cent or silver dime, but first of all, who pays with cash and gets change, and the chances of finding something collectible are orders of magnitude smaller than, say, the '90s. And stamp collectors would have started saving the stamps on mail sent to their house, but how frequently do you get stamped mail anymore? My 79-year old father goes to stamp shows, because one of his hobbies is to buy sheets of old but common unused stamps for less than face value. They are still valid postage, and then he uses them to personalize the stamps he puts on letters he sends to various people. And most of the other people at stamp shows are about his age. He does have some stamps he thinks are interesting that he's held onto, but the dealers at the stamp shows think they're common and uninteresting. So there's a decreasing number of stamps that might be "worth something" and a net loss of collectors in the hobby, and then every time a collector dies and his heirs have no interest in his collection and that many more stamps make their way to dealers who now have one less buyer. Too bad "sending paper letters with vintage but still valid stamps" never caught on with the hipsters. Art writes: The widespread adoption of email created a world where a letter is almost certainly junk mail or a bill. Nobody looks forward to hearing from a good friend from across the country now when picking up the day’s mail. If letters are not interesting why would stamps? The same for coins. Nobody uses cash, and getting a pile of coins with no significant value (inflation) is just an annoyance. These objects have passed into irrelevance. Still, it seems like some little pieces of joy and wonder have passed from our lives. Nathan Savir writes: I collect coins and I think the description of the hobby (and its putative death) isn't quite right. 1. Rare coins are in fact hard to find, even in today's internet world. They are usually sold in auctions, which might happen online, but still not that frequently. It's not unusual for examples some specific rare coin to be sold only once every few years. If the coin is also obscure, it may not be prohibitively expensive, so this kind of situation isn't the sole province of rich people. 2. One area of collecting is to get all the rare items. Another is to get all the minor varieties of a common item. These varieties may not be very rare, but it still takes a lot of effort to be able to distinguish them and to find them. Some collectors will obtain large numbers of relatively common coins and sort through and scrutinize them to try to identify interesting varieties. 3. An important part of collecting is getting good deals. This is surely a lot harder than it used to be because sellers can more easily figure out what things are worth and you won't find something grossly underpriced in a random antique store as often these days. But filtering through buckets (or online listings) of large numbers of coins can still be fun and lead to spotting good deals. So I think there is room in the hobby for nerd-like behavior (per your definition). I would argue the decline of the hobby is more due to competition from other similar hobbies (a generation ago you could collect stamps, coins, baseball cards, or rare books/comics - now you can collect beanie babies, Pokemon cards, NFTs, funko pops, action figures, etc.). I think stamps have suffered more than coins because stamp collecting has more of an aesthetic component (which has faced stronger competition) while coins have a historical element that is less well replicated by collecting newer things. This difference isn't obvious in the google trends graphs you posted but I believe is observable from looking at prices of stamps vs coins. I asked Nathan what coins he collects that are still tough to find, and he gave the example of this Yuan dynasty coin from 1350. I guess if you want to be a collector in 2023 you need to go hard. Arrk Mindmaster writes: I used to collect US coins from every denomination, year, mint, and variety (such as large and small date 1960 pennies). It was kind of like a treasure hunt, knowing you could find something in circulation that was actually more valuable than most people thought it was. I lost interest in the late 1980s sometime, when I found the volume of new coins dwarfed older coins. For example, for Lincoln pennies, they used to make a few million per year, then a few tens of millions. In the 80s, they started making about 5 BILLION each, and it started drowning out all of the old coins, which basically stayed the same value. This comment snapped some things into place for me; I collected coins as a kid in the 90s, and older coin collectors would talk as if you could spot some pretty rare things in your pocket change. But I had much worse luck, and it’s been years since I’ve even found a wheat cent in circulation (even when I was a kid this would happen occasionally). Maybe coin collecting is dying not just because we don’t use change, but because our change is less likely to have interesting coins in it. Another victim of mass money printing! The new state quarters sort of fix this, but other commenters express contempt for this. It feels like the transition between old myths (which one can enjoy) to the Marvel Cinematic Universe (which corporations are begging you to enjoy in a pre-approved way) - now that the Mint wants you to collect their coins, it feels kind of slavish to comply. Other people point out that the collecting of things other than stamps and coins is still going strong. Drethelin: Collecting has not in the slightest died out. People collect more things than ever, like sneakers, funko pops, vintage cars, guns, antique ceramics, anime figurines, magic cards, etc. Some people also brought up NFTs - are there lots of people who truly enjoy collecting NFTs, aren’t just in it for the investment value, and have kept up through the crypto bear market? 4. Comments Insisting That Sports Are Good Aris C writes: It's a little glib to dismiss sports as bad, isn't it? Athletes display extreme skill, sometimes transcendent. I don't think watching people push the limits of human ability is obviously bad. When I said sports were bad, I didn’t mean this as a final value judgment. I meant that, by our usual standards of entertainment, sports are bad. Imagine a sitcom which had several thousand episodes, each with the exact same plot (some people try to get a ball from one side of the court to the other). At some point, surely most people would stop watching! I appreciate the something something human spirit, and I’m happy to know that, somewhere in the world, sports are happening. It’s just the decision to actually watch them that confuses me. 5. Comments About Enjoying Things Vs. Building Identities Around Them Many people complained that some combination of me and/or Sam Kriss were denying that anyone can ever enjoy anything except as an attempt to “gain status”. I would answer first that yes, I think most behavior has some status component (although it may be a small component, mixed with genuine enjoyment). But also, it doesn’t seem mysterious that some people eg like Star Wars, or even love Star Wars. What seems mysterious to me is when this expresses itself as desire to buy thousands of dollars of figurines in the original boxes, or memorize the stats of every class of ship in the Imperial Navy, or something else which doesn’t seem very fun on its own merits. I’m not criticizing others from a place of invulnerability here. When I was ~14, I got really into Star Wars, and aside from reading all the Extended Universe books - some of which were genuinely very good - for about a year I spent all of my allowance and a good fraction of my free time obtaining Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing). My parents probably still have them somewhere. I cannot at all retrace what led me to do this, but I appreciate commenters’ less cynical explanations. For example, enchantingacacia writes: I think it's honestly sort of funny how non-nerds seem to genuinely not understand that a nerd's identity becomes about [thing] because they like it so much, not the other way around. Sometimes you encounter a thing—let's say it's Minecraft, because why not—and it's just such a positive experience for you that you take every possible opportunity to keep thinking about Minecraft, even when you're not playing. You collect every scrap of information you can find about Minecraft and you compose your own original Minecraft-related songs and you decorate your room with blocky little figurines. You get into a virtuous cycle where talking and thinking about Minecraft is so rewarding that you keep enjoying all these secondary activities long after you're bored of actually playing Minecraft itself. You look out for opportunities to meet people who'd enjoy talking about Minecraft with you and make a bunch of friends with whom you mostly talk about Minecraft, and your friends and family start seeing you as "the Minecraft guy" and they get you a Minecraft hoodie for Christmas cause they know it's a safe pick. This is the obvious and intuitive explanation! There's no need to get fake-deep about "ah, they got into Minecraft so they'd have something to construct their identity around": it explains nothing, and consistently makes incorrect predictions about the internal experiences of Minecraft nerds. It's only virtue is making people feel better about being annoyed by those weirdos who won't shut up about Minecraft. It's possibly that I have unusually low social motivation (genuinely, what does it mean to "construct your identity" and why is it something people would be this comically desperate to do?) and am typical-minding, but, uh, I wonder if there's any group closely associated with "nerds" who are also known for having low social motivation? I think it's a tad more likely that people like Kriss are typical-minding, and constructing elaborate social motivations for people who just like stuff regardless of what people like him think. This is a good comment which avoids buck-passing-style “I enjoy it because it’s fun” explanations. Along the same lines, odd anon writes: It is only among nerds that enthusiasm for something corresponds to learning more and more about it. That's the core element here. Non-nerds who like something do not feel any need to read up on it, to know more and more. Of course, the producers of content notice when their audience are nerds, and they start to produce content built more for those who obsessively learn every detail. Comics can start "rewarding" readers for noticing some obscure thing. A game series can have an elaborate continuity, or a zillion details to memorize. Content that either "leans into the fandom" or simply naturally has too much for non-nerds to easily pick up, can rapidly become nerd-only, thus solidifying boundaries. And sure, there are the personality correlations, attributes most nerds also have, including being STEM-y and lacking social skills. Combined, a nerd ended up being an unpopular thing to be. Ghatanathoah is less patient: Both Kriss' essay, and Scott's response to it, remind me of the "Evil Cannot Comprehend Good" trope from TV tropes, except replace "Evil" with "Very socially motivated people" and "Good" with "Less socially motivated people" (although honestly both sets have a lot of overlap). Both essays seem obsessed with finding some deep, social reason why hipsters and nerds behave the way they do, like the supervillain who is telling the hero that they are "Not So Different." They literally can't comprehend the idea that someone could actually like something, so they try desperately to find some way that liking things isn't something people actually do. People couldn't actually like Star Wars, sportsball, the MCU, or the Beatles, they must be liking them to achieve some social goal like forming an identity or seeking status! This is one of the two giant flawed assumptions that invalidates the theses of both articles (the other one, of course, is the assumption the the MCU is bad, when it is, in fact one of the human race's greatest artistic achievements*). If you assume that it is possible to like things for non-social reasons, or even in addition to social reasons, hipsters and nerds make much more sense. The reason that nerds like both popular stuff like the MCU, and less popular stuff like postage stamps is because they don't care about if something is popular, they care about if it fascinates them. Whether that thing is popular is orthogonal to how fascinating it is. That fascination makes them invest a lot of time and effort in it, which in turn makes it part of their identity. They weren't trying to find something to form and identity first and picking Star Wars, identity formation was just a side effect. Similarly, hipsters probably just get bored with things they see frequently and want to seek out new things to be interested in. Making obscure things part of their identity comes second, if at all. Also Ghatanathoah: Scott asks if its ever okay to build your identity around liking a thing. I would ask if it's ever okay not to? What's the alternative, building it around social status games or large nonselective identity groups? It seems to me that liking something isn't just a good thing to build your identity around, it's one of the best things to build it around. After all, unlike social status games, you can like something without forcing other people to not like it. This is a good question, well-phrased. I think the traditional answer is that you should build your identity around social relationships (I’m the son of X, husband of Y, friend of Z), career, and maybe a few hobbies. I agree with this as far as it goes, but it doesn’t work for a lot of practical tasks - I can’t get common ground with someone at a party or start a conversation by introducing myself as the son of X or husband of Y - most people just won’t know X or Y. Some people linked a Freddie de Boer post, Your Personality Has To Be Load-Bearing, which is generally good but I think has a similar problem. Obviously you should have a genuine and complex personality, but I worry a lot of people who talk about this will reject every specific aspect of personality because “it’s not, in itself, a full complex personality!”, but you can’t have a personality without building it out of specific aspects. A lot of people’s default personality, if they just do exactly what comes naturally and don’t put any effort into self-presentation or cultivation, is to browse Reddit and play video games. Most people realize this on some level and try to cultivate some personality beyond this, but I think that makes it extra unfair to say “Just use your natural true self!” The natural true self is exactly the boring thing we’re trying to get away from in favor of becoming a more interesting person. I’m trying to think if I have a personal answer to this. Part of my answer is the EA and rationalist communities. This has some downsides; I’m thinner-skinned about insults to these groups than I should be; some people might think I’m a fanatic. It also has some upsides; they embody real values I like, they try to make a difference in the world, they’re not consumer properties that make me feel like a corporation is pulling my strings. But my real answer is probably “I cheat by having a popular blog; this means you all know everything about me and I don’t have to fit my personality into a ten-second elevator pitch”. Maybe this is the traditional solution, from back when everyone knew everyone else in their community. It sure doesn’t feel adequate now, back when (non-bloggers) are constantly meeting strangers and having to communicate their identity to them quickly. My internal hierarchy of things it’s virtuous to build identity around, which is probably a weird class artifact and which I absolutely don’t consciously endorse, goes something like: Top-tier: Intellectual subfields, especially obscure ones or ones involving pure abstract math. If you can say “I’m really into trans-finite 8-dimensional Hoffdorf groups” and justify this with a discussion of how innately beautiful they are, you’ve got it made.
…where Sam fills in the northwest and southeast squares, then claims a correlation, draws a line, and points to high-status/deep-engagement as a single unified concept. But the southwest square could be “writes a wacky Shakespeare fanfiction, Romeo & Juliet II, in blank verse and period-appropriate language”, and the northeast square could be “publishes a dissertation on some irrelevant aspect of word frequency changes across English plays to prove something about linguistics”. And then having conflated these two things, he goes on to conflate a third thing, Shakespeare vs. Marvel. I’m not up to date on what goes on in academic literature departments, but Freddie de Boer says they’re increasingly offering “Spiderman Studies” classes in attempts to stay culturally relevant; probably Spiderman professors engage with Spiderman on the same deep level that Shakespeare professors engage with Shakespeare. If we made this a cube - high-status vs. low-status forms of engagement along one axis, Shakespeare vs. Spiderman along another axis, and deep vs. shallow engagement along the third - would anything be left of the “nerd” cluster as Sam describes it? I’m not sure. 2. Comments With Strong Opinions On The Definition Of Nerds, Geeks, Etc There were many of these. One common theme was that in the 70s, “nerd” was almost synonymous with “person who is only into unpopular things”, for example sci-fi, comics, and RPGs, all of which were unpopular in the 70s. Then those things became very popular, but the people who were interested in them still get called “nerds”. So now people like Kriss use “nerd” almost synonymously with “person who is only into popular things”. So we have a word which denotes either interest in unpopular things or interest in popular things, depending on who’s using it and when they last updated their lexicon. In the 70s, it was more reasonable to group “interested in math and computers” and “interested in sci-fi and RPGs” together, because both were unpopular and tended to involve the same group of socially maladept young men. Now math is still hard and unpopular; computers are hard in the sense that it’s tough to learn programming languages, but universally used and beloved; sci-fi and RPGs are very popular, and the typical sci-fi fan is closer to a socially-adept albeit “quirky” young woman. If words are hidden inferences, the inference represented by “nerd” - that sci-fi fandom, interest in math, interest in computers, maleness, poor social skills, and nonconformity with mainstream interests all go together - is now thoroughly false, dooming us to conversations like this one. Attempts to repurpose the several different words used to refer to the math/sci-fi/awkward/unpopular cluster to represent different aspects of its successor clusters have mostly failed. Sample comments from this section: Coagulopath writes: To me, being a nerd requires a degree of swimming against the cultural tide. It's weird and unpopular to be into trains, so the fact that you are indicates you have a bit of character (or are socially oblivious, which is also kind of endearing). The problem (and I think Kriss alludes to this) is that nerd stuff went mainstream in the past few decades. Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films. There's no longer any sense that nerds are the underdog. But what does it say about you when you wear a Star Wars shirt? You're pledging allegiance to the biggest, most popular club imaginable. Is that a brave stance? Those people always make me think "if you lived in the SW universe, you'd be on the side of the Empire". In general, I am creeped out by effusive public adoration for things that are near-universally loved. Like The Beatles. Or bacon. Or dogs. Or science (Neil DeGrasse Tyson's whole shtick). Regardless of how I feel about those things on the object level, there's no glory in joining a culture war when you're signing on to the winning side. Tolaughoftenandmuch writes: All this is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, Ghatanathoah writes: I also wouldn't say that nerd stuff only went mainstream in the last decade, it's not like the first 3 Star Wars movies were obscure arthouse pictures. I think the reason Marvel took off is just innovations in storytelling: movie producers finally figured out a way to adapt the gloriously arcane and convoluted lore of superhero comics in a way that could appeal to mainstream audiences in addition to nerds (much how George Lucas figured out how to get mainstream audiences to love the space operas nerds had been enjoying for decades before 1977). And Melvin writes: Comic book movies had always been pretty popular. Superman was the top grossing movie of 1979 despite coming out in 1978. Superman 2 was the second top grossing movie of 1981. Batman was the second top grossing movie of 1989. Batman Returns was the top grossing movie of 1992. Batman Forever was the top grossing movie of 1995. Spider-man was the third top grossing movie of 2002 (behind Lord of the Rings and Harry Potter movies). That's about all I can be bothered looking up right now but you get the idea, superhero movies have been popular since the 1970s. Kaitian writes: I think being a nerd requires being a bit socially clumsy about your interest, and talking or signalling about it in situations where most people don't expect it. So being a nerd about completely mainstream stuff like pop music or football is not possible, that's just fandom. Being a nerd about very well known and relatively well-respected stuff like classical music or birdwatching is rare, because most people who are classy enough to care about the thing in the first place are also classy enough to know when to shut up about it. But comics? Star trek? Power metal? They have fairly low barriers to entry *and* most people don't care about them, so there's plenty of opportunities to bring it up to people who don't want to hear about it. So that's why I think nerdery usually attaches itself to the typical targets. J.R. Leonard has as good a terminology proposal as anyone: I think what's missing is that Kriss uses "nerds" as his foil, but what he's talking about would better be described as fan culture. Deiseach teaches us the etymology of “geek”. The very distant etymology is from German gek, a relative of “cackle” → geck, a fool/madman (who was presumably cackling all the time). But this comes down to us through the early American institution of the geek show. From Wikipedia (cw: disturbing): Geek shows were an act in traveling carnivals and circuses of early America and were often part of a larger sideshow. The billed performer's act consisted of a single geek, who stood in the center ring to chase live chickens. It ended with the performer biting the chickens' heads off and swallowing them. The geek shows were often used as openers for what are commonly known as freak shows. It was a matter of pride among circus and carnival professionals not to have traveled with a troupe that included geeks. Geeks were often alcoholics or drug addicts, and paid with liquor – especially during Prohibition – or with narcotics. More obvious but I went surprisingly long without realizing it: “fan” (as in “sports fan”) is just short for fanatic. 3. Comments About Collecting The veteran collectors in the comments said that my theory (the Internet makes collecting too easy) was only a small part of the decline. The bigger part is that most coin collecting begins with the wonder of finding a rare coin in your change, and most stamp collecting begins with the wonder of finding a rare stamp on your mail, and the rise of credit cards and emails means people aren’t handling coins and stamps as much in their daily lives. Tom Metcalf writes: I'd guess many coin collectors got their start being patient enough to sort through change to see if they had e.g. a wheat cent or silver dime, but first of all, who pays with cash and gets change, and the chances of finding something collectible are orders of magnitude smaller than, say, the '90s. And stamp collectors would have started saving the stamps on mail sent to their house, but how frequently do you get stamped mail anymore? My 79-year old father goes to stamp shows, because one of his hobbies is to buy sheets of old but common unused stamps for less than face value. They are still valid postage, and then he uses them to personalize the stamps he puts on letters he sends to various people. And most of the other people at stamp shows are about his age. He does have some stamps he thinks are interesting that he's held onto, but the dealers at the stamp shows think they're common and uninteresting. So there's a decreasing number of stamps that might be "worth something" and a net loss of collectors in the hobby, and then every time a collector dies and his heirs have no interest in his collection and that many more stamps make their way to dealers who now have one less buyer. Too bad "sending paper letters with vintage but still valid stamps" never caught on with the hipsters. Art writes: The widespread adoption of email created a world where a letter is almost certainly junk mail or a bill. Nobody looks forward to hearing from a good friend from across the country now when picking up the day’s mail. If letters are not interesting why would stamps? The same for coins. Nobody uses cash, and getting a pile of coins with no significant value (inflation) is just an annoyance. These objects have passed into irrelevance. Still, it seems like some little pieces of joy and wonder have passed from our lives. Nathan Savir writes: I collect coins and I think the description of the hobby (and its putative death) isn't quite right. 1. Rare coins are in fact hard to find, even in today's internet world. They are usually sold in auctions, which might happen online, but still not that frequently. It's not unusual for examples some specific rare coin to be sold only once every few years. If the coin is also obscure, it may not be prohibitively expensive, so this kind of situation isn't the sole province of rich people. 2. One area of collecting is to get all the rare items. Another is to get all the minor varieties of a common item. These varieties may not be very rare, but it still takes a lot of effort to be able to distinguish them and to find them. Some collectors will obtain large numbers of relatively common coins and sort through and scrutinize them to try to identify interesting varieties. 3. An important part of collecting is getting good deals. This is surely a lot harder than it used to be because sellers can more easily figure out what things are worth and you won't find something grossly underpriced in a random antique store as often these days. But filtering through buckets (or online listings) of large numbers of coins can still be fun and lead to spotting good deals. So I think there is room in the hobby for nerd-like behavior (per your definition). I would argue the decline of the hobby is more due to competition from other similar hobbies (a generation ago you could collect stamps, coins, baseball cards, or rare books/comics - now you can collect beanie babies, Pokemon cards, NFTs, funko pops, action figures, etc.). I think stamps have suffered more than coins because stamp collecting has more of an aesthetic component (which has faced stronger competition) while coins have a historical element that is less well replicated by collecting newer things. This difference isn't obvious in the google trends graphs you posted but I believe is observable from looking at prices of stamps vs coins. I asked Nathan what coins he collects that are still tough to find, and he gave the example of this Yuan dynasty coin from 1350. I guess if you want to be a collector in 2023 you need to go hard. Arrk Mindmaster writes: I used to collect US coins from every denomination, year, mint, and variety (such as large and small date 1960 pennies). It was kind of like a treasure hunt, knowing you could find something in circulation that was actually more valuable than most people thought it was. I lost interest in the late 1980s sometime, when I found the volume of new coins dwarfed older coins. For example, for Lincoln pennies, they used to make a few million per year, then a few tens of millions. In the 80s, they started making about 5 BILLION each, and it started drowning out all of the old coins, which basically stayed the same value. This comment snapped some things into place for me; I collected coins as a kid in the 90s, and older coin collectors would talk as if you could spot some pretty rare things in your pocket change. But I had much worse luck, and it’s been years since I’ve even found a wheat cent in circulation (even when I was a kid this would happen occasionally). Maybe coin collecting is dying not just because we don’t use change, but because our change is less likely to have interesting coins in it. Another victim of mass money printing! The new state quarters sort of fix this, but other commenters express contempt for this. It feels like the transition between old myths (which one can enjoy) to the Marvel Cinematic Universe (which corporations are begging you to enjoy in a pre-approved way) - now that the Mint wants you to collect their coins, it feels kind of slavish to comply. Other people point out that the collecting of things other than stamps and coins is still going strong. Drethelin: Collecting has not in the slightest died out. People collect more things than ever, like sneakers, funko pops, vintage cars, guns, antique ceramics, anime figurines, magic cards, etc. Some people also brought up NFTs - are there lots of people who truly enjoy collecting NFTs, aren’t just in it for the investment value, and have kept up through the crypto bear market? 4. Comments Insisting That Sports Are Good Aris C writes: It's a little glib to dismiss sports as bad, isn't it? Athletes display extreme skill, sometimes transcendent. I don't think watching people push the limits of human ability is obviously bad. When I said sports were bad, I didn’t mean this as a final value judgment. I meant that, by our usual standards of entertainment, sports are bad. Imagine a sitcom which had several thousand episodes, each with the exact same plot (some people try to get a ball from one side of the court to the other). At some point, surely most people would stop watching! I appreciate the something something human spirit, and I’m happy to know that, somewhere in the world, sports are happening. It’s just the decision to actually watch them that confuses me. 5. Comments About Enjoying Things Vs. Building Identities Around Them Many people complained that some combination of me and/or Sam Kriss were denying that anyone can ever enjoy anything except as an attempt to “gain status”. I would answer first that yes, I think most behavior has some status component (although it may be a small component, mixed with genuine enjoyment). But also, it doesn’t seem mysterious that some people eg like Star Wars, or even love Star Wars. What seems mysterious to me is when this expresses itself as desire to buy thousands of dollars of figurines in the original boxes, or memorize the stats of every class of ship in the Imperial Navy, or something else which doesn’t seem very fun on its own merits. I’m not criticizing others from a place of invulnerability here. When I was ~14, I got really into Star Wars, and aside from reading all the Extended Universe books - some of which were genuinely very good - for about a year I spent all of my allowance and a good fraction of my free time obtaining Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing). My parents probably still have them somewhere. I cannot at all retrace what led me to do this, but I appreciate commenters’ less cynical explanations. For example, enchantingacacia writes: I think it's honestly sort of funny how non-nerds seem to genuinely not understand that a nerd's identity becomes about [thing] because they like it so much, not the other way around. Sometimes you encounter a thing—let's say it's Minecraft, because why not—and it's just such a positive experience for you that you take every possible opportunity to keep thinking about Minecraft, even when you're not playing. You collect every scrap of information you can find about Minecraft and you compose your own original Minecraft-related songs and you decorate your room with blocky little figurines. You get into a virtuous cycle where talking and thinking about Minecraft is so rewarding that you keep enjoying all these secondary activities long after you're bored of actually playing Minecraft itself. You look out for opportunities to meet people who'd enjoy talking about Minecraft with you and make a bunch of friends with whom you mostly talk about Minecraft, and your friends and family start seeing you as "the Minecraft guy" and they get you a Minecraft hoodie for Christmas cause they know it's a safe pick. This is the obvious and intuitive explanation! There's no need to get fake-deep about "ah, they got into Minecraft so they'd have something to construct their identity around": it explains nothing, and consistently makes incorrect predictions about the internal experiences of Minecraft nerds. It's only virtue is making people feel better about being annoyed by those weirdos who won't shut up about Minecraft. It's possibly that I have unusually low social motivation (genuinely, what does it mean to "construct your identity" and why is it something people would be this comically desperate to do?) and am typical-minding, but, uh, I wonder if there's any group closely associated with "nerds" who are also known for having low social motivation? I think it's a tad more likely that people like Kriss are typical-minding, and constructing elaborate social motivations for people who just like stuff regardless of what people like him think. This is a good comment which avoids buck-passing-style “I enjoy it because it’s fun” explanations. Along the same lines, odd anon writes: It is only among nerds that enthusiasm for something corresponds to learning more and more about it. That's the core element here. Non-nerds who like something do not feel any need to read up on it, to know more and more. Of course, the producers of content notice when their audience are nerds, and they start to produce content built more for those who obsessively learn every detail. Comics can start "rewarding" readers for noticing some obscure thing. A game series can have an elaborate continuity, or a zillion details to memorize. Content that either "leans into the fandom" or simply naturally has too much for non-nerds to easily pick up, can rapidly become nerd-only, thus solidifying boundaries. And sure, there are the personality correlations, attributes most nerds also have, including being STEM-y and lacking social skills. Combined, a nerd ended up being an unpopular thing to be. Ghatanathoah is less patient: Both Kriss' essay, and Scott's response to it, remind me of the "Evil Cannot Comprehend Good" trope from TV tropes, except replace "Evil" with "Very socially motivated people" and "Good" with "Less socially motivated people" (although honestly both sets have a lot of overlap). Both essays seem obsessed with finding some deep, social reason why hipsters and nerds behave the way they do, like the supervillain who is telling the hero that they are "Not So Different." They literally can't comprehend the idea that someone could actually like something, so they try desperately to find some way that liking things isn't something people actually do. People couldn't actually like Star Wars, sportsball, the MCU, or the Beatles, they must be liking them to achieve some social goal like forming an identity or seeking status! This is one of the two giant flawed assumptions that invalidates the theses of both articles (the other one, of course, is the assumption the the MCU is bad, when it is, in fact one of the human race's greatest artistic achievements*). If you assume that it is possible to like things for non-social reasons, or even in addition to social reasons, hipsters and nerds make much more sense. The reason that nerds like both popular stuff like the MCU, and less popular stuff like postage stamps is because they don't care about if something is popular, they care about if it fascinates them. Whether that thing is popular is orthogonal to how fascinating it is. That fascination makes them invest a lot of time and effort in it, which in turn makes it part of their identity. They weren't trying to find something to form and identity first and picking Star Wars, identity formation was just a side effect. Similarly, hipsters probably just get bored with things they see frequently and want to seek out new things to be interested in. Making obscure things part of their identity comes second, if at all. Also Ghatanathoah: Scott asks if its ever okay to build your identity around liking a thing. I would ask if it's ever okay not to? What's the alternative, building it around social status games or large nonselective identity groups? It seems to me that liking something isn't just a good thing to build your identity around, it's one of the best things to build it around. After all, unlike social status games, you can like something without forcing other people to not like it. This is a good question, well-phrased. I think the traditional answer is that you should build your identity around social relationships (I’m the son of X, husband of Y, friend of Z), career, and maybe a few hobbies. I agree with this as far as it goes, but it doesn’t work for a lot of practical tasks - I can’t get common ground with someone at a party or start a conversation by introducing myself as the son of X or husband of Y - most people just won’t know X or Y. Some people linked a Freddie de Boer post, Your Personality Has To Be Load-Bearing, which is generally good but I think has a similar problem. Obviously you should have a genuine and complex personality, but I worry a lot of people who talk about this will reject every specific aspect of personality because “it’s not, in itself, a full complex personality!”, but you can’t have a personality without building it out of specific aspects. A lot of people’s default personality, if they just do exactly what comes naturally and don’t put any effort into self-presentation or cultivation, is to browse Reddit and play video games. Most people realize this on some level and try to cultivate some personality beyond this, but I think that makes it extra unfair to say “Just use your natural true self!” The natural true self is exactly the boring thing we’re trying to get away from in favor of becoming a more interesting person. I’m trying to think if I have a personal answer to this. Part of my answer is the EA and rationalist communities. This has some downsides; I’m thinner-skinned about insults to these groups than I should be; some people might think I’m a fanatic. It also has some upsides; they embody real values I like, they try to make a difference in the world, they’re not consumer properties that make me feel like a corporation is pulling my strings. But my real answer is probably “I cheat by having a popular blog; this means you all know everything about me and I don’t have to fit my personality into a ten-second elevator pitch”. Maybe this is the traditional solution, from back when everyone knew everyone else in their community. It sure doesn’t feel adequate now, back when (non-bloggers) are constantly meeting strangers and having to communicate their identity to them quickly. My internal hierarchy of things it’s virtuous to build identity around, which is probably a weird class artifact and which I absolutely don’t consciously endorse, goes something like: Top-tier: Intellectual subfields, especially obscure ones or ones involving pure abstract math. If you can say “I’m really into trans-finite 8-dimensional Hoffdorf groups” and justify this with a discussion of how innately beautiful they are, you’ve got it made.
September 12, 2024 · Original source
29: Related: Richard Hanania interviews Scott Greer about the Greerhead Pledge. Greer is a far-right influencer with many followers. He urges them to take “the Greerhead Pledge”, which he changes occasionally, but it’s always about avoiding various forms of vice and insufficiently-right-wing-compatible content (currently it’s at “no weed, no rap, no Marvel movies, no tattoos”). I find this an interesting transitional step between the usual influencer fan clubs and the kinds of real communities (or even religions) that can produce real change. I can’t find any publicly available community of Greerheads, so I don’t know how real it is, but the concept has potential.
January 14, 2025 · Original source
Contra Hoel On Nerd Culture. When and why did “nerd movies” (eg Star Wars, Marvel) become so dominant?
January 16, 2026 · Original source
The variety of self-hating nerd are too many to number. There are the nerds who go into psychology to prove that EQ is a real thing and IQ merely its pale pathetic shadow. There are the nerds who become super-woke and talk about how reason and objectivity are forms of white supremacy culture. There are the nerds who obsess over “embodiment” and “somatic therapy” and accuse everyone else of “living in their heads”. There are the nerds who deflect by becoming really into neurodiversity - “the interesting thing about my brain isn’t that I’m ‘smart’ or ‘rational’, it’s that I’m ADHDtistic, which is actually a weakness . . . but also secretly a strength!” There are the nerds who flirt with fascism because it idolizes men of action, and the nerds who convert to Christianity because it idolizes men of faith. There are the nerds who get really into Seeing Like A State, and how being into rationality and metrics and numbers is soooooo High Modernist, but as a Kegan Level Five Avatar they are far beyond such petty concerns. There are the nerds who redefine “nerd” as “person who likes Marvel movies” - having successfully gerrymandered themselves outside the category, they can go back to their impeccably-accurate statisticsblogging on educational outcomes, or their deep dives into anthropology and medieval mysticism, all while casting about them imprecations that of course nerds are loathsome scum who deserve to be bullied.
MidJourney

MidJourney is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between September 12, 2022 and July 08, 2025. The archive places it in contexts such as "MidJourney announced July 2022"; "MidJourney: Forgot to test this one!"; "random nobody startups came out with ... MidJourney". It most often appears alongside GPT, Scott, AI.

Article page
MidJourney
Mention count
4
Issue count
4
First seen
September 12, 2022
Last seen
July 08, 2025
September 12, 2022 · Original source
MidJourney announced July 2022.
MidJourney: Forgot to test this one!
March 01, 2023 · Original source
DeepMind thought they were establishing a lead in 2008, but OpenAI has caught up to them. OpenAI thought they were establishing a lead the past two years, but a few months after they came out with GPT, at least Google, Facebook, and Anthropic had comparable large language models; a few months after they came out with DALL-E, random nobody startups came out with StableDiffusion and MidJourney. None of this research has established a commanding lead, it’s just moved everyone forward together and burned timelines for no reason.
August 30, 2023 · Original source
Midjourney 5 had not come out, and so we were using 4 to generate some characters for our app.
Then Midjourney 5 came out and started behaving a lot better. Feet were pretty trivial to generate (and hands reliably had 5 fingers) and the excitement of seeing them quickly wore off.
July 08, 2025 · Original source
One of the questions on the 2023 - 2024 ACX prediction contest was whether any AI would win the bet by the end of 2023. In order to resolve the question, Edwin and his Surge team returned to the image mines in January 2024. They checked DALL-E3 and Midjourney; I’m including only the pictures from DALL-E3, which did better. Here they are:
modafinil

modafinil is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between January 25, 2021 and February 20, 2025. The archive places it in contexts such as "I give up on amphetamines and start looking at Ritalin, modafinil, or other options"; "Zembrin beats out modafinil to make it highest on the list"; "Zembrin outperformed modafinil and phenibut on the survey". It most often appears alongside Adderall, ADHD, modafinil.

Article page
modafinil
Mention count
4
Issue count
4
First seen
January 25, 2021
Last seen
February 20, 2025
January 25, 2021 · Original source
When I treat ADHD with amphetamines, I usually start with Adderall/extended release Adderall, even though realistically Dexedrine would probably be an equally good or better choice. If it's not working very well or there are too many side effects, I switch to Dexedrine/extended release Dexedrine. If Dexedrine doesn't work because it seems too strong or the patient "crashes" too hard afterwards, or if I'm worried the patient is at risk of addiction, I will try Vyvanse (or some other solution to stimulant “crashes”); if Dexedrine works less well than Adderall and I am very confused and the patient is in an experimenting kind of mood, I might try Evekeo. If none of these work, a braver person than I am might try Desoxyn. As for me, I give up on amphetamines and start looking at Ritalin, modafinil, or other options.
April 28, 2021 · Original source
But I and many other people have had good results with Zembrin, a concentrated extract of kanna advertised for low mood and anxiety. So I asked respondents to specify whether their kanna was Zembrin or something else. Of 37 kanna users, 20 used Zembrin and 17 used something else. The subgroup who used Zembrin reported a mean effectiveness of 6.88, which beats out modafinil to make it highest on the list. After ad hoc Bayesian adjustment, it was 6.72, second only to modafinil as the second most effective nootropic on the list. This really excites me - I've felt like Zembrin was special for a while, and this is the only case of a newer nootropic on the survey beating the mainstays. And it's a really unexpected victory. The top eight substances in the list are all either stimulants, addictive, illegal in the US, or all three. Zembrin is none of those, and it beats them all.
I'm not sure. SSRIs are very effective for a lot of people. But Zembrin outperformed modafinil and phenibut on the survey. I have never heard even the most extreme fan of SSRIs (possibly me, honestly) claim people like them more than modafinil or phenibut. So this is either a bias (people think it's cool to be taking a new experimental plant, but don't like taking prescription medications with a bad reputation), or else Zembrin is either not an SSRI, or not just an SSRI. Of note, there are ways to prepare kanna (the plant Zembrin comes from) that make it kind of a recreational drug of abuse, though not a very addictive one. This suggests it has something more than just SSRI activity.
Sublingual Modafinil Is Not Very Interesting
November 16, 2022 · Original source
Here the detectives on r/NootropicsDepot recognized it as their company’s old brand of adrafinil7. Adrafinil is a prodrug of modafinil, an unusual stimulant-like drug. That is, your body metabolizes adrafinil and turns it into modafinil after you take it.
So was SBF effectively on modafinil? Seems likely - many traders are. I won’t lie - modafinil is a good stimulant, during medical residency some doctors (including me) would use it to stay alert through the night shift. It’s not any better than Adderall or anything, just a bit different and easier to get.
Does it affect attitudes to risk? Hopefully you can already predict my answer to that question: all dopaminergics affect attitude to risk in complicated ways we don’t really understand, but for most people these effects will be too small to notice. There’s one case report of modafinil causing pathological gambling, and various contrived studies where neuroscientists investigate how modafinil shifts some technical parameter in a risk curve; these kinds of studies often don’t replicate. I think you can really just stick to your prior of “all dopaminergics affect risk curves in ways we don’t understand, but it’s usually fine when your job doesn’t require perfectly-tuned risk awareness”.
February 20, 2025 · Original source
St. Clare was so upset about believing false things during her dreams that she took modafinil every night rather than sleep. She completed several impressive programming projects before passing away of sleep deprivation after three weeks; she was declared a martyr by Pope Raymond II.
Novo Nordisk

Novo Nordisk is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between November 24, 2022 and March 12, 2025. The archive places it in contexts such as "accusing Novo Nordisk of 'charg[ing] people more for the same drug because of their obesity'"; "Novo Nordisk’s competitor Eli Lilly owns a closely related molecule"; "Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month". It most often appears alongside FDA, Novo Nordisk, Eli Lilly.

Article page
Novo Nordisk
Mention count
4
Issue count
4
First seen
November 24, 2022
Last seen
March 12, 2025
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.
Sixth, this post focuses on GLP-1 agonists, which makes sense, because those drugs are starting to have an impact today. But the Morgan Stanley report also notes that amylin analogue cagrilintide may be approved for weight loss as soon as 2025. This drug has a completely different mechanism than semaglutide, but likely offers similar weight loss benefits. The crazy thing is that the weight loss benefits stack. So Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide, and hopes to offer a ~30% average weight loss. This is roughly double what semaglutide offers, and is getting closer to bariatric surgery efficacy.
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
August 22, 2024 · Original source
They say it’s through the same factories that make the official version for Big Pharma. If I understand the situation, nameless Chinese factories1 make the chemical itself, and Novo Nordisk (the pharmaceutical company that owns the official patent) does some fancy encapsulation work at their own plants. But they have a permanent capacity problem because of logistical and regulatory issues, so the nameless Chinese factories sell the extra to the compounding pharmacies on the side.
Don’t get me wrong, this does probably take a big chunk out of Novo Nordisk’s profits. But Novo Nordisk’s stock price currently looks like this:
…and they’re now the most valuable company in Europe. So they can probably eat the loss. What happens when the shortage ends? Compounding pharmacies are only allowed to do this because of a law that suspends some drug regulations during a “shortage”, ie when the drug is on the FDA’s drug shortage list. At some point, Novo Nordisk will build enough factories to meet capacity and there won’t be a shortage anymore. What then? Will the fun be over? Will GLP-1 agonists go back to costing $1,200/month again? Will most of the current users have to stop the drug and regain the lost weight? This would make tens of thousands of people really mad. I don’t know if the FDA has the guts to offend that many people. Their style is more to crush drugs before they ever come out, before anyone knows what they’re missing. During COVID, the DEA said that telemedicine was allowed to be cheap and convenient so patients could get care during lockdown. After the pandemic died down, they tried making it hard and expensive again, but so many patients protested that they backed off. The uproar we’ll get if the FDA tries to make GLP-1 drugs expensive again will make that one look like a tempest in a teapot. But Big Pharma will be even angrier if they don’t. And besides, they can’t keep the drug on their shortage list if everyone knows there’s no shortage. I really don’t know what will happen, and I don’t envy whichever FDA official is in charge of setting a policy on this. I did see one proposed solution somewhere or other (sorry if it’s yours and I’m not crediting you). Compound pharmacies are always allowed to make compounded medications for specific patients who have a “medical necessity” for a non-FDA-approved product. So in theory, you could try something like: Tell the patient to say that Ozempic causes them nausea.
March 12, 2025 · Original source
But the compounders aren’t the only ones boxing clever. Novo Nordisk and Eli Lilly, the pharma companies behind semaglutide and tirzepatide respectively, have opened consumer-facing businesses about halfway between a traditional doctor’s appointment and the telehealth/compounder model that’s getting banned. So for example, Lilly Direct offers to “find you a doctor” (I think this means you do telehealth with an Eli Lilly stooge who always gives you the meds you want) and “get medications delivered directly to you”. The price depends on dose, but an average dose would be about $500 - so about halfway between the cheap compounding price and the usual insurance price. Not bad.
Some people are stocking up. GLP-1 drugs keep pretty well in a fridge for at least a year. If you sign up for four GLP-1 telehealth compounding companies simultaneously and order three months from each, then you can get twelve months of medication. Maybe in twelve months the FDA will change their mind, or the pharmacies’ insane legal strategies will pay off, or Trump will invade Denmark over Greenland and seize the Novo Nordisk patents as spoils of war, or someone will finally figure out a diet that works.
Prozac

Prozac is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between March 31, 2021 and May 31, 2023. The archive places it in contexts such as "20 mg of paroxetine (Paxil) or fluoxetine (Prozac)"; "dose equivalent to 30 mg of fluoxetine (aka Prozac)"; "Semaglutide is now as searched-for on Google as Prozac". It most often appears alongside FDA, SSRIs, ACE inhibitors.

Article page
Prozac
Mention count
4
Issue count
4
First seen
March 31, 2021
Last seen
May 31, 2023
March 31, 2021 · Original source
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
They find antidepressants are most effective (the first graph, marked "response") at doses equivalent to 30 mg of fluoxetine (aka Prozac; 1 fluoxetine-equivalent = 5 of the imipramine-equivalents the other study uses). If that were true, the most effective dose of every SSRI would be:
Overall, I think there we're on shaky ground saying that any antidepressant works better at high doses than low-to-medium ones of about 30 mg fluoxetine equivalent. But despite what the FDA says, prescribing high doses of Lexapro probably isn't any worse than prescribing high doses of any other antidepressant, and it might even be better. In the rare cases where I think it might help, I plan to continue prescribing doses of up to 30 mg without worrying at all, and up to 40 mg while worrying only slightly.
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
December 07, 2022 · Original source
"Hello, this is Dr. Alexander. My patient Jane Smith says you suddenly won't cover their Prozac which they've been on for ten years, I was hoping that was a clerical error and you could - "
"I HATE Y - oh! You're a human! This is Dr. Alexander. My patient Jane Smith says you suddenly won't cover their Prozac which they've been on for ten years, I was hoping that was a clerical error and you could fix it."
"You stopped covering my patient's Prozac and won't tell me why, and your representatives keep saying that they need my Medical Assessment Number before they can solve my problem but there's no such thing."
May 31, 2023 · Original source
SSRI antidepressants like Prozac were first developed in the 1980s and 1990s. The first round of studies, sponsored by pharmaceutical companies, showed they worked great! But skeptics found substantial bias in these early trials; several later analyses that corrected for this all found effect sizes (compared to placebo) of only 0.30.
UberEats

UberEats is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between February 26, 2021 and April 22, 2025. The archive places it in contexts such as "It's just a link to their UberEats/DoorDash pages"; "every time I order food from UberEats"; "UberEats drivers $7 for the same service". It most often appears alongside California, China, COVID.

Article page
UberEats
Mention count
4
Issue count
4
First seen
February 26, 2021
Last seen
April 22, 2025
February 26, 2021 · Original source
Their website has ten different accessibility options, including "pause animations" and "dyslexia friendly", hidden in an unobtrusive corner menu. This is great. It seems to be courtesy of a site called UserWay, so check them out if you like user-readable websites. This is the most accessible site I have ever seen, which makes it ironic that it has no actual content. It's just a link to their UberEats/DoorDash pages, all of which are inaccessible as usual.
August 30, 2021 · Original source
And every time I order food from UberEats, I get a menu like this:
I find I usually click the third box on both. I want to tip generously, but giving the maximum possible tip seems profligate. Surely the third box is the right compromise. I recently noticed that this is insane. For a $35 meal, I’m giving GrubHub drivers $3 and UberEats drivers $7 for the same service (or maybe there’s some difference between their services which makes UberEats suggest the higher tip - but if there is, I don’t know about it and it doesn’t affect my decision). Again, this is Behavioral Economics 101 - in particular, one of the many biases lumped together under menu effects. Instead of being a rational economic actor who values food delivery at a certain price, I’m trying to be a third-box-of-four kind of guy. That means that whoever is in charge of this menu has lots of power over the specific dollar amount I give. Not infinite power - if the third box said $1000 I would notice and refuse. But enough power that “nudging” seems like a fair description. Nobody believes studies anymore, which is fair. I trust in a salvageable core of behavioral economics and “nudgenomics” because I can feel in my bones that they’re true for me and the people around me. Let’s move on to Hreha’s article and see if we can square it with my belief in a “salvageable core”. II. Yechaim’s Historical Detective Story Hreha writes: The biggest replication failures relate to the field's most important idea: loss aversion. To be honest, this was a finding that I lost faith in well before the most recent revelations (from 2018-2020). Why? Because I've run studies looking at its impact in the real world—especially in marketing campaigns. If you read anything about this body of research, you'll get the idea that losses are such powerful motivators that they'll turn otherwise uninterested customers into enthusiastic purchasers. The truth of the matter is that losses and benefits are equally effective in driving conversion. In fact, in many circumstances, losses are actually *worse* at driving results. Why? Because loss-focused messaging often comes across as gimmicky and spammy. It makes you, the advertiser, look desperate. It makes you seem untrustworthy, and trust is the foundation of sales, conversion, and retention. "So is loss aversion completely bogus?" Not quite. It turns out that loss aversion does exist, but only for large losses. This makes sense. We *should* be particularly wary of decisions that can wipe us out. That's not a so-called "cognitive bias". It's not irrational. In fact, it's completely sensical. If a decision can destroy you and/or your family, it's sane to be cautious. "So when did we discover that loss aversion exists only for large losses?" Well, actually, it looks like Kahneman and Tversky, winners of the Nobel Prize in Economics, knew about this unfortunate fact when they were developing Prospect Theory—their grand theory with loss aversion at its center. Unfortunately, the findings rebutting their view of loss aversion were carefully omitted from their papers, and other findings that went against their model were misrepresented so that they would instead support their pet theory. In short: any data that didn't fit Prospect Theory was dismissed or distorted. I don't know what you'd call this behavior... but it's not science. This shady behavior by the two titans of the field was brought to light in a paper published in 2018: "Acceptable Losses: The Debatable Origins of Loss Aversion". I encourage you to read the paper. It's shocking. This line from the abstract sums things up pretty well: "...the early studies of utility functions have shown that while very large losses are overweighted, smaller losses are often not. In addition, the findings of some of these studies have been systematically misrepresented to reflect loss aversion, though they did not find it." When the two biggest scientists in your field are accused of "systemic misrepresentation", you know you've got a serious problem. Which leads us to another paper, published in 2018, entitled "The Loss of Loss Aversion: Will It Loom Larger Than Its Gain?". The paper's authors did a comprehensive review of the loss aversion literature and came to the following conclusion: "current evidence does not support that losses, on balance, tend to be any more impactful than gains." Yikes. But given the questionable origins of the field, it's not surprising that its foundational finding is *also* dubious. If loss aversion can't be trusted, then no other idea in the field can be trusted. This argument relies on two papers - Yechaim’s Acceptable Losses and Gal & Rucker’s Loss Of Loss Aversion. Yechaim’s paper is a historical detective story. It looks at how Kahneman and Tversky first “discovered” and popularized the idea of loss aversion from earlier 1950s and 1960s research. It concludes they did a bad job summarizing this earlier research; looked at carefully, it doesn’t support the strong conclusions they drew. From one perspective, nobody should care about this. All the 1950s and 1960s research was terrible - one of the most important studies it discusses had n = 7. Since then, we’ve had much more rigorous studies of tens of thousands of people. All that hinges on Yechaim’s paper is whether Kahneman and Tversky were personally bad people. Hreha thinks they were. He calls their behavior “shady”, “shocking”, and says they “systematically misrepresented findings to support their pet theory…I don't know what you'd call this behavior... but it's not science.” Again, nothing important really hinges on this, but I feel like fighting about it, so let’s look deeper anyway. Here’s how Yechaim summarizes his accusation against K&T: In addition, the results of several studies seem to have been misrepresented by Fishburn and Kochenberger (1979) and Kahneman and Tversky (1979). Galenter and Pliner (1974) were wrongly cited as showing loss aversion, whereas, in fact, they did not observe an asymmetry in the pleasantness ratings of gains and losses. Likewise, in Green (1963), the results were argued to show loss aversion, even though this study did not involve any losses. In addition, the objective outcomes for some of the participants in Grayson (1960) were transformed by Fishburn and Kochenberger (1979) so as to better support a model assuming different curvatures for gains and losses (see Table 1). Finally, studies showing no loss aversion or suggesting aversion to large losses were not cited in Fishburn and Kochenberger (1979) or in Kahneman and Tversky (1979). Yechaim bases his argument on three sets of early studies of loss aversion: Galenter and Plinter (1974), Fishburn and Kochenberger’s review (1979) and miscellaneous others. —Galenter and Plinter— is actually really neat! It explores “cross-modal” perceptions of gains versus losses. That is, if you ask how much a certain loss hurt, people will probably just say something like “I dunno, a little?” and then it will be hard to turn that into a p-value. G&P solve this by making people listen to loud noises, and asking questions like “is the difference between how much loss A and loss B hurt greater or lesser than the difference between the volume of noise 1 and noise 2?” The idea is that the brain uses a bunch of weird non-numerical scales for everything, and we understand its weird-non-numerical scale for noise volume pretty well, and so maybe we can compare it to how people think about gains or losses. I don’t know why people in 1974 were doing anything this complicated instead of inventing the basic theory of loss aversion the way Kahneman and Tversky would five years later, but here we are. Anyway, Yechaim concludes that this study failed to find loss aversion: Summing up their findings, Galenter and Pliner (1974) reported as follows: “We now turn to the question of the possible asymmetry of the positive and negative limbs of the utility function. On the basis of intuition and anecdote, one would expect the negative limb of the utility function to decrease more sharply than the positive limb increases... what we have observed if anything is an asymmetry of much less magnitude than would have been expected ... the curvature of the function does not change in going from positive to negative” (p. 75). Thus, our search for the historical foundations of loss aversion turns into a dead end on this particular branch: Galenter and Pliner (1974) did not observe such an asymmetry; and their study was quoted erroneously [by Kahneman and Tversky]. I looked for the full text of Galenter and Pliner, but could not find it. I was however able to find the first two pages, including the abstract. The way Galenter and Pliner summarize their own research is: Cross-modality matching of hypothetical increments of money against loudness recover the previously proposed exponent of the utility function for money within a few percent. Similar cross-modality matching experiments for decrements give a disutility exponent of 0.59, larger than the utility exponent for increments. This disutility exponent was checked by an additional cross-modality matching experiment against the disutility of drinking various concentrations of a bitter solution. The parameter estimated in this fashion was 0.63. If I understand the bolded part right, the abstract seems to be saying that they did find loss aversion! I was also able to find the Google Books listing for the book that the study was published in. Its summary is: Three experiments were conducted in which monetary increments and decrements were matched to either the loudness of a tone or the bitterness of various concentrations of sucrose octa-acetate. An additional experiment involving ratio estimates of monetary loss is also reported. Results confirm that the utility function for both monetary increments and decrements is a power function with exponents less than one. The data further suggest that the exponent of the disutility function is larger than that of the utility function, i.e., the rate of change of 'unhappiness' caused by monetary losses is greater than the comparable rate of 'happiness' produced by monetary gains. (Author). Again, the way the book is summarized (apparently by the author) says this study does prove loss aversion. Without being able to access the full study, I’m not sure what’s going on. Possibly the study found loss aversion, but it was less than expected? Still, I feel like Yechaim should have mentioned this. At the very least, it decreases Kahneman and Tversky’s crime from “lied about a study to support their pet theory” to “credulously believed the authors’ own summary of their results and didn’t dig deeper”. But also, why did the authors believe their study showed loss aversion? Why does Yechaim disagree? Without being able to access the full paper, I’m not sure. —Green 1963— is the second study that Yechaim accuses K&T of misrepresenting. Here’s how K&T cite this study in their paper: It is of interest that the main properties ascribed to the value function have been observed in a detailed analysis of von Neumann-Morgenstern utility functions for changes of wealth (Fishburn and Kochenberger [14]). The functions had been obtained from thirty decision makers in various fields of business, in five independent studies [5, 18, 19, 21, 40]. Most utility functions for gains were concave, most functions for losses were convex, and only three individuals exhibited risk aversion for both gains and losses. With a single exception, utility functions were considerably steeper for losses than for gains. Green 1963 is footnote 19. So K&T don’t even mention it by name. They mention it as one of several studies that a review article called Fishburn and Kochenberger analyzes. F&K are reviewing a bunch of studies of executives. In each study, a very small number of executives (usually about 5-10 per study) make a hypothetical business decision comparing gains and losses, for example: Suppose your company is being sued for patent infringement. Your lawyer’s best judgement is that your chances of winning the suit are 50–50; if you win, you will lose nothing, but if you lose, it will cost the company $1,000,000. Your opponent has offered to settle out of court for $200,000. Would you fight or settle? Then they ask the same question with a bunch of other numbers, and plot implied utility functions for each executive based on the answer. Green is one of these five studies, and it does superficially find loss aversion. But Fishburn and Kochenberger have done something weird. They argue that “loss” and “gain” aren’t necessarily objective, and usually correspond to “loss relative to some reference frame” (so far, so good). In order to figure out where the reference frame is, they assume that the neutral point is wherever “something unusual happens to the individual’s utility function” (F&K’s words). So they shift the zero point separating losses and gains to wherever the utility function looks most interesting! After doing this, they find “loss aversion”, ie the utility curve changes its slope at the transition between the loss side and the gain side. But since the transition was deliberately shifted to wherever the utility curve changed slope, this is almost tautological. It isn’t quite tautological: it’s interesting that most of the utility curves had a sharp transition zone, and it’s interesting that the transition was in the direction of loss-aversion rather than gain-seeking. But it’s tautological enough to be embarrassing. Still, this is Fishburn and Kochenberger’s embarrassment, not Kahneman and Tversky’s. And Fishburn and Kochenberger included this study in their review alongside several other studies that didn’t do this to the same degree. Kahneman and Tversky just cited the review article. I don’t think citing a review article that does weird things to a study really qualifies as “systematic misrepresentation.” I guess I’m having a hard time figuring out how angry to be, because everything about Fishburn and Kochenberger is terrible. The average study in F&K includes results from 5-10 executives. But the studies are pretty open about the fact that they interviewed more executives than this, threw away the ones who gave boring answers, and just published results from the interesting ones. Then they moved the axes to wherever looked most interesting. Then they used all this to draw sweeping generalizations about human behavior. Then F&K combined five studies that did this into a review article, without protesting any of it. And then K&T cited the review article, again without protesting. I have to imagine that all of this was normal by the standards of the time. I have looked up all these people and they were all esteemed scientists in their own day. And I believe the evidence shows K&T summarized F&K faithfully. Shouldn’t they have avoided citing F&K at all? Seems like the same kind of question as “Shouldn’t Pythagoras have published his theorem in a peer-reviewed journal, instead of moving to Italy, starting a cult, and exposing his thigh at the Olympic Games as part of a scheme to convince people he was the god Apollo?” Yes, but the past was a weird place. As best I can tell, K&T’s citation of G&P agrees with the authors’ own assessment of their results. Their citation of F&K agrees with the reviewers’ assessment and with a charitable reading of most of the studies involved, although those studies are terrible in many ways which are obvious to modern readers. I would urge people interested in the whodunit question to read Kahneman and Tversky’s original paper. I think it paints the picture of a team very interested in their own results and in theory, and citing other people only incidentally, and in accordance with the scientific standards of their time. I don’t feel a need to tar them as “misrepresenters”. III. Okay, But Is Loss Aversion Real? Remember, all that is about the personal deficiencies of Kahneman and Tversky. Realistically there have been hundreds of much better studies on loss aversion in the forty years since they wrote their article, so we should be looking at those. Here Hreha cites Gal & Rucker: The Loss Of Loss Aversion: Will It Loom Larger Than Its Gain? It’s a great 2018 paper that looks at recent evidence and concludes that loss aversion doesn’t exist. But it’s a very specific, interesting type of nonexistence, which I think the Hreha article fails to capture. G&R are happy to admit that in many, many cases, people behave in loss-averse ways, including most of the classic examples given by Kahneman and Tversky. They just think that this is because of other cognitive biases, not a specific cognitive bias called “loss aversion”. They especially emphasize Status Quo Bias and the Endowment Effect. Status Quo Bias is where you prefer inaction to action. Suppose you ask someone “Would you bet on a coin flip, where you get $60 if heads and lose $40 if tails?”. They say no. This deviates from rational expectations, and one way to think of this is loss aversion; the prospect of losing $40 feels “bigger” than the prospect of gaining $60. But another way to think of it is as a bias towards inaction - all else being equal, people prefer not to make bets, and you’d need a higher payoff to overcome their inertia. Endowment Effect is where you value something you already have more than something you don’t. Suppose someone would pay $5 to prevent their coffee mug from being taken away from them, but (in an alternative universe where they lack a coffee mug) would only pay $3 to buy one. You can think of this as loss aversion (the grief of losing a coffee mug feels “bigger” than the joy of gaining one). Or you can think of it as endowment (once you have the coffee mug, it’s yours and you feel like defending it). These are really fine distinctions; I had to read the section a few times before the difference between loss aversion and endowment effect really made sense to me. Kahneman and Tversky just sort of threw all all this stuff out and saw what stuck and didn’t necessarily try super hard to make sure none of the biases they discovered were entirely explainable as combinations of some of the others. G&R think maybe loss aversion is. They do some clever work setting up situations that test loss aversion but not status quo or endowment - for example, offering a risky bet vs. a safer bet. Here they find no evidence for loss aversion as a separate force from the other two biases. Somewhere in this process, they did an experiment where they gave participants a quarter minted in Denver and asked them if they wanted to exchange it for a quarter minted in Philadelphia. 60% of people very reasonably didn’t care, but another 35% had grown attached to their Denver quarter, with only 5% actively seeking the novelty of Philadelphia. Psychology is weird. I understand why some people would summarize this paper as “loss aversion doesn’t exist”. But it’s very different from “power posing doesn’t exist” or “stereotype threat doesn’t exist”, where it was found that the effect people were trying to study just didn’t happen, and all the studies saying it did were because of p-hacking or publication bias or something. People are very often averse to losses. This paper just argues that this isn’t caused by a specific “loss aversion” force. It’s caused by other forces which are not exactly loss aversion. We could compare it to centrifugal force in physics: real, but not fundamental. Also, you can’t use this paper to argue that “behavioral economics is dead”. At best, the paper proves that loss aversion is better explained by other behavioral economic concepts. But you can’t get rid of behavioral econ entirely! The stuff you have to explain is still there! It’s just a question of which parts of behavioral econ you use to explain it. Complicating this even further is Mrkva et al, Loss Aversion Has Moderators, But Reports Of Its Death Are Greatly Exaggerated (h/t Alex Imas, who has a great Twitter thread about this). This is an even newer paper, 2019, which argues that Gal and Rucker are wrong, and loss aversion does have an independent existence as a real force. There are many things to like about this paper. Previous criticisms of loss aversion argue that most experiments are performed on undergrads, who are so poor that even small amounts of money might have unusual emotional meaning. Mrkva collects a sample of thousands of millionaires (!) and demonstrates that they show loss aversion for sums of money as small as $20. On the other hand, I’m not sure they’re quite as careful as G&R at ruling out every other possible bias (although I don’t have a great understanding of where the borders between biases are and I can’t say this for sure). The main point I want to make is that all the scientists in this debate seem smart, thoughtful, and impressive. This isn’t like social priming experiments where one person says a crazy thing, nobody ever replicates it at scale, and as soon as someone tries the whole thing collapses. These have been replicated hundreds of times, with the remaining arguments being complicated semantic and philosophical ones about how to distinguish one theory from a very slightly different theory. If that takes replicating your result on a sample of thousands of millionaires, people will gather a sample of thousands of millionaires and get busy on the replication. Just overall really impressive work. I don’t feel qualified to take a side in the G&R vs. Mkrva debate, but both teams make me really happy that there are smart and careful people considering these questions. And this is just a drop in the bucket. Alex Imas also links Replicating patterns of prospect theory for decision under risk, which says: Though substantial evidence supports prospect theory, many presumed canonical theories have drawn scrutiny for recent replication failures. In response, we directly test the original methods in a multinational study (n = 4,098 participants, 19 countries, 13 languages), adjusting only for current and local currencies while requiring all participants to respond to all items. The results replicated for 94% of items, with some attenuation. Twelve of 13 theoretical contrasts replicated, with 100% replication in some countries. Heterogeneity between countries and intra-individual variation highlight meaningful avenues for future theorizing and applications. We conclude that the empirical foundations for prospect theory replicate beyond any reasonable thresholds. Beyond any reasonable thresholds! IV. Do Nudges Work? or, How Small Is Small? Continuing through the Hreha article: For a number of years, I've been beating the anti-nudge drum. Since 2011, I've been running behavioral experiments in the wild, and have always been struck by how weak nudges tend to be. In my experience, nudges usually fail to have *any* recognizable impact at all. This is supported by a paper that was recently published by a couple of researchers from UC Berkeley. They looked at the results of 126 randomized controlled trials run by two "nudge units" here in the United States. I want you to guess how large of an impact these nudges had on average... 30%? 20%? 10%? 5%? 3%? 1.5%? 1%? 0%? If you said 1.5%, you'd be right (the actual number is 1.4%, but if I had written that out you would have chosen it because of its specificity). According to the academic papers these nudges were based upon, these nudges should have had an average impact of 8.7%. But, as you probably understand by now, behavioral economics is not a particularly trustworthy field. I actually emailed the authors of this paper, and they thought the ~1% effect size of these interventions was something to be applauded—especially if the intervention was cheap & easy. Unfortunately, no intervention is truly cheap or easy. Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. Uber infamously had a team of behavioral economists working on its product, trying to “nudge” people in the right direction. Relatedly, Uber makes $10 billion in yearly revenue. If they can “nudge” people to spend 1% more, that’s $100 million. That’s not much relative to revenue, but it’s a lot in absolute terms. In particular, it pays the salary of a lot of behavioral economists. If you can hire 10 behavioral economists for $100,000 a year and make $100 million, that’s $99 million in profit. Or what if you’re a government agency, trying to nudge people to do prosocial things? There are about 90 million eligible Americans who haven’t gotten their COVID vaccine, and although some of them are hard-core conspiracy theorists, others are just lazy or nervous or feel safe already. (source) Whoever decided on that grocery gift card scheme was nudging, whether or not they have an economics degree - and apparently they were pretty good at it. If some sort of behavioral econ campaign can convince 1.5% of those 90 million Americans to get their vaccines, that’s 1.4 million more vaccinations and, under reasonable assumptions, maybe a few thousand lives saved. Hreha says that: Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. This depends on scale! 1% of a small number isn’t worth it! 1% of a big number is very worth it, especially if that big number is a number of lives! A few caveats. First, a small number only matters if it’s real. It’s very easy to get spurious small effects, so much so that any time you see a small effect you should wonder if it’s real. I’m ready to be forgiving here because behavioral economics is so well-replicated and common-sensically true, but I wouldn’t blame anyone who steers clear. Second, Hreha says: To be honest, you can probably use your creativity to brainstorm an idea that will get you a 3-4% minimum gain, no behavioral economics "science" required. Which leads me to the final point I'd like to make: rules and generalizations are overrated. The reason that fields like behavioral economics are so seductive is because they promise people easy, cookie-cutter solutions to complicated problems. Figuring out how to increase sales of your product is hard. You need to figure out which variables are responsible for the lackluster interest. Is the price the issue? Is the product too hard to use? Is the design tacky? Is the sales organization incompetent? Is the refund/return policy lacking? etc. Exploring these questions can take months (or years) of hard work, and there's no guarantee that you'll succeed. If, however, a behavioral economist tells you that there are nudges that will increase your sales by 10%, 20%, or 30% without much effort on your part... Whoa. That's pretty cool. It's salvation. Thus, it's no surprise that governments and companies have spent hundreds of millions of dollars on behavioral "nudge" units. Unfortunately, as we've seen, these nudges are woefully ineffective. Specific problems require specific solutions. They don't require boilerplate solutions based on general principles that someone discovered by studying a bunch of 19 year old college students. However, the social sciences have done a good job of convincing people that general principles are better solutions for problems than creative, situation-specific solutions. In my experience, creative solutions that are tailor-made for the situation at hand *always* perform better than generic solutions based on one study or another. Hreha is a professional in this field, so presumably he’s right. Still, compare to medicine. A thoughtful doctor who tailors treatment to a particular patient sounds better (and is better) than one who says “Depression? Take this one all-purpose depression treatment which is the first thing I saw when I typed ‘depression’ into UpToDate”. But you still need medical journals. Having some idea of general-purpose laws is what gives the people making creative solutions something to build upon. (also, at some point your customers might want to check your creative solution to see whether it actually gives a “3-4% minimum gain, no behavioral economics required”, and that would be at least vaguely study-shaped.) Third, everyone who said nudging had vast effects is still bad and wrong. Many of them were bad and wrong and making fortunes consulting for companies about how to implement the policies they were claiming were super-powerful. This is suspicious and we should lower our opinion of them accordingly. In a previous discussion of growth mindset, I wrote: Imagine I claimed our next-door neighbor was a billionaire oil sheik who kept thousands of boxes of gold and diamonds hidden in his basement. Later we meet the neighbor, and he is the manager of a small bookstore and has a salary 10% above the US average... Should we describe this as “we have confirmed the Wealthy Neighbor Hypothesis, though the effect size was smaller than expected”? Or as “I made up a completely crazy story, and in unrelated news there was an irrelevant deviation from literally-zero in the same space”? All the people talking about oil sheiks deserve to get asked some really uncomfortable questions. And a lot of these will be the most famous researchers - the Dan Arielys of the world - because of course the people who successfully hyped their results a lot are the ones the public knows about. Still, the neighbor seems like a neat guy, and maybe he’ll give you a job at his bookstore. V. Conclusion: Musings On The Identifiable Victim Effect I actually skipped the very beginning of Hreha’s article. I want to come back to it now. It begins: The last few years have been particularly bad for behavioral economics. A number of frequently cited findings have failed to replicate. Here are a couple of high profile examples: The Identifiable Victim Effect (featured in the workbooks I wrote with Dan Ariely and Kristen Berman in 2014)
February 20, 2023 · Original source
Gary Marcus can still figure out at least three semi-normal (ie not SolidGoldMagikarp style) situations where the most advanced language AIs make ridiculous errors that a human teenager wouldn’t make, more than half the time they’re asked the questions: 30% ACTION TRANSFORMERS: Maybe the next big thing. This is where you can give a language model an Internet connection, tell it something like "respond to all my emails" or "order some cheap Chinese food that looks good off UberEats, my credit card number is XXXXX", and it will do it. I think this technology will be ready in the next five years, although it might suffer from the self-driving car problem where you need more nines of reliability than it can provide. You want to be really sure it won't respond to an email from your boss by telling her to f@#k off, or buy a Chinese restaurant instead of food from a Chinese restaurant. I think it will start as an assistant that will run all of its decisions by you, then gradually expand out from there. AI can play arbitrary computer games at human level. I will count this as successful if an off-the-shelf AI, given a random computer game and some kind of API that lets it to against itself however many times it wants, can reach the performance of a mediocre human. The human programmers can fiddle with it to make it compatible with that particular game’s API, but this is expected to take a few days of work and not involve redesigning the AI from scratch: 25%
April 22, 2025 · Original source
6: Why did Doordash win? Now that I think about it, I haven’t heard much from GrubHub or UberEats lately. The article speculates that DoorDash started with some good strategic choices (organizing their own delivery fleet, starting in suburbs), then executed better than their competitors.
X

X is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between September 13, 2023 and July 26, 2024. The archive places it in contexts such as "This could provide X with a revenue source"; "This could provide X with a revenue source independent of advertising"; "blocked the journalist responsible (Emily Baker-White) on X". It most often appears alongside Elon Musk, Twitter, Twitter.

Article page
X
Mention count
4
Issue count
4
First seen
September 13, 2023
Last seen
July 26, 2024
September 13, 2023 · Original source
Although stories from this winter claimed that Twitter Blue was a dud, anecdotally I’ve been seeing lots more people using it lately. This could provide X with a revenue source independent of advertising and make them well-placed to survive any future chatbotpocalypse.
September 18, 2023 · Original source
>> “Although stories from this winter claimed that Twitter Blue was a dud, anecdotally I’ve been seeing lots more people using it lately. This could provide X with a revenue source independent of advertising and make them well-placed to survive any future chatbotpocalypse.”
December 04, 2023 · Original source
4: Pseudonymous accelerationist leader “Beff Jezos” was doxxed by Forbes. I disagree with Jezos on the issues, but want to reiterate that doxxing isn’t acceptable. I don’t have a great way to fight back, but in sympathy I’ve blocked the journalist responsible (Emily Baker-White) on X, will avoid linking Forbes on this blog for at least a year, and will never give an interview to any Forbes journalist - if you think of other things I can do, let me know. Apologists said my doxxing was okay because I’d revealed my real name elsewhere so I was “asking for it”; they caught Jezos by applying voice recognition software to his podcast appearances, so I hope even those people agree that the Jezos case crossed a line.
July 26, 2024 · Original source
No direct inline source block was recovered for this mention.
Xanax

Xanax is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between March 08, 2022 and September 28, 2023. The archive places it in contexts such as "benzodiazepines such as Xanax"; "replacing things like SSRIs and Xanax"; "Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien". It most often appears alongside benzodiazepines, SSRIs, 2020 election.

Article page
Xanax
Mention count
4
Issue count
4
First seen
March 08, 2022
Last seen
September 28, 2023
March 08, 2022 · Original source
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
May 18, 2022 · Original source
But recently silexan (derived from lavender) has started to stand out of the crowd. Daily Mail had an interview with psychiatry professor Hans-Peter Volz, who said that silexan should be first-line for anxiety, replacing things like SSRIs and Xanax. And a very reputable professional publication within psychiatry, The Carlat Report, published an article and a podcast touting silexan:
March 29, 2023 · Original source
The first fruit of their labor is DEA-407, which makes it hard for telemedicine doctors to prescribe controlled substances. Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien that the government has declared to be potentially addictive. The new rules say that telemedicine doctors can no longer prescribe these (or, in some cases, can prescribe them one time in an emergency).
September 28, 2023 · Original source
20: Alex Kesin makes the case for etifoxine, a French anxiety drug which is like Xanax but safer, and discusses our prospects of ever getting it in the US.
Zoom

Zoom is a recurring brand in the Astral Codex Ten archive, appearing 4 times across 4 issues between August 26, 2021 and August 08, 2024. The archive places it in contexts such as "I have heard from other classes in secondary schools where all kids attended Zoom meetings"; "there was a whole pandemic meme about people ostentatiously displaying them in their Zoom backgrounds"; "it's harder to detect psychosis over Zoom". It most often appears alongside Scott, ADHD, Congress.

Article page
Zoom
Mention count
4
Issue count
4
First seen
August 26, 2021
Last seen
August 08, 2024
August 26, 2021 · Original source
The points above argued that closing school might increase inequality (I think all the cool people are calling it “inequity” these days, but I am not that cool). But a few commenters thought that actually, Zoom school is worse than nothing on that front. For example, DasKlaus:
My mother, a teacher at a regional school in Germany (regional schools being the type of school that doesn't qualify you for university, it's grades 5-10) (in a bad neighbourhood, if it matters), has observed that [in online school] about half the students did their homework assignments and tried to keep up (or their parents made them) whereas the other half didn't really do anything at all - some of the kids don't have (enough) access to the internet, no room for themselves, siblings they had to care for while the parents used the family computer for work etc, so this is not surprising. (I have heard from other classes in secondary schools where all kids attended Zoom meetings - I expect these are socioeconomic differences).
For some kids zoom school was better than in person as far as learning. I think that was definitely the case for my 11 year old. In regular school there are lots of disruptive kids that get in the way of learning. In zoom school those kids just completely checked out, which was bad for them but actually good for my daughter because they were no longer disruptive.
July 08, 2022 · Original source
John Adams became an HBO miniseries. Hamilton became a Broadway show. The Power Broker and The Years of Lyndon Johnson became such status symbols that there was a whole pandemic meme about people ostentatiously displaying them in their Zoom backgrounds. But you never hear anyone bragging about their extensive knowledge of the Carter administration.
April 03, 2023 · Original source
I think the steelman argument against telemedicine in SOME situations is that you're restricting the physician's access to important information. For example, it seems very plausible to me that it's harder to detect psychosis over Zoom. I've taught online before and hated it because so much human nuance is lost, and I think that could be true for medicine too. That said, in many many use cases I think telemedicine is fine.
If for some reason that doesn’t work, go to a different psychiatrist and try again. You don’t have to tell them you already tried. Since everything about ADHD diagnosis and treatment is already security theater, it’s hard to say what pill mills are doing except kind of smirking under their breath while going through the rituals - as opposed to real doctors, who go through the rituals with sincere faith. Don’t get me wrong, I do think there’s a difference here. But the regulatory state isn’t set up to say “And you have to sincerely believe in the rituals or they don’t count”. So instead they punish unrelated groups, like telepsychiatrists. See also my old post Bureaucracy As Active Ingredient. The security theater doesn’t work because it’s effective. It works because it’s inconvenient enough to weed out the less motivated fakers, and some of the remaining fakers get cold feet about lying to a nice sincere psychiatrist who seems to be trying to help them. Pill mills remove the inconvenience, and seem to be nod-and-wink cooperating with liars, so the theater stops working. The only solution is to inject some inconvenience and shame back into the process somewhere, which the DEA has chosen to do by restricting telepsychiatry. They could accomplish the same goal by making you attend your appointments naked, but I guess clothing companies have better lobbyists than telepsychiatrists do. 4: Comments About Forcing Blind People To Fill Out Forms Before They Can Access Braille I analogized forcing patients to see an in-person doctor before they could access a teledoctor to forcing blind people to fill out forms before they could access Braille. Several blind people and their friends pitched in to say this was a real problem. For example, Mikolysz: Blind person here, this kind of thing is actually much more common than people imagine. Many government agencies (regardless of which particular government you mean) just assume that anybody who needs to fill a form can read and write print and/or lives with somebody who does. This is often a problem even when the form in question is specifically targeted at blind people. Non-governmental organizations, including those who specifically serve the blind, aren't much better at this either. This issue is slightly more pronounced in civil law countries, where what constitutes a legally-binding signature is clearly defined in law and you can't just Docusign your way out of the problem, but it exists everywhere, including the US. I literally had to file this kind of document today, while the main form could be filled electronically, I was required to attach a few extra documents, for GDPR and such, and those had to be printed, filled in by a sighted person, signed and scanned. The same problem exists with physical mail which you're required to read and respond to, but which is almost never available in an accessible form, a few exceptions like the American IRS notwithstanding. 5: Comments About My Caricature Of A Doctor Who Refuses To Prescribe Psych Drugs Because People Just Need Jesus Jon Cutchins writes: You don't want psychiatrists and liberals in general to be accused of an unreasoning hatred towards Christianity you should probably be more judicious in your use of anti-Christian tropes when describing everyone who is skeptical of mind-altering drugs. Mike writes: I’ve been a primary care nurse practitioner in the Bible Belt for 20yrs and not once have I even heard of a provider telling a patient they should substitute religion for psychiatric (or any) medication. It’s so easy for some people to throw around these tropes as if Christianity is some exotic, weird tribe with horrifying anthropological traits. On the other hand, fluxe writes: I am a young Christian--in my life, I have -been told by my PCP not to get an IUD because it carries "a significant risk of causing infertility or death" -had a pharmacist refuse to fill an old, male family friend's ulcer medication because it's also an abortifacient -been told by a therapist to discontinue the SSRI a different provider had prescribed and just trust in the man of the house the PCP wasn't even particularly Christian herself, but since all of her patients are she hadn't updated on IUDs since the scare back in the 70s. Our horrifying anthropological traits become everyone's problem--it might be worth listening to those who "throw around these tropes" so you can understand what they have to deal with Unfortunately I only mention this possibility because it’s happened to several of my patients. The best I can offer in terms of being unbiased and apolitical is to signal-boost posts like this one about overly woke therapists being another big problem. Alien on Earth writes: I generally like your writing and ideas, hell, I just re-uped for a year. However, in an otherwise near perfect post, you took a cheap shot at a steriotyped view of one religion thst is not popular amoungst coastal elites, that really detracts from your core point. "The worst-case is that you get one of those doctors who think that Psych Drugs Aren’t Real Because You Just Need Jesus, and then the patient has to keep looking until they find someone else." In my experience, it is the new age(y), non-religious, doctors who are least likely to like prescribing psyc. meds or who tend to give them at too low a dose or for too short a time. Certainly, I've found little correlation with their religion, if I even know it. The only correlation I've observed is that this perscription reluctance is, perhaps, slightly more common amongst middle career doctors. Perhaps it is more common in deep red areas, I don't know. However, even there, I would suggest, it is less due to religion, per se, than to "old fashion" "grit your teeth and bear it" thinking. I agree that there are many reasons people recommend against psychiatric drugs (a few are even good). Psychiatric drugs have lots of side effects and are clearly imperfect options, and I see people object to them more often when they think they have a perfect option as an alternative. Sometimes that option is Jesus. Other times it’s the trendy new somatic yoga reprocessing kundalini trauma dianetics therapy. Other times it’s LSD or ketamine or Dr. Bob’s 24-In-One Internet Nootropic. All of these work for some people, but not as much as the people pushing them think - which I guess is also true for psych drugs. I’m nervous about people who think they’ve found the answer and pressure people towards one alternative or another without presenting evidence. I’ve seen this happen enough in religious contexts that I think it was a fair thing to use as an example. 6: Comments About Which Part Of The Government Is Responsible For This Regulation ProfessorE writes: I’m not sure that what Scott wrote is even completely accurate. I have a relative who is an MD in this space, and it seems that the underlying problem is not the DEA but an actual law passed by Congress. Aren’t telemedicine regulations limited with respect to controlled substances by the Ryan Haight Act of 2008 U.S.C. § 829(e)… there may be interpretations of this act by the DEA and other agencies, but, where controlled substances are prescribed by means of the Internet, the general requirement is that the prescribing Practitioner must have conducted at least one in-person medical evaluation of the patient. It seems like a colossal overreach to ask an Executive Branch agency to overrule the plain text of the act. There are some exceptions, which Scott noted. A different way of looking at things was that the Executive Branch was highly responsive to the emergency situation of Covid. Now that it’s not an emergency, they are obligated to return to the legal framework that exists. Congress needs to change the law, not the DEA. The *data* from covid should be used as part of a cost-benefit analysis to determine whether it is reasonable to regulate telemedicine, and, if so, what regulations might address whatever problems arose. Followed by: Actually, Scott is even more off-base than I thought in my initial post. Apparently the DEA & DOJ are already proposing new changes to the 2008 Act (which seem like they violate the clear text of the act), but the act and the changes are summarized here: https://www.legitscript.com/2023/03/27/proposed-changes-ryan-haight/ Sounds like government is aware of the issue. See https://www.federalregister.gov/documents/2023/03/01/2023-04248/telemedicine-prescribing-of-controlled-substances-when-the-practitioner-and-the-patient-have-not-had For the actual changes that are being proposed. End of the day, this should be modified by Congress, not the agencies. Everyone should remember that the law was written in 2008. That’s 1 year after the very first iPhone and 2 years before the first iPad. Zoom didn’t exist (2011). None of the other technologies for video conferencing existed. Congress was attempting to fight opioid pill-mills. At the time of passage, I am willing to bet that ≈0% of patients were “Telehealth” using videoconferencing. More like phone calls and email a few times to get drugs. The law should have been amended, and it hasn’t been, but it is far from clear that it was a crazy law in the first place. I mostly accept this correction, although I’m still a bit confused - a lot of the analyses by lawyers I read said things like “Unquestionably, the DEA’s proposal is not what most industry stakeholders were anticipating. The initial reaction is the rules are more restrictive than necessary and impose concerning limitations and burdens on clinicians and the patients they treat”, and I’m confused why industry stakeholders weren’t anticipating it if the DEA had to do it in order to follow the law. And JR writes: Meanwhile, the DEA was instructed by law in -2008- to develop a special registration process for telemedicine to allow providers to prescribe controlled substances remotely. The DEA has simply failed to do so in that time, despite repeated Congressional demands to act. Don't worry, though - the DEA has said about this proposed rule that it feels this will be 'less burdensome' for providers than any kind of special registration, so it feels it has discharged its legal responsibility to create a special registration process. I am a psychiatrist having to deal with this idiocy with my patients too, and renting an office temporarily is not going to cut it. So I am going the letter route. I will probably a lose a reasonable chunk of patients I was prescribing controlled substances to. The only possible saving grace is that PCPs in this country are used to being asked to sign and complete all kinds of nonsense forms and documents so probably most of them will just do it with minimal fuss. I'm more concerned with the new requirement that all telemedicine scripts now have to be recorded by the prescriber with the date and time they were written, the PHYSICAL ADDRESS of the prescriber and patient at the time of the telehealth encounter, and have an explicit note on them that they are telemedicine prescriptions. I am less concerned about PCPs balking at writing an idiotic referral than I am skittish pharmacists refusing to fill scripts that they might interpret as being labeled equivalently to FAKE SCRIPT FOR DRUGSEEKERS Based on that comment and this, my best guess about what’s happening is: Congress passed restrictions on telemedicine in 2001, and asked the DEA to come up with a way that trusted providers could avoid those restrictions. Now that there is videoconferencing, etc, most people now believe those restrictions were too severe.
August 08, 2024 · Original source
Something that's always puzzled me a bit is girl-power pop-feminism. They've internalized a lot of Randian/Nietzschean/master-morality ideas (be strong/powerful, don't apologize for who you are, make time for yourself, don't make yourself smaller to make other people feel better, etc.). And yet their ideal doesn't look very much like Dagny Taggart. Instead of building rocket trains to Mars out of magic green metal that cures cancer or whatever, it seems like the idealized girl-boss is just leading a few Zoom meetings and then going home to do yoga and meditate on how liberated she is, and possibly writing a pop anthem about the experience. So there seems to be some kind of strange disconnect (juxtaposition?) going on there.
Anki

Anki is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 20, 2021 and September 24, 2024. The archive places it in contexts such as "experiments with Anki / Supermemo style SRS flashcards"; "medical schools (such as the spaced repetition software, Anki)"; "I have an Anki deck for all random things that I learn and don't want to forget". It most often appears alongside Ethiopia, India, Israel.

Article page
Anki
Mention count
3
Issue count
3
First seen
May 20, 2021
Last seen
September 24, 2024
May 20, 2021 · Original source
3: Best of Less Wrong: Seven Years Of Spaced Repetition Software In The Classroom. Describes a teacher’s experiments with Anki / Supermemo style SRS flashcards; the conclusion is that using them is complicated, they sort of work, but they helped him realize how much of learning isn’t about memorizing things. I appreciated this most for its theory that it’s important to make kids learn specific facts, but not so important that they remember them; teaching someone (eg) Civil War history is “training” a “predictive model” of the Civil War, war in general, and history in general which will survive and remain useful even after the specific facts and battles are long forgotten. I think this is the strongest defense of modern education, given that we do spend lots of time teaching kids things they will definitely forget. But how would you test it?
February 03, 2022 · Original source
#19: Software For Spaced Repetition And Other Education Tech With well-designed education technology, the task of understanding and memorizing vast, complicated, and important subjects, can be rendered trivial in comparison to conventional ways of learning. I'm seeking funding to create AnkiHub, software for facilitating application of evidence based learning strategies. As a software engineer who has been working closely with medical students to advance the use of ed tech in medical schools (such as the spaced repetition software, Anki) I am uniquely positioned to bring this project to success. The absence of truly effective and accessible accelerated learning tools is a bottleneck preventing millions of would be do-gooders from pursuing high impact careers like medicine and engineering. Because these careers are incredibly rigorous, they select for specific personality types, thereby weeding out those who would make incredible researchers, for example, but assume they aren't smart enough or disciplined enough. AnkiHub will empower students by democratizing accelerated learning and potentiating the ever growing wealth of quality, free, educational resources. The goal of AnkiHub is to help create a world in which anybody who wants to can become a scientist, doctor, engineer, etc, (including those in the developing world, as this technology can be compatible with cheap devices). The science of learning, memory, and performance psychology is solid; AnkiHub can fulfill the need of leveraging the insights from the literature with ease. [If you want to help, email inbox.asanchez@gmail.com]
September 24, 2024 · Original source
I have an Anki deck for all random things that I learn and don't want to forget and while reviewing yesterday there was a question about the Battle of Corinth and another about the first Roman emperor who claimed divinity.
aspirin

aspirin is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 05, 2021 and August 13, 2024. The archive places it in contexts such as "Drug 1 is aspirin"; "Like every medication, including Tylenol, aspirin, etc"; "There are lots of anti-inflammatory drugs (aspirin is one, ibuprofen is another)". It most often appears alongside COVID, FDA, SSRI.

Article page
aspirin
Mention count
3
Issue count
3
First seen
February 05, 2021
Last seen
August 13, 2024
February 05, 2021 · Original source
Drug 1 is aspirin. Drug 2 is warfarin, which causes 40,000 ER visits a year and is widely considered one of the most dangerous drugs in common use. I challenge anyone to figure out, using WebMD's side effects list alone, that warfarin is more dangerous than aspirin. I think this is because if WebMD said "aspirin is pretty safe and most people don't need to worry about it", people might use aspirin irresponsibly, die, and then their ghosts might sue WebMD. Or if WebMD said "warfarin can be dangerous, be careful with this one", people might refuse to take warfarin because "the Internet said it was dangerous", die of the stuff warfarin is supposed to treat, and then their ghosts might sue WebMD. WebMD solves this by never giving the tiniest shred of useful information to anybody.
December 22, 2021 · Original source
What are the risks? Like every medication, including Tylenol, aspirin, etc, Luvox has some common minor side effects and some rare major ones. But let’s step back a second. Fluvoxamine is a bog-standard SSRI. Its side effects are generic SSRI side effects. We give SSRIs to 30 million people a year, or about 10% of all Americans. As a psychiatrist, I’m not supposed to say flippant things like “we give SSRIs out like candy”. We do careful risk-benefit analysis and when appropriate we screen patients for various risk factors. But after we do all that stuff, we give them to 10% of Americans, compared to 12% of Americans who got candy last Halloween. So you can draw your own conclusion about how severe we think the risks are.
August 13, 2024 · Original source
Most of the relevant papers say the drugs work by preventing inflammation. This is a catch-all term for the immune response to microbes; although it helps fight the microbes, it’s slightly toxic to the rest of the body and generally bad unless you’re actively fighting an infection. In chronic inflammation, ie the thing most of us with modern diets have all the time, general bad health damages the body, the immune system mistakes the damage for a microbial infection, and it provokes a constant low-grade inflammatory response. This is bad, so (if you’re not fighting an infection) anti-inflammatories are generally pretty useful. There are lots of anti-inflammatory drugs (aspirin is one, ibuprofen is another), but inflammation is a multifaceted process and no one drug can stop it entirely.
BCS3-L1

BCS3-L1 is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between December 07, 2023 and April 16, 2024. The archive places it in contexts such as "BCS3-L1 (brand name “Lumina”) is a genetically-modified strain of the tooth decay bacterium streptococcus mutans"; "the BCS3-L1 genetically engineered bacterium"; "The rats with the new strain (BCS3-L1) got only 1/3 the normal rats’ “caries score”". It most often appears alongside Aaron, Dr. Hillman, FDA.

Article page
BCS3-L1
Mention count
3
Issue count
3
First seen
December 07, 2023
Last seen
April 16, 2024
December 07, 2023 · Original source
1: What is BCS3-L1?
BCS3-L1 (brand name “Lumina”) is a genetically-modified strain of the tooth decay bacterium streptococcus mutans.
BCS3-L1 has four main genetic modifications:
December 22, 2023 · Original source
But a parable: when you were born, your mother kissed you. Along with the kiss came a microdose of the BCS3-L1 genetically engineered bacterium. Without any teeth to cling to, it fell into the pit of your stomach and died. But she’ll kiss you again and again, transferring a few more BCS3-LI each time. In a few months, one of the colonists will find an incipient tooth and hang on for dear life. It will fight off competitors, wage epic battles that will determine the fate of the mouth for decades to come. It will win, because its genetic enhancements are pretty good. Then, if some smart people got their calculations right, it will do exactly nothing. No tooth decay. No cavities. The teeth will stay safe and clean.
April 16, 2024 · Original source
The rats with the new strain (BCS3-L1) got only 1/3 the normal rats’ “caries score”. But they didn’t get a score of zero. So maybe claims like “BCS3 represents a complete cure for cavities” are overblown. Why didn’t rats with the new strain get zero dental caries? Bacteria other than S. mutans can also cause cavities, so maybe it’s one of those. Rat trials are famous for results that don’t replicate in human trials, so take these with a grain of salt. 3: What did the latest colonization studies show? Aaron was able to retest six people who got free samples in December. Four of those people still have the bacterium. The other two don’t. Of the two failures, one had an active cavity at the time the strain was applied (which interferes with the oral microbiome), and the other had his wisdom teeth removed (which involves rinsing the mouth with strong antiseptics). Aaron hopes this shows the strain will stick around in most normal situations (though the failure in the presence of active cavities is disappointing). 4: Any new concerns about side effects? In my original post, I mentioned the possibility that this would set off Breathalyzers. Lantern was able to test this, and proved that it wasn’t a problem. Yesterday, Lao Mein suggested on Less Wrong that it might raise oral cancer risk - their post focused on people with ALDH deficiency (most common in Asians) but the calculations are too vague to be sure exactly which groups should and shouldn’t worry. This is less than 24 hours old, the company hasn’t replied yet, and is still developing. I’ll try to update people if anyone gets more clarity on this. Someone on the post mentioned that they’ve gotten worse hangovers since using the product, maybe because the constant trickle of alcohol changed the way gut flora metabolize it. 5: Any other meaningful results since the samples? Cremieux says his breath smells better. Some people have objected to this claim on the grounds that it takes ~12 months before the bacterium has colonized your mouth. One of the figures in my earlier post suggested that the bacterium might start strong, retreat for a while, and then take 12 months to fully colonize, so that might potentially explain his findings. But also, is it biologically plausible that this prevents bad breath? My impression was that bad breath came from other bacterial byproducts besides lactic acid. It might be possible in theory that the same metabolic changes that switch lactic acid to alcohol disrupt these other byproducts, but it seems kind of unlikely. An alternate explanation is that, in order to apply this product at all, you need to do a dentist-style teeth cleaning that kills your previous mouth bacteria. Maybe that improves the bad breath regardless of whether you add the Lumina afterwards? Some other people have said their mouth feels fresher or something, but realistically all of this is overwhelmingly likely to be placebo. 6: Do I “endorse” Lumina? Richard Hanania has a post about how he trusts Lumina because I’ve endorsed them. It’s extremely kind and I appreciate his respect. But also, the most I said in the original post was that I was still debating whether or not to get the treatment. My real opinion, as precisely as I can express it, is: Advance of approximately the same magnitude as fluoride: 5%
bupropion

bupropion is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 14, 2021 and August 20, 2021. The archive places it in contexts such as "bupropion (“Wellbutrin”), the fourth-most prescribed antidepressant in the US"; "Most patients will want either escitalopram or bupropion as first-line treatment"; "Advantages of bupropion: it gives you more energy and makes it easier to do things". It most often appears alongside FDA, US, COVID.

Article page
bupropion
Mention count
3
Issue count
3
First seen
April 14, 2021
Last seen
August 20, 2021
April 14, 2021 · Original source
Likewise, Próspera has 100% drug approval reciprocity. If a drug has been approved in an OECD country (eg by the FDA), it’s approved in Próspera. Again, close to my heart. Amisulpride is a great antipsychotic, probably better then most of the ones we use here. It’s approved in Europe, the UK, Australia, Israel, etc, where many studies have shown it’s safe and effective. Because none of those studies were done in the US, the FDA refuses to approve it here, and has demanded several hundred million dollars worth of more studies, which the company involved has chosen not to do (an injectable version was recently approved for nausea, but can’t be easily used for psychosis). Meanwhile, bupropion (“Wellbutrin”), the fourth-most prescribed antidepressant in the US, isn’t approved for depression in Britain; the subset of patients who respond to this medication and nothing else are out of luck. Próspera will be one of the only places in the world where patients will have access to amisulpride, bupropion, and all the other medications that one country or another is restricting because “it wasn’t invented here”.
May 25, 2021 · Original source
The short version: Depression has a combination of biological, psychological, and social causes. You can address the social causes by changing your life circumstances (and research suggests people underestimate the potential benefits of making major life changes). You can address the psychological causes with therapy; possible therapies are diverse and complicated but I especially recommend “behavioral activation” therapy (where you try to keep a schedule and also do new, interesting things) and David Burns’ book Feeling Good. You can address the biological causes with a combination of lifestyle changes, medications, and supplements. Consider exercising more and adapting a modified Mediterranean diet. Consider taking antidepressants like escitalopram and bupropion, and supplements like l-methylfolate. Other non-chemical biological options include light therapy (safe and easy), transcranial magnetic stimulation (more complicated), and electroconvulsive therapy (difficult but extremely effective last-ditch solution). If something treats your depression, continue it for some length of time depending on the type of intervention, then consider withdrawing it to see if you can maintain your mood without it.
Most patients will want either escitalopram or bupropion as first-line treatment. These medications are easy to use and have fewer side effects than most others.
Advantages of bupropion: it gives you more energy and makes it easier to do things. It sometimes makes you lose weight. Disadvantages of bupropion: it sometimes makes anxiety worse, although some studies have challenged this. It can sometimes stimulate you too much and make it hard to sleep.
August 20, 2021 · Original source
You see, Axsome thought they were in a good place, as did the stock market. Axome had a drug, bupropion-dextromethorphan, which had done well in their phase 3 trials for major depressive disorder. The next step after that is to submit the drug for approval to the FDA, which, when there are such clear indications of improvement, is usually a layup. An annoying layup, filled with lots of paperwork, but a layup.
Bupropion-dextromethorphan is an interesting case, because both bupropion and dextromethorphan alone are FDA-approved medications (bupropion as an antidepressant, DXM as a cough syrup). Then someone (maybe Axsome) did some preliminary studies suggesting that both of them together worked much better for depression than bupropion alone.
It’s actually weirder than that, because probably Axsome will have to charge really high prices for their combo drug to recoup the cost of the FDA approval process. Doctors will still have the alternative option of prescribing (very cheap) bupropion and dextromethorphan separately and telling the patient to take one of each. And yet Axsome is full of smart businesspeople who have assured their CEO that nobody will do this, and I’m sure those businesspeople are right. Why make patients take two cheap pills instead of one convenient super-expensive pill, when Yagmuk is paying the bills either way?
Codex

Codex is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 04, 2022 and January 16, 2024. The archive places it in contexts such as "using Codex to program faster"; "some people at OpenAI use Codex or other programmer-assisting-AIs"; "Imagine a programming AI like Codex that writes good code". It most often appears alongside Biological Anchors, Christiano, Codex.

Article page
Codex
Mention count
3
Issue count
3
First seen
April 04, 2022
Last seen
January 16, 2024
April 04, 2022 · Original source
Previously in series: Yudkowsky Contra Ngo On Agents, Yudkowsky Contra Cotra On Biological Anchors
For transhumanists, this debate has a kind of iconic status, like Lincoln-Douglas or the Scopes Trial. But Robin’s ideas seem a bit weird now (they also seemed a bit weird in 2008) - he thinks AIs will start out as uploaded human brains, and even wrote an amazing science-fiction-esque book of predictions about exactly how that would work. Since machine learning has progressed a lot faster than brain uploading has, this is looking less likely and probably makes his position less relevant than in 2008. The gradualist torch has passed to Paul Christiano, who wrote a 2018 post Takeoff Speeds revisiting some of Hanson’s old arguments and adding new ones.
Chess AI performance over time. Why does this matter? If there’s a slow takeoff (ie gradual exponential curve), it will become obvious that some kind of terrifying transformative AI revolution is happening, before the situation gets apocalyptic. There will be time to prepare, to test slightly-below-human AIs and see how they respond, to get governments and other stakeholders on board. We don’t have to get every single thing right ahead of time. On the other hand, because this is proceeding along the usual channels, it will be the usual variety of muddled and hard-to-control. With the exception of a few big actors like the US and Chinese government, and maybe the biggest corporations like Google, the outcome will be determined less by any one agent, and more by the usual multi-agent dynamics of political and economic competition. There will be lots of opportunities to affect things, but no real locus of control to do the affecting. If there’s a fast takeoff (ie sudden FOOM), there won’t be much warning. Conventional wisdom will still say that transformative AI is thirty years away. All the necessary pieces (ie AI alignment theory) will have to be ready ahead of time, prepared blindly without any experimental trial-and-error, to load into the AI as soon as it exists. On the plus side, a single actor (whoever has this first AI) will have complete control over the process. If this actor is smart (and presumably they’re a little smart, or they wouldn’t be the first team to invent transformative AI), they can do everything right without going through the usual government-lobbying channels. So the slower a takeoff you expect, the less you should be focusing on getting every technical detail right ahead of time, and the more you should be working on building the capacity to steer government and corporate policy to direct an incoming slew of new technologies. Yudkowsky Contra Christiano Eliezer counters that although progress may retroactively look gradual and continuous when you know what metric to graph it on, it doesn’t necessarily look that way in real life by the measures that real people care about. (one way to think of this: imagine that an AI’s effective IQ starts at 0.1 points, and triples every year, but that we can only measure this vaguely and indirectly. The year it goes from 5 to 15, you get a paper in a third-tier journal reporting that it seems to be improving on some benchmark. The year it goes from 66 to 200, you get a total transformation of everything in society. But later, once we identify the right metric, it was just the same rate of gradual progress the whole time. ) So Eliezer is much less impressed by the history of previous technologies than Paul is. He’s also skeptical of the “GDP will double in 4 years before it doubles in 1” claim, because of two contingent disagreements and two fundamental disagreements. The first contingent disagreement: government regulations make it hard to deploy imperfect things, and non-trivial to deploy things even after they’re perfect. Eliezer has non-jokingly said he thinks AI might destroy the world before the average person can buy a self-driving car. Why? Because the government has to approve self-driving cars (and can drag its feet on that), but the apocalypse can happen even without government approval. In Paul’s model, sometime long before superintelligence we should have AIs that can drive cars, and that increases GDP and contributes to a general sense that exciting things are going on. Eliezer says: fine, what if that’s true? Who cares if self-driving cars will be practical a few years before the world is destroyed? It’ll take longer than that to lobby the government to allow them on the road. The second contingent disagreement: superintelligent AIs can lie to us. Suppose you have an AI which wants to destroy humanity, whose IQ is doubling every six months. Right now it’s at IQ 200, and it suspects that it would take IQ 800 to build a human-destroying superweapon. Its best strategy is to lie low for a year. If it expects humans would turn it off if they knew how close it was to superweapons, it can pretend to be less intelligent than it really is. The period when AIs are holding back so we don’t discover their true power level looks like a period of lower-than-expected GDP growth - followed by a sudden FOOM once the AI gets its superweapon and doesn’t need to hold back. So even if Paul is conceptually right and fundamental progress proceeds along a nice smooth curve, it might not look to us like a nice smooth curve, because regulations and deceptive AIs could prevent mildly-transformative AI progress from showing up on graphs, but wouldn’t prevent the extreme kind of AI progress that leads to apocalypse. To an outside observer, it would just look like nothing much changed, nothing much changed, nothing much changed, and then suddenly, FOOM. But even aside from this, Eliezer doesn’t think Paul is conceptually right! He thinks that even on the fundamental level, AI progress is going to be discontinuous. It’s like a nuclear bomb. Either you don’t have a nuclear bomb yet, or you do have one and the world is forever transformed. There is a specific moment at which you go from “no nuke” to “nuke” without any kind of “slightly worse nuke” acting as a harbinger. He uses the example of chimps → humans. Evolution has spent hundreds of millions of years evolving brainier and brainier animals (not teleologically, of course, but in practice). For most of those hundreds of millions of years, that meant the animal could have slightly more instincts, or a better memory, or some other change that still stayed within the basic animal paradigm. At the chimp → human transition, we suddenly got tool use, language use, abstract thought, mathematics, swords, guns, nuclear bombs, spaceships, and a bunch of other stuff. The rhesus monkey → chimp transition and the chimp → human transition both involved the same ~quadrupling of neuron number, but the former was pretty boring and the latter unlocked enough new capabilities to easily conquer the world. The GPT-2 → GPT-3 transition involved centupling parameter count. Maybe we will keep centupling parameter count every few years, and most times it will be incremental improvement, and one time it will conquer the world. But even talking about centupling parameter points is giving Paul too much credit. Lots of past inventions didn’t come by quadrupling or centupling something, they came by discovering “the secret sauce”. The Wright brothers (he argues) didn’t make a plane with 4x the wingspan of the last plane that didn’t work, they invented the first plane that could fly at all. The Hiroshima bomb wasn’t some previous bomb but bigger, it was what happened after a lot of scientists spent a long time thinking about a fundamentally different paradigm of bomb-making and brought it to a point where it could work at all. The first transformative AI isn’t going to be GPT-3 with more parameters, it will be what happens after someone discovers how to make machines truly intelligent. (this is the same debate Eliezer had with Ajeya over the Biological Anchors post; have I mentioned that Ajeya and Paul are married?) Fine, Let’s Nitpick The Hell Out Of The Chimps Vs. Humans Example This is where the two of them end up, so let’s follow. Between chimps and humans, there were about seven million years of intermediate steps. These had some human capabilities, but not others. IE homo erectus probably had language, but not mathematics, and in terms of taking over the world it did make it to most of the Old World but was less dominant than moderns. But if we say evolutionary history started 500 million years ago (the Cambrian), and AI history started with the Dartmouth Conference in 1955, then the equivalent of 7 million years of evolutionary history is 1 year of AI history. In the very very unlikely and forced comparison where evolutionary history and AI history go at the same speed, there will be only about a year between chimp-level and human-level AIs. A chimp-level AI probably can’t double GDP, so this would count as a fast takeoff by Paul’s criterion. But even more than that, chimp → human feels like a discontinuity. It’s not just “animals kept getting smarter for hundreds of millions of years, and then ended up very smart indeed”. That happened for a while, and then all of sudden there was a near-instant phase transition into a totally different way of using intelligence with completely new abilities. If AI worked like this, we would have useful toys and interesting specialists for a few decades, until suddenly someone “got it right”, completed the package that was necessary for “true intelligence”, and then we would have a completely new category of thing. Paul admits this analogy is awkward for his position. He answers: Chimp evolution is not primarily selecting for making and using technology, for doing science, or for facilitating cultural accumulation. The task faced by a chimp is largely independent of the abilities that give humans such a huge fitness advantage. It’s not completely independent—the overlap is the only reason that evolution eventually produces humans—but it’s different enough that we should not be surprised if there are simple changes to chimps that would make them much better at designing technology or doing science or accumulating culture […] So I don’t think the example of evolution tells us much about whether the continuous change story applies to intelligence. This case is potentially missing the key element that drives the continuous change story—optimization for performance. Evolution changes continuously on the narrow metric it is optimizing, but can change extremely rapidly on other metrics. For human technology, features of the technology that aren’t being optimized change rapidly all the time. When humans build AI, they will be optimizing for usefulness, and so progress in usefulness is much more likely to be linear. That is, evolution wasn’t optimizing for tool use/language/intelligence, so we got an “overhang” where chimps could potentially have been very good at these, but evolution never bothered “closing the circuit” and turning those capabilities “on”. After a long time, evolution finally blundered into an area where marginal improvements in these capacities improved fitness, so evolution started improving them and it was easy. Imagine a company which, through some oversight, didn’t have a Sales department. They just sat around designing and manufacturing increasingly brilliant products, but not putting any effort into selling them. Then the CEO remembers they need a Sales department, starts one up, and the company goes from moving near zero units to moving millions of units overnight. It would look like the company had “suddenly” developed a “vast increase in capabilities”. But this is only possible when a CEO who is weirdly unconcerned about profit forgets to do obvious profit-increasing things for many years. This is Paul’s counterargument to the chimp analogy. Evolution isn’t directly concerned about various intellectual skills; it only wants them in the unusual cases where they’ll contribute to fitness on the margin. AI companies will be very concerned about various intellectual skills. If there’s a trivial change that can make their product 10x better, they’ll make it. So AI capabilities will grow in a “well-rounded” way, there won’t be any “overhangs”, and there won’t be any opportunities for a sudden overhang-solving phase transition with associated new-capability development like with chimps → humans. Eliezer answers: Chimps are nearly useless because they're not general, and doing anything on the scale of building a nuclear plant requires mastering so many different nonancestral domains that it's no wonder natural selection didn't happen to separately train any single creature across enough different domains that it had evolved to solve every kind of domain-specific problem involved in solving nuclear physics and chemistry and metallurgy and thermics in order to build the first nuclear plant in advance of any old nuclear plants existing. Humans are general enough that the same braintech selected just for chipping flint handaxes and making water-pouches and outwitting other humans, happened to be general enough that it could scale up to solving all the problems of building a nuclear plant - albeit with some added cognitive tech that didn't require new brainware, and so could happen incredibly fast relative to the generation times for evolutionarily optimized brainware. Now, since neither humans nor chimps were optimized to be "useful" (general), and humans just wandered into a sufficiently general part of the space that it cascaded up to wider generality, we should legit expect the curve of generality to look at least somewhat different if we're optimizing for that. Eg, right now people are trying to optimize for generality with AIs like Mu Zero and GPT-3. In both cases we have a weirdly shallow kind of generality. Neither is as smart or as deeply general as a chimp, but they are respectively better than chimps at a wide variety of Atari games, or a wide variety of problems that can be superposed onto generating typical human text. They are, in a sense, more general than a biological organism at a similar stage of cognitive evolution, with much less complex and architected brains, in virtue of having been trained, not just on wider datasets, but on bigger datasets using gradient-descent memorization of shallower patterns, so they can cover those wide domains while being stupider and lacking some deep aspects of architecture. It is not clear to me that we can go from observations like this, to conclude that there is a dominant mainline probability for how the future clearly ought to go and that this dominant mainline is, "Well, before you get human-level depth and generalization of general intelligence, you get something with 95% depth that covers 80% of the domains for 10% of the pragmatic impact". ...or whatever the concept is here, because this whole conversation is, on my own worldview, being conducted in a shallow way relative to the kind of analysis I did in Intelligence Explosion Microeconomics, where I was like, "here is the historical observation, here is what I think it tells us that puts a lower bound on this input-output curve". Here Eliezer sort of kind of grants Paul’s point that AIs will be optimized for generality in a way chimps aren’t, but points to his previous “Intelligence Explosion Microeconomics” essay to argue that we should expect a fast takeoff anyway. IEM has a lot of stuff in it, but one key point is that instead of using analogies to predict the course of future AI, we should open that black box and try to actually reason about how it will work, in which case we realize that recursive self-improvement common-sensically has to cause an intelligence explosion. I am sort of okay with this, but I feel like a commitment to avoiding analogies should involve not bringing up the chimp-human analogy further, which Eliezer continues to do, quite a lot. I do feel like Paul succeeded in convincing me that we shouldn’t place too much evidential weight on it. The Wimbledon Of Reference Class Tennis “Reference class tennis” is an old rationalist idiom for people throwing analogies back and forth. “AI will be slow, because it’s an economic transition like the Agricultural or Industrial Revolution, and those were slow!” “No, AI will be fast, because it’s an evolutionary step like chimps → humans, and that was fast!” “No, AI will be slow, because it’s an invention, like the computer, and computers were invented piecemeal and required decades of innovation to be useful.” “No, AI will be fast, because it’s an invention, like the nuclear bomb, and nuclear bombs went from impossible to city-killing in a single day.” “No, AI will be slow, because it will be surrounded by a shell-like metallic computer case, which makes it like a turtle, and turtles are slow.” “No, AI will be fast, because it’s dangerous and powerful, like a tiger, and tigers are fast!” And so on. Comparing things to other things is a time-tested way of speculating about them. But there are so many other things to compare to that you can get whatever result you want. This is the failure mode that the term “reference class tennis” was supposed to point to. Both participants in this debate are very smart and trying their hardest to avoid reference-class tennis, but neither entirely succeeds. Eliezer’s preferred classes are Bitcoin (“there wasn't a cryptocurrency developed a year before Bitcoin using 95% of the ideas which did 10% of the transaction volume”), nukes, humans/chimps, the Wright Brothers, AlphaGo (which really was a discontinuous improvement on previous Go engines), and AlphaFold (ditto for proteins). Paul’s preferred classes are the Agricultural and Industrial Revolutions, chess engines (which have gotten better along a gradual, well-behaved curve), all sorts of inventions like computers and ships (likewise), and world GDP. Eliezer already listed most of these in his Intelligence Explosion Microeconomics paper in 2013, and concluded that the space of possible analogies was contradictory enough that we needed to operate at a higher level. Maybe so, but when someone lobs a reference class tennis ball at you, it’s hard to resist the urge to hit it back. Recursive Self-Improvement This is where I think Eliezer most wants to take the discussion. The idea is: once AI is smarter than humans, it can do a superhuman job of developing new AI. In his Microeconomics paper, he writes about an argument he (semi-hypothetically) had with Ray Kurzweil about Moore’s Law. Kurzweil expected Moore’s Law to continue forever, even after the development of superintelligence. Eliezer objects: Suppose we were dealing with minds running a million times as fast as a human, at which rate they could do a year of internal thinking in thirty-one seconds, such that the total subjective time from the birth of Socrates to the death of Turing would pass in 20.9 hours. Do you still think the best estimate for how long it would take them to produce their next generation of computing hardware would be 1.5 orbits of the Earth around the Sun? That is: the fact that it took 1.5 years for transistor density to double isn’t a natural law. It’s pointing to a law that the amount of resources (most notably intelligence) that civilization focused on the transistor-densifying problem equalled the amount it takes to double it every 1.5 years. If some shock drastically changed available resources (by eg speeding up human minds a million times), this would change the resources involved, and the same laws would predict transistor speed doubling in some shorter amount of time (naively 0.000015 years, although realistically at that scale other inputs would dominate). So when Paul derives clean laws of economics showing that things move along slow growth curves, Eliezer asks: why do you think they would keep doing this when one of the discoveries they make along that curve might be “speeding up intelligence a million times”? (Eliezer actually thinks improvements in the quality of intelligence will dominate improvements in speed - AIs will mostly be smarter, not just faster - but speed is a useful example here and we’ll stick with it) Paul answers: Summary of my response: Before there is AI that is great at self-improvement there will be AI that is mediocre at self-improvement. Powerful AI can be used to develop better AI (amongst other things). This will lead to runaway growth. This on its own is not an argument for discontinuity: before we have AI that radically accelerates AI development, the slow takeoff argument suggests we will have AI that significantly accelerates AI development (and before that, slightly accelerates development). That is, an AI is just another, faster step in the hyperbolic growth we are currently experiencing, which corresponds to a further increase in rate but not a discontinuity (or even a discontinuity in rate). The most common argument for recursive self-improvement introducing a new discontinuity seems be: some systems “fizzle out” when they try to design a better AI, generating a few improvements before running out of steam, while others are able to autonomously generate more and more improvements. This is basically the same as the universality argument in a previous section. Eliezer: Oh, come on. That is straight-up not how simple continuous toy models of RSI work. Between a neutron multiplication factor of 0.999 and 1.001 there is a very huge gap in output behavior. Outside of toy models: Over the last 10,000 years we had humans going from mediocre at improving their mental systems to being (barely) able to throw together AI systems, but 10,000 years is the equivalent of an eyeblink in evolutionary time - outside the metaphor, this says, "A month before there is AI that is great at self-improvement, there will be AI that is mediocre at self-improvement." (Or possibly an hour before, if reality is again more extreme along the Eliezer-Hanson axis than Eliezer. But it makes little difference whether it's an hour or a month, given anything like current setups.) This is just pumping hard again on the intuition that says incremental design changes yield smooth output changes, which (the meta-level of the essay informs us wordlessly) is such a strong default that we are entitled to believe it if we can do a good job of weakening the evidence and arguments against it. And the argument is: Before there are systems great at self-improvement, there will be systems mediocre at self-improvement; implicitly: "before" implies "5 years before" not "5 days before"; implicitly: this will correspond to smooth changes in output between the two regimes even though that is not how continuous feedback loops work. I got a bit confused trying to understand the criticality metaphor here. There’s no equivalent of neutron decay, so any AI that can consistently improve its intelligence is “critical” in some sense. Imagine Elon Musk replaces his brain with a Neuralink computer which - aside from having read-write access - exactly matches his current brain in capabilities. Also he becomes immortal. He secludes himself from the world, studying AI and tinkering with his brain’s algorithms. Does he become a superintelligence? I think under the assumptions Paul and Eliezer are using, eventually maybe. After some amount of time he’ll come across a breakthrough he can use to increase his intelligence. Then, armed with that extra intelligence, he’ll be able to pursue more such breakthroughs. However intelligent the AI you’re scared of is, Musk will get there eventually. How long will it take? A good guess might be “years” - Musk starts out as an ordinary human, and ordinary humans are known to take years to make breakthroughs. Suppose it takes Musk one year to come up with a first breakthrough that raises his IQ 1 point. How long will his second breakthrough take? It might take longer, because he has picked the lowest-hanging fruit, and all the other possible breakthroughs are much harder. Or it might take shorter, because he’s slightly smarter than he was before, and maybe some extra intelligence goes a really long way in AI research. The concept of an intelligence explosion seems to assume the second effect dominates the first. This would match the observation that human researchers, who aren’t getting any smarter over time, continue making new discoveries. That suggests the range of possible discoveries at a given intelligence level is pretty vast. Some research finds that the usual pattern in science is constant rate of discovery from exponentially increasing number of researchers, suggesting strong low-hanging fruit effects, but these seem to be overwhelmed by other considerations in AI right now. I think Eliezer’s position on this subject is shaped by assumptions like: If you have an AI as intelligent as Elon Musk today, then tomorrow you can run it on more hardware with a bit of normal human algorithmic progress, and get one twice as intelligent. So even if it would take Elon years to make a breakthrough, long before those years are up you’ll have an AI that can make breakthroughs much faster.
June 20, 2023 · Original source
Last year I wrote about Open Philanthropy’s Biological Anchors, a math-heavy model of when AI might arrive. It calculated how fast the amount of compute available for AI training runs was increasing, how much compute a human-level AI might take, and estimated when we might get human level AI (originally ~2050; an update says ~2040)
The basic Bio Anchors model Compute-Centric Framework (from here on CCF) update Bio Anchors to include feedback loops: what happens when AIs start helping with AI research? In some sense, AIs already help with this. Probably some people at OpenAI use Codex or other programmer-assisting-AIs to help write their software. That means they finish their software a little faster, which makes the OpenAI product cycle a little faster. Let’s say Codex “does 1% of the work” in creating a new AI. Maybe some more advanced AI could do 2%, 5%, or 50%. And by definition, an AGI - one that can do anything humans do - could do 100%. AI works a lot faster than humans. And you can spin up millions of instances much cheaper than you can train millions of employees. What happens when this feedback loop starts kicking in? You get what futurists call a “takeoff”. The first graph shows a world with no takeoff. Past AI progress doesn’t speed up future AI progress. The field moves forward at some constant rate. The second graph shows a world with a gradual “slow” takeoff. Early AIs (eg Codex) speed up AI progress a little. Intermediate AIs (eg an AI that can help predict optimal parameter values) might speed up AI research more. Later AIs (eg autonomous near-human level AIs) could do the vast majority of AI research work, speeding it up many times. We would expect the early stages of this process to take slightly less time than we would naively expect, and the latter stages to take much less time, since AIs are doing most of the work. The third graph shows a world with a sudden “fast” takeoff. Maybe there’s some single key insight that takes AIs from “mere brute-force pattern matchers” to “true intelligence”. Whenever you get this insight, AIs go from far-below-human-level to human-level or beyond, no gradual progress necessary. Before, I mentioned one reason Davidson doesn’t like these terms - “slow takeoff” can be fast. It’s actually worse than this; in some sense, a “slow takeoff” will necessarily be faster than a “fast takeoff” - if you superimpose the red and blue graphs above, the red line will be higher at every point1. CCF departs from this terminology in favor of trying to predict a particular length of takeoff in real time units. Specifically, it asks: how long will it take to go from the kind of early-to-intermediate AI that can automate 20% of jobs, to the truly-human-level AI that can automate 100% of jobs? (“Can automate” here means “is theoretically smart enough to automate” - actual automation will depend on companies fine-tuning it for specific tasks and providing it with the necessary machinery; for example, even a very smart AI can’t do plumbing until someone connects it to a robot body to do the dirty work. CCF will talk more about these kinds of considerations later.) In order to figure this out, it needs to figure out the interplay of a lot of different factors. I’m going to focus on the three I find most interesting: How much more compute does it take to train the AI that can automate 100% of the economy, compared to the one that can automate 20%?
You get what futurists call a “takeoff”. The first graph shows a world with no takeoff. Past AI progress doesn’t speed up future AI progress. The field moves forward at some constant rate. The second graph shows a world with a gradual “slow” takeoff. Early AIs (eg Codex) speed up AI progress a little. Intermediate AIs (eg an AI that can help predict optimal parameter values) might speed up AI research more. Later AIs (eg autonomous near-human level AIs) could do the vast majority of AI research work, speeding it up many times. We would expect the early stages of this process to take slightly less time than we would naively expect, and the latter stages to take much less time, since AIs are doing most of the work. The third graph shows a world with a sudden “fast” takeoff. Maybe there’s some single key insight that takes AIs from “mere brute-force pattern matchers” to “true intelligence”. Whenever you get this insight, AIs go from far-below-human-level to human-level or beyond, no gradual progress necessary. Before, I mentioned one reason Davidson doesn’t like these terms - “slow takeoff” can be fast. It’s actually worse than this; in some sense, a “slow takeoff” will necessarily be faster than a “fast takeoff” - if you superimpose the red and blue graphs above, the red line will be higher at every point1. CCF departs from this terminology in favor of trying to predict a particular length of takeoff in real time units. Specifically, it asks: how long will it take to go from the kind of early-to-intermediate AI that can automate 20% of jobs, to the truly-human-level AI that can automate 100% of jobs? (“Can automate” here means “is theoretically smart enough to automate” - actual automation will depend on companies fine-tuning it for specific tasks and providing it with the necessary machinery; for example, even a very smart AI can’t do plumbing until someone connects it to a robot body to do the dirty work. CCF will talk more about these kinds of considerations later.) In order to figure this out, it needs to figure out the interplay of a lot of different factors. I’m going to focus on the three I find most interesting: How much more compute does it take to train the AI that can automate 100% of the economy, compared to the one that can automate 20%?
January 16, 2024 · Original source
People might make these on purpose. For example, the CIA might “encourage” big AI labs to make sleeper agents. Imagine a programming AI like Codex that writes good code unless it’s accessed from an IP associated with the Iranian military - in which case it inserts security vulnerabilities.
CVS

CVS is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between June 23, 2022 and November 28, 2023. The archive places it in contexts such as "a representative from CVS called San Francisco “the epicenter of organized retail crime"; "a representative from CVS called San Francisco “the epicenter of organized retail crime in the country”"; "Target and CVS pretend to care about shoplifting". It most often appears alongside Boston, EA, effective altruism.

Article page
CVS
Mention count
3
Issue count
3
First seen
June 23, 2022
Last seen
November 28, 2023
June 23, 2022 · Original source
Source: Ed West, do note that this example is from the UK How suspicious should we be of each type of story? There will always be an extreme right tail of overly harsh sentences, and an extreme left tail of overly lenient ones. Were the 2000s really as draconian as they felt? Is the modern era really as pathetic? Or is it all just a function of who you read and what agenda they’re pushing? Shellenberger: During California governor Jerry Brown’s time in office, voters passed several reforms aimed at reducing the size of the prison population. In 2012, voters passed a change to the Three Strikes law so that the third strike imposes a life sentence only if the new felony was serious or violent. In addition to lowering punishments for drug possession, Proposition 47, which voters passed in 2014, redefined shoplifting, forgery, petty theft, and receiving stolen property as misdemeanors when the value in question does not exceed $950. In 2016, voters approved a proposition that shortened the time it took for some nonviolent offenders to be eligible for parole and which released nonviolent offenders into drug treatment and rehabilitation. Property crimes rose in San Francisco starting in 2012. Larceny, which is shoplifting and other petty theft, rose 50 percent, from roughly 3,000 incidents per 100,000 people in 2011 to about 4,500 in 2019. Property crimes as a whole, which include larceny, motor vehicle theft, and burglary, rose from 4,000 incidents per 100,000 people in 2011 to 5,500 in 2019. One study suggests that Proposition 47 increased the rate of auto theft 17 percent and the rate of larceny (non-auto property) theft 9 percent, but discerning between causation and correlation may not be possible. Upon taking office in January 2020, [famously soft-on-crime San Francisco district attorney Chesa] Boudin followed through on his campaign promises. Instead of prosecuting and incarcerating people for breaking car windows to steal money and other items from inside, Boudin proposed creating a $1.5 million fund to reimburse car owners. But there were over 25,000 car break-ins reported in 2019. If every break-in cost just $250 in repairs, the fund would need four times that amount. And what would prevent people from falsely claiming to have been robbed in order to get city money? […] Boudin opposed efforts by the mayor and the city attorney to prevent drug dealers who had already been arrested from entering the Tenderloin. “Until the city is serious about treating addiction and the root causes of drug use and selling,” said Boudin in a statement, “these recycled, punishment-focused approaches are unlikely to succeed at doing anything more than making headlines.” Home burglaries rose in early 2021 in San Francisco. Homeowners started posting on Twitter videos from their security cameras of people breaking into homes and garages. “When I first moved here we had a car break-in problem,” said Michael Solana, a writer who works for a venture capital fund. “Now we have a home invasion problem. These things are wearing on people.” Boudin attributed the rise of burglaries in San Francisco to the decline of tourism and “people in desperate economic circumstances.” Progressive supervisor Hillary Ronen agreed. “We know that [economic insecurity and inequality] is one of the root causes of property crimes specifically,” she said. But Tom Wolf and others argued that the robberies were, like the shoplifting, done by people seeking money to buy drugs and feed their addictions. “The drugstores have been shoplifted to death and that’s all because of drug use,” said Tom. “I know. I used to do the same thing when I was out there. That’s what you do. You ‘boost.’ And then you go and you sell your stuff down at UN Plaza,” an open-air drug scene. In a May 2021 city supervisors’ meeting, a representative from CVS called San Francisco “the epicenter of organized retail crime in the country” and claimed that 85 percent of the shoplifting is committed by organized theft rings. Police broke up one such ring in October 2020 and recovered $8 million of stolen merchandise. The problem goes beyond property crime. Boudin declined to prosecute two men who went on to kill people. One man had been repeatedly arrested for stealing cars, despite having just been released from prison earlier in the year, and appeared to be abusing meth. On New Year’s Eve, 2020, the man killed two people while driving intoxicated. Police found inside of his car a semiautomatic handgun and twenty-three grams of methamphetamine. On February 4, another intoxicated driver killed a pedestrian in a stolen car. The San Francisco police had arrested him in October 2020 for possessing a stolen car, a tool for stealing cars, and what appeared to be meth. Boudin chose not to pursue charges. In December, the California Highway Patrol arrested the man again for driving a stolen vehicle under the influence. Again he was not prosecuted. The accident victim, an immigrant from Kenya, and his wife had moved to San Francisco two weeks before the fatal crash. “I blame the DA,” said the widow of the victim. The suspect, she said, “was someone who was out in the public who shouldn’t have been in the public. It was completely avoidable.” Tom said he could feel the difference on the streets. “Drug dealing is unabated and it’s not one guy, it’s fifty guys dealing fentanyl and meth,” he said. “And it’s going unabated because the district attorney says, ‘These are the nonviolent, quality-of-life crimes,’ and ‘I’m not going to prosecute them.’” [..] District Attorney Boudin was offering weaker sentences than even defense attorneys were requesting, according to Vicki Westbrook of San Francisco. “There’s a defense attorney who said, ‘It used to be that I would argue for this deal in court with the DA but now I don’t say anything because the DA is going to offer me a deal better than what I would have suggested. Somebody shot up the street with an automatic weapon. The first offer was six months in jail or time served plus two years of probation or something. And then [the DA] said, “How about thirty days in jail?”’” Vicki laughed. “You really can do anything in San Francisco,” she said. “If you do get arrested, chances are you’re going to be out of jail in less than thirty days for damn near everything except maybe killing somebody and maybe even then, too. It’s hard to say at this point.” Taking each of these points individually: Proposition 47 There are two good big studies on the effects of Prop 47, one by Public Policy Institute and one by some UCI criminologists. The PPI study finds that the proposition increased theft and car break-ins by about 10%. The UCI study finds the same, but notes that under different assumptions the effects wouldn’t quite obtain statistical significance. This seems a bit too much like post hoc trying to get rid of an inconvenient effect, plus an effect on the border of statistical significance is different from positively finding no effect. I think a reasonable interpretation is that theft and car break-ins rose about 10% because of the proposition, just as Shellenberger says. Some pro-47 sites note that most states have some limit on how much you to have to shoplift before it’s a felony, and Prop 47 brought California closer to the national average, rather than turning it into an outlier. Chesa Boudin Chesa Boudin took office two months before the COVID pandemic began. Any attempt to separate the effect of Chesa Boudin from the effect of the pandemic is doomed. Shoplifting definitely plummeted when Boudin took office, but that’s because all the stores were closed. Murders definitely rose a little after Boudin took office, but that’s because that was also when the Black Lives Matter protests happened, which demoralized police and led to a so-far-permanent spike in murders nationwide. Percent of criminals caught definitely fell when Boudin took office, but that’s because various aspects of the justice system were closed for COVID (I will grudgingly entertain speculation that a further decrease in arrest rates from 2020 to 2021 may have been a genuine Boudin effect). In the absence of any real way to judge his performance, I think San Fransicko’s points about Boudin are plausible, though speculative. Shoplifting This one is terrible. There’s a surprisingly spirited debate here (some of you may have already read Applied Divinity Studies’ article). The debate is: everyone on the ground in San Francisco - store owners, security guards, customers, random citizens - say that shoplifting has increased massively over the past decade. But statistics mostly say it hasn’t. Source here. This is shoplifting crimes per 100,000 people. Kern County is a deep red county in California (including Bakersfield) that is known for being tough on crime. Against this, seriously, everyone says that shoplifting has obviously increased. I had a patient who worked in shoplifting prevention, he told me - his psychiatrist! Who he had no reason to lie to! - that he was constantly stressed dealing with the shoplifting surge devastating the stores he covered. Here’s the San Francisco subreddit’s response to someone posting the data showing shoplifting hasn’t risen - it’s just a lot of people laughing hysterically. What’s going on? I was able to find a different set of statistics that does seem to show a longer-term increase in shoplifting (source): The very big spike at the end might be a change in reporting by one or two stores - you can find the argument here. But it does look like shoplifting went from about 125 incidents/month in the early 2010s to more like 250/month just before the pandemic. Why is this graph so different from the other one? It looks like the top one came from the Department of Justice, and the bottom one came from SFPD. I’m not sure why these report differently. When you multiply out by 800K people in SF, by 12 months/year, and 30ish days/month, the first graph corresponds to 4 shoplifting incidents per day, and the second to 6. As LouB’s analysis here points out, that seems suspiciously low for a city of 800,000 people where stores are constantly closing because of shoplifting. Maybe off by a factor of a few hundred from what we’d expect. LouB writes: The SFPD report only references shoplifting offenses that required SFPD officers to prepare an incident report. That means either the shoplifter fought security, committed additional crimes, or stole more than $950 worth of items. It’s not that SFPD’s report is erroneous, it’s just not a representative statistic. In a parallel statistic, SFPD only completes incident reports for traffic accidents when there is an injury. Therefore, thousands of noninjury accidents are handled civilly without SFPD reports the same way thousands of shoplifting offenses are handled without reports. An insurance company would not determine premium rates based solely on SFPD incident reports, nor should readers interpret SFPD shoplifting reports as anywhere near the total picture of the shoplifting epidemic in San Francisco. (this would also explain why one or two stores changing their reporting policy can produce a spike equal to everyone else in San Francisco combined) But comparing incident reports from 2010 to incident reports from 2020 should still be apples-to-apples, unless the likelihood of reporting any given incident changed in the meantime. Did it? This news article quotes a San Franciscan who says that when they try to report shoplifting incidents, the cops tell them not to because “it doesn’t make a difference”. If cops say that now more often than they used to, it would make all these statistics meaningless. (Applied Divinity Studies claims to have an argument that shows this can’t be true. It goes something like: if San Francisco was a better place to shoplift than its neighbors - eg Oakland - then shoplifters would leave Oakland to go to San Francisco, and we would see Oakland shoplifting rates falling. Oakland shoplifting rates are falling, but no more so than the rest of the state, so there can’t be increased tolerance for shoplifting in San Francisco. I find this dubious for many reasons. First of all, many of the same reasons shoplifting is up in San Francisco - like Prop 47 or soft-on-crime progressive policies - also apply to Oakland. Second, given that shoplifting fell massively everywhere because of the pandemic, it feels dubious to try to compare different cities; maybe one city had stricter pandemic lockdowns than others. Third, do criminals really shop around for friendly jurisdictions? If so, why are so many crimes like car break-ins, concentrated in “the bad part of town”? Why wouldn’t criminals leave the bad part of town for under-exploited areas with richer residents and less competition? Maybe criminals in fact aren’t very strategic or mobile? Maybe they don’t want to stand in the BART station and then take a half-hour train ride holding a bag of stolen goods?) Maybe a better argument against this being true is how stable the shoplifting rates have been over time. Wouldn’t it be weird if (let’s say) a tripling of the real shoplifting rates was matched by a third-ing of the reporting rates (rather than a halving or a quartering or whatever)? On the other hand, here’s Shellenberger with some helpful data: Some of this is probably because of Proposition 47, which made some forms of shoplifting punishable with citation rather than arrest (but wouldn’t that be a clear discontinuity rather than a gradual trend?) But overall it sure seems like shoplifting is being taken less seriously, which might encourage people to report less. Another statistic I see is that only 2.3% of shoplifting cases result in an arrest; I don’t know how this is different from the graph above with numbers in the 30s; maybe it involves different levels of what makes something a “case”. I accept that the data don’t consistently show a spike in shoplifting. But what’s the alternative? My patient who works in loss prevention in SF stores is lying to me? The nice elderly Chinese man who sold me my last pair of glasses and chatted to me about the rampant shoplifting in his mall was lying? The San Francisco police are lying? Walgreens pretends to be concerned about shoplifting as part of a dastardly plot to close a bunch of stores for no reason? Target and CVS pretend to care about shoplifting as part of a plot to restrict their stores’ opening hours for no reason? Every big store near me has suddenly gotten a security guard at the front as part of some corporate-sponsored jobs program? Maybe the conservative narrative that soft-on-crime San Francisco must be experiencing rising crime rates took on a life of its own. Maybe it infiltrated not just the usual suspects like the SF police unions, but even such supposedly-liberal bastions as the New York Times. Maybe lots of big corporations took advantage of the fake narrative to make unpopular business decisions they were planning on making anyway. And maybe ordinary San Franciscans, confronted with everyone telling them they were in a shoplifting epidemic, started paying more attention to security guards and petty criminals who had always been there, a sort of mass hallucination that gripped everyone in the city. I can’t rule this out. Americans thought crime was rising all throughout the early 2000s, when it was in fact way down. Or maybe some statistics that we already know are off by several orders of magnitude got off by an additional factor of two or so. I think this one is more likely, but I’m genuinely not sure. Other Crime From the Economist: The Center on Juvenile And Criminal Justice puts it even more starkly, arguing that “San Francisco’s ‘Crime Wave’ Is Just One Crime”: This are potentially susceptible to the same reporting bias as shoplifting. So what about homicide? Homicide is practically always reported and investigated, making it a gold standard in crime measurement. (source) Looks pretty good until 2019. I don’t expect to gain useful information post-2020; the pandemic and the post-George-Floyd murder surge will make it impossible to evaluate for local variation. What about compared to other places? For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
The very big spike at the end might be a change in reporting by one or two stores - you can find the argument here. But it does look like shoplifting went from about 125 incidents/month in the early 2010s to more like 250/month just before the pandemic. Why is this graph so different from the other one? It looks like the top one came from the Department of Justice, and the bottom one came from SFPD. I’m not sure why these report differently. When you multiply out by 800K people in SF, by 12 months/year, and 30ish days/month, the first graph corresponds to 4 shoplifting incidents per day, and the second to 6. As LouB’s analysis here points out, that seems suspiciously low for a city of 800,000 people where stores are constantly closing because of shoplifting. Maybe off by a factor of a few hundred from what we’d expect. LouB writes: The SFPD report only references shoplifting offenses that required SFPD officers to prepare an incident report. That means either the shoplifter fought security, committed additional crimes, or stole more than $950 worth of items. It’s not that SFPD’s report is erroneous, it’s just not a representative statistic. In a parallel statistic, SFPD only completes incident reports for traffic accidents when there is an injury. Therefore, thousands of noninjury accidents are handled civilly without SFPD reports the same way thousands of shoplifting offenses are handled without reports. An insurance company would not determine premium rates based solely on SFPD incident reports, nor should readers interpret SFPD shoplifting reports as anywhere near the total picture of the shoplifting epidemic in San Francisco. (this would also explain why one or two stores changing their reporting policy can produce a spike equal to everyone else in San Francisco combined) But comparing incident reports from 2010 to incident reports from 2020 should still be apples-to-apples, unless the likelihood of reporting any given incident changed in the meantime. Did it? This news article quotes a San Franciscan who says that when they try to report shoplifting incidents, the cops tell them not to because “it doesn’t make a difference”. If cops say that now more often than they used to, it would make all these statistics meaningless. (Applied Divinity Studies claims to have an argument that shows this can’t be true. It goes something like: if San Francisco was a better place to shoplift than its neighbors - eg Oakland - then shoplifters would leave Oakland to go to San Francisco, and we would see Oakland shoplifting rates falling. Oakland shoplifting rates are falling, but no more so than the rest of the state, so there can’t be increased tolerance for shoplifting in San Francisco. I find this dubious for many reasons. First of all, many of the same reasons shoplifting is up in San Francisco - like Prop 47 or soft-on-crime progressive policies - also apply to Oakland. Second, given that shoplifting fell massively everywhere because of the pandemic, it feels dubious to try to compare different cities; maybe one city had stricter pandemic lockdowns than others. Third, do criminals really shop around for friendly jurisdictions? If so, why are so many crimes like car break-ins, concentrated in “the bad part of town”? Why wouldn’t criminals leave the bad part of town for under-exploited areas with richer residents and less competition? Maybe criminals in fact aren’t very strategic or mobile? Maybe they don’t want to stand in the BART station and then take a half-hour train ride holding a bag of stolen goods?) Maybe a better argument against this being true is how stable the shoplifting rates have been over time. Wouldn’t it be weird if (let’s say) a tripling of the real shoplifting rates was matched by a third-ing of the reporting rates (rather than a halving or a quartering or whatever)? On the other hand, here’s Shellenberger with some helpful data: Some of this is probably because of Proposition 47, which made some forms of shoplifting punishable with citation rather than arrest (but wouldn’t that be a clear discontinuity rather than a gradual trend?) But overall it sure seems like shoplifting is being taken less seriously, which might encourage people to report less. Another statistic I see is that only 2.3% of shoplifting cases result in an arrest; I don’t know how this is different from the graph above with numbers in the 30s; maybe it involves different levels of what makes something a “case”. I accept that the data don’t consistently show a spike in shoplifting. But what’s the alternative? My patient who works in loss prevention in SF stores is lying to me? The nice elderly Chinese man who sold me my last pair of glasses and chatted to me about the rampant shoplifting in his mall was lying? The San Francisco police are lying? Walgreens pretends to be concerned about shoplifting as part of a dastardly plot to close a bunch of stores for no reason? Target and CVS pretend to care about shoplifting as part of a plot to restrict their stores’ opening hours for no reason? Every big store near me has suddenly gotten a security guard at the front as part of some corporate-sponsored jobs program? Maybe the conservative narrative that soft-on-crime San Francisco must be experiencing rising crime rates took on a life of its own. Maybe it infiltrated not just the usual suspects like the SF police unions, but even such supposedly-liberal bastions as the New York Times. Maybe lots of big corporations took advantage of the fake narrative to make unpopular business decisions they were planning on making anyway. And maybe ordinary San Franciscans, confronted with everyone telling them they were in a shoplifting epidemic, started paying more attention to security guards and petty criminals who had always been there, a sort of mass hallucination that gripped everyone in the city. I can’t rule this out. Americans thought crime was rising all throughout the early 2000s, when it was in fact way down. Or maybe some statistics that we already know are off by several orders of magnitude got off by an additional factor of two or so. I think this one is more likely, but I’m genuinely not sure. Other Crime From the Economist: The Center on Juvenile And Criminal Justice puts it even more starkly, arguing that “San Francisco’s ‘Crime Wave’ Is Just One Crime”: This are potentially susceptible to the same reporting bias as shoplifting. So what about homicide? Homicide is practically always reported and investigated, making it a gold standard in crime measurement. (source) Looks pretty good until 2019. I don’t expect to gain useful information post-2020; the pandemic and the post-George-Floyd murder surge will make it impossible to evaluate for local variation. What about compared to other places? For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
May 26, 2023 · Original source
No direct inline source block was recovered for this mention.
November 28, 2023 · Original source
No direct inline source block was recovered for this mention.
DoorDash

DoorDash is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 26, 2021 and January 13, 2026. The archive places it in contexts such as "It's just a link to their UberEats/DoorDash pages"; "Why did Doordash win? Now that I think about it, I haven’t heard much from GrubHub or UberEats lately"; "You want to join our Doordash?". It most often appears alongside Altman, Bay Area, Cremieux.

Article page
DoorDash
Mention count
3
Issue count
3
First seen
February 26, 2021
Last seen
January 13, 2026
February 26, 2021 · Original source
Their restaurant is attached to a store that sells some of their plant-based meat in packaged form for people who want to cook with it at home. I haven’t explored this place as much as I want because getting delivery is complicated - they seem to use DoorDash kind of inconsistently.
Their website has ten different accessibility options, including "pause animations" and "dyslexia friendly", hidden in an unobtrusive corner menu. This is great. It seems to be courtesy of a site called UserWay, so check them out if you like user-readable websites. This is the most accessible site I have ever seen, which makes it ironic that it has no actual content. It's just a link to their UberEats/DoorDash pages, all of which are inaccessible as usual.
If you’ve never had an Impossible Burger, start there. I like Umami Burger, but most restaurants can pull this off fine. You can even get one at your local Burger King.
April 22, 2025 · Original source
6: Why did Doordash win? Now that I think about it, I haven’t heard much from GrubHub or UberEats lately. The article speculates that DoorDash started with some good strategic choices (organizing their own delivery fleet, starting in suburbs), then executed better than their competitors.
January 13, 2026 · Original source
There is no food, but Sam and Tran are hunched over a laptop. “You want to join our Doordash?” asks Tran.
Sam types in spaghetti bolognese, delicious, scrumptious, meaty, trending on DoorDash, --dangerously-skip-parmesan and hands it back to Tran, who clicks ORDER.
eBay

eBay is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 19, 2023 and January 25, 2024. The archive places it in contexts such as "Amazon and eBay have made it trivial to exchange money"; "what if there was an Amazon or an eBay for paying politicians not to run?"; "eBay’s policy of promoting inclusiveness by displaying shirts on ethnically diverse models". It most often appears alongside Amazon, Trump, 1979 study on capital punishment by psychologists.

Article page
eBay
Mention count
3
Issue count
3
First seen
April 19, 2023
Last seen
January 25, 2024
April 19, 2023 · Original source
Also, what was up with stamp and coin collectors? This seems like a different phenomenon: surely nobody wanted to identify with the US Postal Service. I have a better hypothesis for why this pastime has died out: collectors enjoyed the thrill of hunting for a rare piece, but Amazon and eBay have made it trivial to exchange money for whatever coins/stamps you want. I’m not sure this works; when I was young in the 90s, there was a store in my hometown that sold rare coins; even then I could have gone to the store and walked out with a pretty good collection. But maybe the fact that I would need multiple books to know which coins were “rare”, and that the store could have been out of one or two valuable pieces, was enough cover to make it still seem interesting and impressive. Now there’s no sense that you have to really care about stamps or coins to have a great stamp/coin collection: you just need a higher budget than whoever else typed “stamps and coins” into the eBay search function.
December 12, 2023 · Original source
“Have you read Going Infinite? The book on Sam Bankman-Fried? Not that I generally approve of Sam Bankman-Fried. It’s just that - the book says Sam tried to bribe Trump not to run in 2024. Apparently Trump was willing to do it for $5 billion. And again, not to say Sam Bankman-Fried was right or anything, but obviously if you have $5 billion and you’re a Democrat, then that’s the best use of your money, right? And not to say that I wish he was never caught and had gone on to become a multi-deca-billionaire, but, well, you know . . . “ he trailed off. “Anyway, I was reading about all these delicate negotiations between Sam’s people and the Trump team, and it was funny - here’s this guy who’s famous for creating markets, and he’s stuck with boring old Mk 1.0 backchannel negotiations. So I thought - what if there was an Amazon or an eBay for paying politicians not to run? We wouldn’t have to get Trump our first year. We could start with your local city council member - Aaron Peskin, someone like that. Lots of people would pay Aaron Peskin money not to run. Then we build up from there.”
January 25, 2024 · Original source
A Google search brought up this lovely t-shirt. I think eBay’s policy of promoting inclusiveness by displaying shirts on ethnically diverse models may have failed them in this case. This is only the tip of the iceberg. Donald Trump Jr has a book called Triggered, and a biweekly TV show of the same name. Sheila Jeffreys’ biography is called Trigger Warning: My Radical Feminist Life. Jeffreys and Trump Jr may not have much else in common, but they are united by a shared appreciation for applying this technical psychiatric term to politics. I think this makes the most sense if political triggering and psychiatric triggering are literally the same thing because political toxicity is a subspecies of PTSD. D2: Persistent and exaggerated negative beliefs or expectations about oneself, others, or the world. Do I even need to explain this one? D3: Persistent distorted cognitions about the cause or consequences of the traumatic events that lead the individual to blame himself or others. As stated, this doesn’t really apply to politics. But I claim this is an overly restrictive description of the true problem, which is a general distortion of cognition around traumatic stimuli. See for example Reasoning, trauma, and PTSD: insights into emotion–cognition interaction. Here the researchers make people solve math/logic puzzles with five apples and eight oranges or whatever; as usual, most people do fine. Then they change the content to traumatic stimuli, like five rapists and eight abusers. Nobody is particularly happy about this change, but traumatized people seem to do worse when the stimuli relate to their own trauma. This is an exact analog to the “five Democrats and eight assault weapons” task discussed above; I don’t know if one line of research inspired the others, but they show some similar results. Other people have even more general findings. You may remember the Stroop Effect, where people have to say the color of words without getting distracted by their content. One variant is the Emotional Stroop Effect, where instead of giving color words (“yellow”, “red”, etc), you use emotional words and traumatic stimuli. Traumatized people tend to do worse at Emotional Stroop tasks relating to their specific trauma. See Modification of cognitive biases related to posttraumatic stress: A systematic review and research agenda. See also The Precision Of Sensory Evidence for a discussion of how this effect might happen. E1: Irritable behavior and angry outbursts (with little or no provocation) typically expressed as verbal or physical aggression toward people and objects. As seen at your family Thanksgiving table. Politics makes otherwise kind people into angry jerks. E3: Hypervigilance This is defined as a heightened awareness of surroundings, constantly scanning for danger, and misinterpreting innocuous stimuli as threatening. Wikipedia describes it as “there is a perpetual scanning of the environment to search for sights, sounds, people, behaviors, smells, or anything else that is reminiscent of activity, threat or trauma”. Dog whistles. Microaggressions. The hallmark of the advanced political partisan is the ability to describe everything the other side (or neutral third parties) do as secretly a political offense, and to reduce every possible situation to their issue of choice. For the past ten years, I’ve been involved in the anti-AI-existential risk movement, and have gotten to know other people in this movement pretty well. I can say with high certainty that the number one motive of these people is that they do not want to be killed by robots. Still, over the years people have ascribed every possible motive to us except that one, for example: It’s a plot by Big Tech to distract from other harms they are committing.
fluoxetine

fluoxetine is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 22, 2021 and March 08, 2022. The archive places it in contexts such as "they think everything accumulates as slowly as fluoxetine does"; "16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac)"; "30 mg fluoxetine equivalent". It most often appears alongside FDA, SSRIs, serotonin.

Article page
fluoxetine
Mention count
3
Issue count
3
First seen
February 22, 2021
Last seen
March 08, 2022
February 22, 2021 · Original source
A recent study, Antidepressant drugs act by directly binding to TrkB neurotrophin receptors (h/t Derek Lowe) proposes a dramatic solution. The authors, mostly based out of a well-known lab in Helsinki, argue that antidepressants bind to TrkB directly, modifying it so that it responds more vigorously to BDNF. They explored the TrkB receptor in more detail than anyone had before, discovering some new functions (it binds to cholesterol) and a new binding site. They found that three antidepressants - fluoxetine ("Prozac"), imipramine, and ketamine, all bind to the new site (the textbooks say all three of these work in different ways). Three control non-antidepressant chemicals - diphenhydramine ("Benadryl"), chlorpromazine ("Thorazine"), and isoproterenol don't. Once bound, the antidepressants seem to help TrkB receptors get to the parts of the cell where they can be useful. Then they show antidepressants don't work on mice with a mutation that breaks TrkB's ability to bind antidepressants (but not its ability to bind BDNF). In other words, the antidepressant effect was coming from direct antidepressant-TrkB binding, not serotonin -> BDNF -> TrkB binding! The serotonin doesn’t matter at all!
The TrkB paper cites two papers saying antidepressants still work on mice genetically engineered so they can't reuptake serotonin, which would mean serotonin isn't involved in their effects and it's probably this new TrkB thing. They also cite one paper saying the antidepressants don't work on the mice, just as the standard theory would predict. They imply this means it's two to one, but reviews of this literature make it sound like the antidepressants not working is the more common finding, and when I Google around on this subject most papers seem to agree. @zenbrainest @Dereklowe (excuse my self-promotion) We did show that SERT M172 mice lost acute and chronic SSRI behavioral and neurogenic efficacy, which should retain all TrkB effects. Thus TrkB effects are insufficient alone to produce AD effects. ","username":"anackenoff","name":"Alex Nackenoff, Ph.D.","profile_image_url":"","date":"Fri Feb 19 17:18:54 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":3,"like_count":15,"impression_count":0,"expanded_url":{"url":"https://pubmed.ncbi.nlm.nih.gov/26514584/","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/39b37056-9b5e-4056-9952-3d45751866ec_1200x1200.png","title":"Essential Contributions of Serotonin Transporter Inhibition to the Acute and Chronic Actions of Fluoxetine and Citalopram in the SERT Met172 Mouse - PubMed","description":"Depression is a common mental illness and a leading cause of disability. The most widely prescribed antidepressant medications are serotonin (5-HT) selective reuptake inhibitors (SSRIs). Although there is much support for 5-HT transporter (SERT) antagonism as a basis of antidepressant efficacy, this…","domain":"pubmed.ncbi.nlm.nih.gov"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> Likewise, there are a lot of papers showing that antidepressant treatment increases levels of BDNF and that this seems to be necessary for its effects. If antidepressants just positive-allosteric-modulated TrkB, we'd expect to see the same amount of (maybe less) BDNF.
Anyway, I promised I'd get back to the idea of antidepressants eventually accumulating over months until they reach the level where they can affect TrkB. I have been reading stuff about antidepressants for years and never heard anything about them accumulating like this? I mean, they accumulate over five or six days as you wait for them to reach plasma steady state, but that's very different from the month or two it takes to work. Fluoxetine does accumulate for a month or two, just because of its half-life, but since other SSRIs aren't like that, it's probably not responsible for class-wide features.
March 31, 2021 · Original source
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
They find antidepressants are most effective (the first graph, marked "response") at doses equivalent to 30 mg of fluoxetine (aka Prozac; 1 fluoxetine-equivalent = 5 of the imipramine-equivalents the other study uses). If that were true, the most effective dose of every SSRI would be:
Overall, I think there we're on shaky ground saying that any antidepressant works better at high doses than low-to-medium ones of about 30 mg fluoxetine equivalent. But despite what the FDA says, prescribing high doses of Lexapro probably isn't any worse than prescribing high doses of any other antidepressant, and it might even be better. In the rare cases where I think it might help, I plan to continue prescribing doses of up to 30 mg without worrying at all, and up to 40 mg while worrying only slightly.
March 08, 2022 · Original source
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator! (or maybe that’s just an urban legend, I’ve never found proof either way) The discovery of endorphins (ie endogenous opiates) helped shed light on the brain’s reward system. So the discovery of a sort of endogenous benzodiazepine was pretty exciting. Maybe it’s some kind of master control switch for anxiety or something? Psychiatrists only know two ways to respond to an exciting new thing: publishing breathless studies claiming that it’s the true mechanism of action for SSRIs, and publishing breathless studies claiming that it’s the true biological basis of depression. This time, they did both: see eg Fluoxetine elevates allopregnanolone levels in female rat brain and The role of allopregnanolone in depressive-like behaviors. The basic theory was that stress / social isolation / etc → decreased allopregnanolone → something something BDNF and synaptogenesis → depression. And SSRIs → increased allopregnanolone → something something BDNF and synpatogenesis → recovery! Change the word “allopregnanolone”, and that’s every theory in psychiatry. But this particular theory had two extra pieces of evidence: premenstrual dysphoric disorder and postpartum depression. Remember, allopregananolone is a natural metabolite of the female hormone progesterone. Progesterone levels go up during pregnancy and the ~18th day of the menstrual cycle, then crash back down after delivery and the ~24th day of the menstrual cycle. Meanwhile, some women get depressed after delivering a baby, or on the ~24th day of their menstrual cycle. Suspicious! Maybe it’s because their progesterone was getting converted into allopregnanolone, an antidepressant hormone that affects mood! (why doesn’t every woman get PPD and PMDD? This study suggests that women with PMDD have altered sensitivity to allopregnanolone; plausibly people with PPD have some other form of altered sensitivity. In case you have the same question I do: the correlation between PMDD and PPD is not 100% but still pretty significant) History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
GPT-5

GPT-5 is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between July 17, 2023 and November 20, 2025. The archive places it in contexts such as "then a bunch with GPT-5"; "a forecasting AI built off GPT-5 or 6 might get only small improvements"; "I have trouble not saying “please” and “thank you” to GPT-5 when it answers my questions". It most often appears alongside OpenAI, GPT-4, AI consciousness.

Article page
GPT-5
Mention count
3
Issue count
3
First seen
July 17, 2023
Last seen
November 20, 2025
July 17, 2023 · Original source
One good thing about order-following AI is that it’s useful now, when AIs aren’t agentic enough to have real goals and we just want to use them as tools in commercial applications. The hope is that we do this a bunch with GPT-4, then a bunch with GPT-5, and so on, and by the time we have a real superintelligence, we’ve worked out some of the kinks. I’m not sure how Musk’s maximally-curious AI helps do office work, which means there’s going to be more of a disconnect between current easily-tested applications and the eventual superintelligence that we need to get right.
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
November 20, 2025 · Original source
I never had a Tamagotchi, but I had stuffed animals as a kid. I’ve outgrown them, but I haven’t thrown them out - it would feel like a betrayal. Offer me $1000 to tear them apart limb by limb in some horrible-looking way, and I wouldn’t do it. Relatedly, I have trouble not saying “please” and “thank you” to GPT-5 when it answers my questions.
The argument against: AI companies have an incentive to make AIs that seem conscious and humanlike, insofar as people will feel more comfortable interacting with them. But they have an opposite incentive to make AIs that don’t seem too conscious and humanlike, lest customers start feeling uncomfortable (I just want to generate slop, not navigate social interaction with someone who has their own hopes and dreams and might be secretly judging my prompts). So if a product seems too conscious, the companies will step back and re-engineer it until it doesn’t. This has already happened: in its quest for user engagement, OpenAI made GPT-4o unusually personable; when thousands of people started going psychotic and calling it their boyfriend, the company replaced it with the more clinical GPT-5. In practice it hasn’t been too hard to find a sweet spot between “so mechanical that customers don’t like it” and “so human that customers try to date it”. They’ll continue to aim at this sweet spot, and continue to mostly succeed in hitting it.
(wait, what is a GPT “instance” in this context, anyway? Do we think of “the weights” as a conscious being, such that there is only one GPT-5? Do we think of each cluster of GPUs as a conscious being, such that the exact configuration of the cloud has immense moral significance? Again, I predict we ignore all of these questions in favor of whether the AI you are looking at has a simulated face right now.)
imipramine

imipramine is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between March 31, 2021 and December 22, 2021. The archive places it in contexts such as "maximum doses of those medications are 60 mg and 80 mg ... convert these to mg imipramine equivalents"; "imipramine, nortriptyline, and clomipramine are all reasonable choices"; "100 mg imipramine-equivalent dose". It most often appears alongside FDA, escitalopram, SSRI.

Article page
imipramine
Mention count
3
Issue count
3
First seen
March 31, 2021
Last seen
December 22, 2021
March 31, 2021 · Original source
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
They find antidepressants are most effective (the first graph, marked "response") at doses equivalent to 30 mg of fluoxetine (aka Prozac; 1 fluoxetine-equivalent = 5 of the imipramine-equivalents the other study uses). If that were true, the most effective dose of every SSRI would be:
May 25, 2021 · Original source
Amitriptyline is my preferred tricyclic, a large and sprawling class of older antidepressants. Other people might have different preferred tricyclics; imipramine, nortriptyline, and clomipramine are all reasonable choices in different situations. It can also cause tiredness and weight gain, and has a small risk of heart problems in vulnerable/older people. On the other hand, in Andrea Cipriani’s massive meta-analysis of antidepressant efficacy, it ranked first out of 21 different drugs (my third- tier suggestions weren’t studied, because the researchers were cowards).
December 22, 2021 · Original source
For some reason the same experts who don’t mind prescribing SSRIs when people have mild depression freak out about prescribing them when they’re the only evidence-based oral medication for a deadly global pandemic. “What about SSRI withdrawal?”, they ask. After a ten day course? On 100 mg imipramine-equivalent dose? Minimal. “What about long QT syndrome?” The VA system took 35,000 high-risk older patients off of an unusually-likely-to-cause-QT-syndrome SSRI in 2011, and were unable to find any evidence that this prevented even a single case of the syndrome, let alone any negative outcome!
Impossible Burger

Impossible Burger is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 26, 2021 and May 30, 2024. The archive places it in contexts such as "If you’ve never had an Impossible Burger, start there"; "delicious Swedish meatballs made with Impossible Burger"; "Swedish meatballs made with Impossible Burger". It most often appears alongside Alcoholics Anonymous, Bay Area, EA.

Article page
Impossible Burger
Mention count
3
Issue count
3
First seen
February 26, 2021
Last seen
May 30, 2024
February 26, 2021 · Original source
By this point you’ve probably tried Impossible Burgers, and you know that restaurants can do some pretty impressive things with them. But there are so many interesting meat dishes - what if you want something other than a burger? This market is still developing, but I live in the Bay Area, which is probably its epicenter. And I’m mostly-vegetarian, so I have no choice but to try it out.
If you’ve never had an Impossible Burger, start there. I like Umami Burger, but most restaurants can pull this off fine. You can even get one at your local Burger King.
If you’ve had Impossible Burgers and are looking for something more interesting, my favorite dish from this round of reviews was the chicken at Nature Vegetarian Restaurant. General Tao’s and Salt & Pepper were especially good.
November 30, 2023 · Original source
And I’m a terrible vegetarian. If there’s meat in front of me, I’ll eat it. Luckily I’ve cultivated an EA friend group full of vegetarians and pescetarians, and they usually don’t place meat in front of me. My friends will cook me delicious Swedish meatballs made with Impossible Burger, or tell me where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast). And the Good Food Institute (an EA-supported charity) helps ensure I get ever tastier fake meat every year.
May 30, 2024 · Original source
And I’m a terrible vegetarian. If there’s meat in front of me, I’ll eat it. Luckily I’ve cultivated an EA friend group full of vegetarians and pescetarians, and they usually don’t place meat in front of me. My friends will cook me delicious Swedish meatballs made with Impossible Burger, or tell me where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast). And the Good Food Institute (an EA-supported charity) helps ensure I get ever tastier fake meat every year.
Instagram

Instagram is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 06, 2022 and May 15, 2025. The archive places it in contexts such as "more social media (Instagram, Reddit)"; "Instagram “find yourself” therapy culture"; "What about the age of TikTok and Instagram?". It most often appears alongside Twitter, US, YouTube.

Article page
Instagram
Mention count
3
Issue count
3
First seen
April 06, 2022
Last seen
May 15, 2025
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
August 08, 2024 · Original source
If Nietzsche is really saying “ignore the strictures of society; pursue the destiny written upon your own soul”, how does that differ from Instagram “find yourself” therapy culture? Other than that Nietzsche expects your soul to say “conquer Europe” and Instagram expects it to say “ditch your boyfriend and date a yoga instructor”?
May 15, 2025 · Original source
Wise words - in 2011, when SRTHMK was written. What about the age of TikTok and Instagram?
Suppose that screens genuinely harm many students. Does that mean that parents should keep screens away from toddlers? It depends on the mechanism of harm. If phones harm kids by gradually damaging their brains somehow (chronic dopamine poisoning? I’m pretty sure this isn’t a real thing, but I’m sure some self-help guru has an infomercial that disagrees), and this damage is worst during childhood, then sure, keep your kids away. But if phones are merely very addictive - so addictive that college students scroll through social media instead of going to class - then it’s less obvious that it matters. You can’t realistically prevent your teenager from using a phone during college; if she has addictive tendencies, she’s going to get addicted. So why not save yourself some babysitting time when she’s three years old by letting her go on Toddler Instagram?
My daughter would absolutely dominate Toddler Instagram. RIP to all the other Toddler Instagram influencers. Or does giving kids phones at age three (when they have no hope of resisting) deny them the right to exercise their free will at age eighteen (when they might have some slight hope)? Do Caplan’s exhortations to remember the behavioral genetics literature apply here? Will those with phone addiction genes get addicted no matter how we raise them? Only 10% of variability in alcohol addiction is shared environmental (eg potentially due to parenting); should this also be our estimate for phone addiction?
Minecraft

Minecraft is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between January 12, 2022 and January 13, 2026. The archive places it in contexts such as "switched our dates to a Minecraft virtual world"; "let's say it's Minecraft, because why not—and it's just such a positive experience for you"; "I started a data center company in Minecraft". It most often appears alongside Sam, 286, 8088.

Article page
Minecraft
Mention count
3
Issue count
3
First seen
January 12, 2022
Last seen
January 13, 2026
January 12, 2022 · Original source
Then COVID hit. We switched our dates to a Minecraft virtual world, where we built a house together. At the time, I completely missed the kabbalistic significance of this.
April 27, 2023 · Original source
…where Sam fills in the northwest and southeast squares, then claims a correlation, draws a line, and points to high-status/deep-engagement as a single unified concept. But the southwest square could be “writes a wacky Shakespeare fanfiction, Romeo & Juliet II, in blank verse and period-appropriate language”, and the northeast square could be “publishes a dissertation on some irrelevant aspect of word frequency changes across English plays to prove something about linguistics”. And then having conflated these two things, he goes on to conflate a third thing, Shakespeare vs. Marvel. I’m not up to date on what goes on in academic literature departments, but Freddie de Boer says they’re increasingly offering “Spiderman Studies” classes in attempts to stay culturally relevant; probably Spiderman professors engage with Spiderman on the same deep level that Shakespeare professors engage with Shakespeare. If we made this a cube - high-status vs. low-status forms of engagement along one axis, Shakespeare vs. Spiderman along another axis, and deep vs. shallow engagement along the third - would anything be left of the “nerd” cluster as Sam describes it? I’m not sure. 2. Comments With Strong Opinions On The Definition Of Nerds, Geeks, Etc There were many of these. One common theme was that in the 70s, “nerd” was almost synonymous with “person who is only into unpopular things”, for example sci-fi, comics, and RPGs, all of which were unpopular in the 70s. Then those things became very popular, but the people who were interested in them still get called “nerds”. So now people like Kriss use “nerd” almost synonymously with “person who is only into popular things”. So we have a word which denotes either interest in unpopular things or interest in popular things, depending on who’s using it and when they last updated their lexicon. In the 70s, it was more reasonable to group “interested in math and computers” and “interested in sci-fi and RPGs” together, because both were unpopular and tended to involve the same group of socially maladept young men. Now math is still hard and unpopular; computers are hard in the sense that it’s tough to learn programming languages, but universally used and beloved; sci-fi and RPGs are very popular, and the typical sci-fi fan is closer to a socially-adept albeit “quirky” young woman. If words are hidden inferences, the inference represented by “nerd” - that sci-fi fandom, interest in math, interest in computers, maleness, poor social skills, and nonconformity with mainstream interests all go together - is now thoroughly false, dooming us to conversations like this one. Attempts to repurpose the several different words used to refer to the math/sci-fi/awkward/unpopular cluster to represent different aspects of its successor clusters have mostly failed. Sample comments from this section: Coagulopath writes: To me, being a nerd requires a degree of swimming against the cultural tide. It's weird and unpopular to be into trains, so the fact that you are indicates you have a bit of character (or are socially oblivious, which is also kind of endearing). The problem (and I think Kriss alludes to this) is that nerd stuff went mainstream in the past few decades. Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films. There's no longer any sense that nerds are the underdog. But what does it say about you when you wear a Star Wars shirt? You're pledging allegiance to the biggest, most popular club imaginable. Is that a brave stance? Those people always make me think "if you lived in the SW universe, you'd be on the side of the Empire". In general, I am creeped out by effusive public adoration for things that are near-universally loved. Like The Beatles. Or bacon. Or dogs. Or science (Neil DeGrasse Tyson's whole shtick). Regardless of how I feel about those things on the object level, there's no glory in joining a culture war when you're signing on to the winning side. Tolaughoftenandmuch writes: All this is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, Ghatanathoah writes: I also wouldn't say that nerd stuff only went mainstream in the last decade, it's not like the first 3 Star Wars movies were obscure arthouse pictures. I think the reason Marvel took off is just innovations in storytelling: movie producers finally figured out a way to adapt the gloriously arcane and convoluted lore of superhero comics in a way that could appeal to mainstream audiences in addition to nerds (much how George Lucas figured out how to get mainstream audiences to love the space operas nerds had been enjoying for decades before 1977). And Melvin writes: Comic book movies had always been pretty popular. Superman was the top grossing movie of 1979 despite coming out in 1978. Superman 2 was the second top grossing movie of 1981. Batman was the second top grossing movie of 1989. Batman Returns was the top grossing movie of 1992. Batman Forever was the top grossing movie of 1995. Spider-man was the third top grossing movie of 2002 (behind Lord of the Rings and Harry Potter movies). That's about all I can be bothered looking up right now but you get the idea, superhero movies have been popular since the 1970s. Kaitian writes: I think being a nerd requires being a bit socially clumsy about your interest, and talking or signalling about it in situations where most people don't expect it. So being a nerd about completely mainstream stuff like pop music or football is not possible, that's just fandom. Being a nerd about very well known and relatively well-respected stuff like classical music or birdwatching is rare, because most people who are classy enough to care about the thing in the first place are also classy enough to know when to shut up about it. But comics? Star trek? Power metal? They have fairly low barriers to entry *and* most people don't care about them, so there's plenty of opportunities to bring it up to people who don't want to hear about it. So that's why I think nerdery usually attaches itself to the typical targets. J.R. Leonard has as good a terminology proposal as anyone: I think what's missing is that Kriss uses "nerds" as his foil, but what he's talking about would better be described as fan culture. Deiseach teaches us the etymology of “geek”. The very distant etymology is from German gek, a relative of “cackle” → geck, a fool/madman (who was presumably cackling all the time). But this comes down to us through the early American institution of the geek show. From Wikipedia (cw: disturbing): Geek shows were an act in traveling carnivals and circuses of early America and were often part of a larger sideshow. The billed performer's act consisted of a single geek, who stood in the center ring to chase live chickens. It ended with the performer biting the chickens' heads off and swallowing them. The geek shows were often used as openers for what are commonly known as freak shows. It was a matter of pride among circus and carnival professionals not to have traveled with a troupe that included geeks. Geeks were often alcoholics or drug addicts, and paid with liquor – especially during Prohibition – or with narcotics. More obvious but I went surprisingly long without realizing it: “fan” (as in “sports fan”) is just short for fanatic. 3. Comments About Collecting The veteran collectors in the comments said that my theory (the Internet makes collecting too easy) was only a small part of the decline. The bigger part is that most coin collecting begins with the wonder of finding a rare coin in your change, and most stamp collecting begins with the wonder of finding a rare stamp on your mail, and the rise of credit cards and emails means people aren’t handling coins and stamps as much in their daily lives. Tom Metcalf writes: I'd guess many coin collectors got their start being patient enough to sort through change to see if they had e.g. a wheat cent or silver dime, but first of all, who pays with cash and gets change, and the chances of finding something collectible are orders of magnitude smaller than, say, the '90s. And stamp collectors would have started saving the stamps on mail sent to their house, but how frequently do you get stamped mail anymore? My 79-year old father goes to stamp shows, because one of his hobbies is to buy sheets of old but common unused stamps for less than face value. They are still valid postage, and then he uses them to personalize the stamps he puts on letters he sends to various people. And most of the other people at stamp shows are about his age. He does have some stamps he thinks are interesting that he's held onto, but the dealers at the stamp shows think they're common and uninteresting. So there's a decreasing number of stamps that might be "worth something" and a net loss of collectors in the hobby, and then every time a collector dies and his heirs have no interest in his collection and that many more stamps make their way to dealers who now have one less buyer. Too bad "sending paper letters with vintage but still valid stamps" never caught on with the hipsters. Art writes: The widespread adoption of email created a world where a letter is almost certainly junk mail or a bill. Nobody looks forward to hearing from a good friend from across the country now when picking up the day’s mail. If letters are not interesting why would stamps? The same for coins. Nobody uses cash, and getting a pile of coins with no significant value (inflation) is just an annoyance. These objects have passed into irrelevance. Still, it seems like some little pieces of joy and wonder have passed from our lives. Nathan Savir writes: I collect coins and I think the description of the hobby (and its putative death) isn't quite right. 1. Rare coins are in fact hard to find, even in today's internet world. They are usually sold in auctions, which might happen online, but still not that frequently. It's not unusual for examples some specific rare coin to be sold only once every few years. If the coin is also obscure, it may not be prohibitively expensive, so this kind of situation isn't the sole province of rich people. 2. One area of collecting is to get all the rare items. Another is to get all the minor varieties of a common item. These varieties may not be very rare, but it still takes a lot of effort to be able to distinguish them and to find them. Some collectors will obtain large numbers of relatively common coins and sort through and scrutinize them to try to identify interesting varieties. 3. An important part of collecting is getting good deals. This is surely a lot harder than it used to be because sellers can more easily figure out what things are worth and you won't find something grossly underpriced in a random antique store as often these days. But filtering through buckets (or online listings) of large numbers of coins can still be fun and lead to spotting good deals. So I think there is room in the hobby for nerd-like behavior (per your definition). I would argue the decline of the hobby is more due to competition from other similar hobbies (a generation ago you could collect stamps, coins, baseball cards, or rare books/comics - now you can collect beanie babies, Pokemon cards, NFTs, funko pops, action figures, etc.). I think stamps have suffered more than coins because stamp collecting has more of an aesthetic component (which has faced stronger competition) while coins have a historical element that is less well replicated by collecting newer things. This difference isn't obvious in the google trends graphs you posted but I believe is observable from looking at prices of stamps vs coins. I asked Nathan what coins he collects that are still tough to find, and he gave the example of this Yuan dynasty coin from 1350. I guess if you want to be a collector in 2023 you need to go hard. Arrk Mindmaster writes: I used to collect US coins from every denomination, year, mint, and variety (such as large and small date 1960 pennies). It was kind of like a treasure hunt, knowing you could find something in circulation that was actually more valuable than most people thought it was. I lost interest in the late 1980s sometime, when I found the volume of new coins dwarfed older coins. For example, for Lincoln pennies, they used to make a few million per year, then a few tens of millions. In the 80s, they started making about 5 BILLION each, and it started drowning out all of the old coins, which basically stayed the same value. This comment snapped some things into place for me; I collected coins as a kid in the 90s, and older coin collectors would talk as if you could spot some pretty rare things in your pocket change. But I had much worse luck, and it’s been years since I’ve even found a wheat cent in circulation (even when I was a kid this would happen occasionally). Maybe coin collecting is dying not just because we don’t use change, but because our change is less likely to have interesting coins in it. Another victim of mass money printing! The new state quarters sort of fix this, but other commenters express contempt for this. It feels like the transition between old myths (which one can enjoy) to the Marvel Cinematic Universe (which corporations are begging you to enjoy in a pre-approved way) - now that the Mint wants you to collect their coins, it feels kind of slavish to comply. Other people point out that the collecting of things other than stamps and coins is still going strong. Drethelin: Collecting has not in the slightest died out. People collect more things than ever, like sneakers, funko pops, vintage cars, guns, antique ceramics, anime figurines, magic cards, etc. Some people also brought up NFTs - are there lots of people who truly enjoy collecting NFTs, aren’t just in it for the investment value, and have kept up through the crypto bear market? 4. Comments Insisting That Sports Are Good Aris C writes: It's a little glib to dismiss sports as bad, isn't it? Athletes display extreme skill, sometimes transcendent. I don't think watching people push the limits of human ability is obviously bad. When I said sports were bad, I didn’t mean this as a final value judgment. I meant that, by our usual standards of entertainment, sports are bad. Imagine a sitcom which had several thousand episodes, each with the exact same plot (some people try to get a ball from one side of the court to the other). At some point, surely most people would stop watching! I appreciate the something something human spirit, and I’m happy to know that, somewhere in the world, sports are happening. It’s just the decision to actually watch them that confuses me. 5. Comments About Enjoying Things Vs. Building Identities Around Them Many people complained that some combination of me and/or Sam Kriss were denying that anyone can ever enjoy anything except as an attempt to “gain status”. I would answer first that yes, I think most behavior has some status component (although it may be a small component, mixed with genuine enjoyment). But also, it doesn’t seem mysterious that some people eg like Star Wars, or even love Star Wars. What seems mysterious to me is when this expresses itself as desire to buy thousands of dollars of figurines in the original boxes, or memorize the stats of every class of ship in the Imperial Navy, or something else which doesn’t seem very fun on its own merits. I’m not criticizing others from a place of invulnerability here. When I was ~14, I got really into Star Wars, and aside from reading all the Extended Universe books - some of which were genuinely very good - for about a year I spent all of my allowance and a good fraction of my free time obtaining Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing). My parents probably still have them somewhere. I cannot at all retrace what led me to do this, but I appreciate commenters’ less cynical explanations. For example, enchantingacacia writes: I think it's honestly sort of funny how non-nerds seem to genuinely not understand that a nerd's identity becomes about [thing] because they like it so much, not the other way around. Sometimes you encounter a thing—let's say it's Minecraft, because why not—and it's just such a positive experience for you that you take every possible opportunity to keep thinking about Minecraft, even when you're not playing. You collect every scrap of information you can find about Minecraft and you compose your own original Minecraft-related songs and you decorate your room with blocky little figurines. You get into a virtuous cycle where talking and thinking about Minecraft is so rewarding that you keep enjoying all these secondary activities long after you're bored of actually playing Minecraft itself. You look out for opportunities to meet people who'd enjoy talking about Minecraft with you and make a bunch of friends with whom you mostly talk about Minecraft, and your friends and family start seeing you as "the Minecraft guy" and they get you a Minecraft hoodie for Christmas cause they know it's a safe pick. This is the obvious and intuitive explanation! There's no need to get fake-deep about "ah, they got into Minecraft so they'd have something to construct their identity around": it explains nothing, and consistently makes incorrect predictions about the internal experiences of Minecraft nerds. It's only virtue is making people feel better about being annoyed by those weirdos who won't shut up about Minecraft. It's possibly that I have unusually low social motivation (genuinely, what does it mean to "construct your identity" and why is it something people would be this comically desperate to do?) and am typical-minding, but, uh, I wonder if there's any group closely associated with "nerds" who are also known for having low social motivation? I think it's a tad more likely that people like Kriss are typical-minding, and constructing elaborate social motivations for people who just like stuff regardless of what people like him think. This is a good comment which avoids buck-passing-style “I enjoy it because it’s fun” explanations. Along the same lines, odd anon writes: It is only among nerds that enthusiasm for something corresponds to learning more and more about it. That's the core element here. Non-nerds who like something do not feel any need to read up on it, to know more and more. Of course, the producers of content notice when their audience are nerds, and they start to produce content built more for those who obsessively learn every detail. Comics can start "rewarding" readers for noticing some obscure thing. A game series can have an elaborate continuity, or a zillion details to memorize. Content that either "leans into the fandom" or simply naturally has too much for non-nerds to easily pick up, can rapidly become nerd-only, thus solidifying boundaries. And sure, there are the personality correlations, attributes most nerds also have, including being STEM-y and lacking social skills. Combined, a nerd ended up being an unpopular thing to be. Ghatanathoah is less patient: Both Kriss' essay, and Scott's response to it, remind me of the "Evil Cannot Comprehend Good" trope from TV tropes, except replace "Evil" with "Very socially motivated people" and "Good" with "Less socially motivated people" (although honestly both sets have a lot of overlap). Both essays seem obsessed with finding some deep, social reason why hipsters and nerds behave the way they do, like the supervillain who is telling the hero that they are "Not So Different." They literally can't comprehend the idea that someone could actually like something, so they try desperately to find some way that liking things isn't something people actually do. People couldn't actually like Star Wars, sportsball, the MCU, or the Beatles, they must be liking them to achieve some social goal like forming an identity or seeking status! This is one of the two giant flawed assumptions that invalidates the theses of both articles (the other one, of course, is the assumption the the MCU is bad, when it is, in fact one of the human race's greatest artistic achievements*). If you assume that it is possible to like things for non-social reasons, or even in addition to social reasons, hipsters and nerds make much more sense. The reason that nerds like both popular stuff like the MCU, and less popular stuff like postage stamps is because they don't care about if something is popular, they care about if it fascinates them. Whether that thing is popular is orthogonal to how fascinating it is. That fascination makes them invest a lot of time and effort in it, which in turn makes it part of their identity. They weren't trying to find something to form and identity first and picking Star Wars, identity formation was just a side effect. Similarly, hipsters probably just get bored with things they see frequently and want to seek out new things to be interested in. Making obscure things part of their identity comes second, if at all. Also Ghatanathoah: Scott asks if its ever okay to build your identity around liking a thing. I would ask if it's ever okay not to? What's the alternative, building it around social status games or large nonselective identity groups? It seems to me that liking something isn't just a good thing to build your identity around, it's one of the best things to build it around. After all, unlike social status games, you can like something without forcing other people to not like it. This is a good question, well-phrased. I think the traditional answer is that you should build your identity around social relationships (I’m the son of X, husband of Y, friend of Z), career, and maybe a few hobbies. I agree with this as far as it goes, but it doesn’t work for a lot of practical tasks - I can’t get common ground with someone at a party or start a conversation by introducing myself as the son of X or husband of Y - most people just won’t know X or Y. Some people linked a Freddie de Boer post, Your Personality Has To Be Load-Bearing, which is generally good but I think has a similar problem. Obviously you should have a genuine and complex personality, but I worry a lot of people who talk about this will reject every specific aspect of personality because “it’s not, in itself, a full complex personality!”, but you can’t have a personality without building it out of specific aspects. A lot of people’s default personality, if they just do exactly what comes naturally and don’t put any effort into self-presentation or cultivation, is to browse Reddit and play video games. Most people realize this on some level and try to cultivate some personality beyond this, but I think that makes it extra unfair to say “Just use your natural true self!” The natural true self is exactly the boring thing we’re trying to get away from in favor of becoming a more interesting person. I’m trying to think if I have a personal answer to this. Part of my answer is the EA and rationalist communities. This has some downsides; I’m thinner-skinned about insults to these groups than I should be; some people might think I’m a fanatic. It also has some upsides; they embody real values I like, they try to make a difference in the world, they’re not consumer properties that make me feel like a corporation is pulling my strings. But my real answer is probably “I cheat by having a popular blog; this means you all know everything about me and I don’t have to fit my personality into a ten-second elevator pitch”. Maybe this is the traditional solution, from back when everyone knew everyone else in their community. It sure doesn’t feel adequate now, back when (non-bloggers) are constantly meeting strangers and having to communicate their identity to them quickly. My internal hierarchy of things it’s virtuous to build identity around, which is probably a weird class artifact and which I absolutely don’t consciously endorse, goes something like: Top-tier: Intellectual subfields, especially obscure ones or ones involving pure abstract math. If you can say “I’m really into trans-finite 8-dimensional Hoffdorf groups” and justify this with a discussion of how innately beautiful they are, you’ve got it made.
January 13, 2026 · Original source
“I started a data center company in Minecraft”.
“Oh, sorry, I’m not using ‘in Minecraft’ as a euphemism for it being a crime. We’re literally building the data centers in Minecraft.”
“Did you hear about the guy who made a working language model in Minecraft using redstone circuits? Pretty amazing, isn’t it? His version is barely GPT-2 level, but there’s no reason we can’t scale that up. Once we create full-sized data centers in Minecraft, everyone will want to do their training runs there.”
Nootropics Depot

Nootropics Depot is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 28, 2021 and October 05, 2022. The archive places it in contexts such as "Nootropics Depot's Dynamax, a mixture of several fancy types of caffeine and caffeine-like chemicals"; "Nootropics Depot is on a crusade to test whether other supplements are correctly labeled"; "Nootropics Depot is a supplement company that actively engages with the supplement community on Reddit". It most often appears alongside Reddit, turkesterone, Wikipedia.

Article page
Nootropics Depot
Mention count
3
Issue count
3
First seen
April 28, 2021
Last seen
October 05, 2022
April 28, 2021 · Original source
Results were generally predictable and unexciting (with one exception I'll get to soon). People thought stimulants worked better than non-stimulants, addictive substances better than non-addictive substances, and well-known mainstays better than new experimental chemicals. As on previous surveys, branded combination pills did worse than individual substances. For example, Nootropics Depot's Dynamax, a mixture of several fancy types of caffeine and caffeine-like chemicals, did significantly worse than ordinary caffeine. Nootropics Depot has a lot of smart, careful people, so I don't think they bungled the mixture. I think people just expect more out of branded products, and penalize them when they don't perform better. Since all tests were open label, I have no way of knowing how much of the results were just expectation effects.
3 recs: ModafinilXL, CosmicNootropic 4 recs: Liftmode 5 recs: Eufinil 6 recs: Science.bio 7 recs: BuyModa, LiftMode 48 recs: Nootropics Depot
July 01, 2022 · Original source
46: Nootropics Depot is on a crusade to test whether other supplements are correctly labeled. Here’s what happened with turkesterone.
October 05, 2022 · Original source
I looked through several other supplements on these sites and these results are typical, although maybe slightly better than average. The most concerning category was mushrooms, where about 25% of brands used some mycelium (the “roots” of a mushroom, which have fewer health-promoting chemicals than the above-ground part) instead of or in addition to the mushroom itself. This is a known issue with mushroom supplements; not enough people know the difference for companies to be consistently incentivized to get it right. III. MYASD From Nootropics Depot Nootropics Depot is a supplement company that actively engages with the supplement community on Reddit. A big part of the engagement is their CEO, who goes by the Reddit username MisterYouAreSoDumb, talking about his experiences running the company and answering customer questions.
Nootropics Depot is a supplement company that actively engages with the supplement community on Reddit. A big part of the engagement is their CEO, who goes by the Reddit username MisterYouAreSoDumb, talking about his experiences running the company and answering customer questions.
Botanicals are more complicated. Commonly-used botanicals from reputable brands are usually about as trustworthy as vitamins, but there are lots of complications around extraction processes and sometimes you might get 50% more or less than you thought. Less-commonly-used botanicals are less clear; you still will rarely find outright sugar pills, but you may find people bungling the chemistry, not caring too much about exact amounts, or selling mushroom mycelium instead of fruiting body. “Male enhancement” products are their own special class of danger zone, as are anything that’s been featured on The Joe Rogan Experience; you should be extra careful to buy from only the most reputable companies. I trust Nootropics Depot, Thorne, NOW, and Jarrow, in that order, but you’ll want to do your own research and maybe check ConsumerLab for the particular product you’re buying.
OKCupid

OKCupid is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 18, 2021 and February 14, 2023. The archive places it in contexts such as "When I was dating more, I had some success using OKCupid, where most people would write long essays about who they were and what kind of relationship they wanted"; "I'm still mad about OKCupid"; "OKCupid managed it for a few years". It most often appears alongside facebook, FDA, match.com.

Article page
OKCupid
Mention count
3
Issue count
3
First seen
May 18, 2021
Last seen
February 14, 2023
May 18, 2021 · Original source
When I was dating more, I had some success using OKCupid, where most people would write long essays about who they were and what kind of relationship they wanted. Tinder was always more of a mystery; usually just a photo plus a one-sentence cryptic description like “25, Aquarius, hit me up! <3” I sometimes considered lowering my standards enough to “swipe right” on one of these people, but was never actually able to sacrifice that amount of dignity. Then OKCupid became a much worse Tinder clone and my useful options collapsed to zero (don’t worry, I’ve since found someone great through my community). While in theory dating apps are a great solution to this problem, in practice they’re surprisingly terrible.
November 05, 2022 · Original source
Apparently our incumbent representative on the Santa Clara Valley Water District is the founder of match.com?? I feel like I have to vote against him because I'm still mad about OKCupid.
February 14, 2023 · Original source
Presumably Aella will seriously look into the top few candidates, and try asking them out. Why is this good? Consider Aella’s perspective: she can log off for a few weeks, then check back and see a ranked list of who the Internet thinks she’s most compatible with. It’s kind of like asking your friends for dating recommendations, except with better incentives on your friends’ part to predict exactly how likely you are to get along with each candidate. The current leading candidate (in blue) is Steven Bonnell aka Destiny, a famous streamer. I don’t know if he is actually especially compatible with Aella, or if he just has a lot of fans on Manifold who like him and are rooting for him to date someone, or who think it would be funny to add his name in. It wouldn’t surprise me if this worked for Aella; she’s famous and probably dates other famous people; enough people know her and her potential partners that it’s worth crowdsourcing recommendations. What about the rest of us? I was able to find one non-famous person who made a market like this, apparently with good effect, but they seemed awkward enough about it that I’m not going to link it here or provide more details. Non-famous people realistically have easier ways to ask their friends, but I still think this provides value. Sadly, Porn talked about the “omniscient authority” - asking someone on a date is so scary that people want to pretend their normal human psychological needs had no input into the decision - “It’s … not like I … like you or anything, baka! I’m just doing this because I - a pure abstract intelligence who is not horny for you in any way - was informed by friends/matchmakers/our OKCupid match percentage/’the algorithm’/a dream, that asking you on a date was my duty, which I now dispassionately fulfilling.” A prediction market would make a great omniscient authority here. Also, consider the implications for romance stories. I’ve only thought about this for five minutes, so I definitely haven’t exhausted the space, but I imagine: Someone does some kind of complicated financial fraud to manipulate a prediction market into telling their crush to date them. Think Wolf Of Wall Street, but a rom-com.
Somehow this never happens. OKCupid managed it for a few years, and then Match.com bought it, murdered it, and gutted the corpse. Now it’s just a wasteland of Tinder clones, forever. Sure, Luna’s rectification of the financial incentives is clever, but it seems like there’s been some kind of more fundamental failure. Why can’t we have the normal low-tech version? Why are things so bad that the people I know have been reduced to manually making profiles on Google Docs and listing them on an online spreadsheet?
Oxfendazole

Oxfendazole is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between November 04, 2022 and June 18, 2025. The archive places it in contexts such as "Develop Oxfendazole As A New Deworming Medication"; "Development of oxfendazole, a drug for treating parasitic worms"; "Antiparasitic medication oxfendazole continues to advance". It most often appears alongside Manifold Markets, 1DaySooner, acanthamoeba keratitis.

Article page
Oxfendazole
Mention count
3
Issue count
3
First seen
November 04, 2022
Last seen
June 18, 2025
November 04, 2022 · Original source
11: Develop Oxfendazole As A New Deworming Medication (10/10) The Oxfendazole Development Group has received a further $1.6 million from Open Philanthropy. They have completed several studies on metabolites and drug interactions, and are working on more. It is still early in the approval process but they are optimistic. They are looking for further funding to better characterize the physical/chemical properties of oxfendazole; contact here if you are able to help.
Oxfendazole Development Group is looking for more funding; contact them here if interested.
December 08, 2023 · Original source
Development of oxfendazole, a drug for treating parasitic worms in developing countries.
June 18, 2025 · Original source
11: Develop Oxfendazole As A New Deworming Medication
Drug development is a highly regulated process; it is not glitzy. But this necessary path to bring a new medicine to deworming efforts world-wide is no the less important because of having to follow a prescribed pathway. To this end and because of the largesse of donors, we have completed several nonclinical studies on oxfendazole itself, on its physical chemical properties, and on its potential for toxicity in a rodent and a non-rodent species.
These studies support our clinical work, following successful completion of two Phase I studies. We are presently collaborators on three Phase II efficacy studies taking place in Peru on three different parasitic diseases, an approach to ascertain the range (in terms of disease and dose) of oxfendazole’s efficacy.
OxyContin

OxyContin is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between August 21, 2023 and April 25, 2024. The archive places it in contexts such as "Arguing about gender is like taking OxyContin"; "People didn’t worry enough about ... OxyContin". It most often appears alongside Aella, San Francisco, 1990s.

Article page
OxyContin
Mention count
3
Issue count
3
First seen
August 21, 2023
Last seen
April 25, 2024
August 21, 2023 · Original source
Arguing about gender is like taking OxyContin. There can be good reasons to do it. But most people don’t do it for the good reasons. And even if you start doing it for good reasons, you might get addicted and ruin your life. Walk through San Francisco if you want to see people who ruined their lives with opioids; browse Substack to get a visceral appreciation of the dangers of arguing about gender.
August 30, 2023 · Original source
Arguing about gender is like taking OxyContin. There can be good reasons to do it. But most people don’t do it for the good reasons. And even if you start doing it for good reasons, you might get addicted and ruin your life. Walk through San Francisco if you want to see people who ruined their lives with opioids; browse Substack to get a visceral appreciation of the dangers of arguing about gender.
April 25, 2024 · Original source
But - even granting that there are many cases of both - are these useful? There are many cases of moral panics turning out to be nothing. But there are many other cases of moral panics proving true, or of people not worrying about things they should worry about. People didn’t worry enough about tobacco, and then it killed lots of people. People didn’t worry enough about lead in gasoline, and then it poisoned lots of children. People didn’t worry enough about global warming, OxyContin, al-Qaeda, growing international tension in the pre-WWI European system, etc, until after those things had already gotten out of control and hurt lots of people. We even have words and idioms for this kind of failure to listen to warnings - like the ostrich burying its head in the sand.
paroxetine

paroxetine is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between March 31, 2021 and February 29, 2024. The archive places it in contexts such as "16.7 mg Lexapro equals 20 mg of paroxetine (Paxil)"; "It did significantly better than paroxetine"; "SSRI called paroxetine (Paxil)". It most often appears alongside SSRIs, FDA, @BoyanSlat.

Article page
paroxetine
Mention count
3
Issue count
3
First seen
March 31, 2021
Last seen
February 29, 2024
March 31, 2021 · Original source
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
Prozac: 30 mg Paxil: 30 mg Zoloft: 75 mg Celexa: 30 mg Lexapro: 15 mg
May 18, 2022 · Original source
So fine, let’s look at the studies. A typical example is Kaspar (2014), Lavender oil preparation Silexan is effective in generalized anxiety disorder. It has 539 people, which is really quite impressive - usually these kinds of supplement trials would have more like 10% of that. The study is double-blind (patients don’t know if they’re getting silexan or placebo, and doctors don’t know which one they’re giving) and they made sure the placebo capsules smelled like lavender (a nice touch!) The groups were randomized carefully, but there were some statistically significant random differences between them; none of them seemed too worrying to me but your opinion might differ. There was a clear, obvious, and dose-dependent effect of silexan vs. placebo (p < 0.001) on seven of eight outcomes measured; the eighth was “physical health” and it’s fine if an anxiety drug doesn’t help with this (although you could always hope it would relieve some ailments by making people less stressed). It did significantly better than paroxetine, which only reached statistically significant effect size on about half of the outcomes (par for the course in these kinds of studies, SSRIs are kind of weak). Effect size was 0.37 for the 80 mg dose, and 0.5 for the 160 mg dose.
February 29, 2024 · Original source
SSRIs usually are an option during pregnancy . . . risks include high blood pressure for the pregnant person and premature birth. These risks are small. Your health care team watches for them during your prenatal care. Most studies show that SSRIs aren't linked with birth defects. But an SSRI called paroxetine (Paxil) might slightly raise the risk of heart defects in babies when used during the first trimester.
Reciprocity

Reciprocity is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 14, 2023 and January 13, 2026. The archive places it in contexts such as "Our version of the matching checkbox site, https://www.reciprocity.io/"; "A checkbox/swipe feature like on Reciprocity or Tinder"; "I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing". It most often appears alongside Tinder, Harvard, OKCupid.

Article page
Reciprocity
Mention count
3
Issue count
3
First seen
February 14, 2023
Last seen
January 13, 2026
February 14, 2023 · Original source
The rationalist community has many advantages here - it’s a well-bounded, closely connected group of people who are all interested in experimenting with weird social technology. Our version of the matching checkbox site, https://www.reciprocity.io/, has solved the onboarding problem; most rationalists have accounts, though you’ll need to be Facebook friends to see some of them.
That brings us to the second problem: complicated preferences. There are plenty of stories of someone checking someone on Reciprocity, not getting a mutual match, then asking them in person and they say yes. I’ve written more about this here, but I think the basic problem is that people can either be excited, lukewarm, or hostile towards each other. And a lot of people would be interested in trying a date with someone they’re lukewarm towards as long as that person is excited about them, but they don’t want a date where both of them are lukewarm. And there’s no consistent checkbox behavior that will create all excited-lukewarm relationships but no lukewarm-lukewarm relationships.
Unfortunately, it’s now common knowledge that people will sometimes say yes in person when they haven’t checked you on Reciprocity, which means you’re back to having to decide whether or not to ask your crush on a date. Tragic!
November 03, 2023 · Original source
A checkbox/swipe feature like on Reciprocity or Tinder, where if you were too chicken to ask someone out directly, you could click a box saying you liked them, and if they clicked the same box on you, you would match. I’m a little skeptical of these for reasons described here, but maybe you could fix it by having separate “excited to date this person” and “willing to try dating this person if they were excited about dating me” levels of box-tick.
January 13, 2026 · Original source
Chris is looking dejected. “Man, I haven’t even made it to engaged-stage-zero yet. I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing. Do you think I should edit my dating doc?”
silexan

silexan is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 18, 2022 and May 29, 2024. The archive places it in contexts such as "silexan (derived from lavender) has started to stand out of the crowd"; "Silexan has four meta-analyses, all of which show strong effects"; "Lavender oil preparation Silexan is effective in generalized anxiety disorder". It most often appears alongside Israel, Latin America, Twitter.

Article page
silexan
Mention count
3
Issue count
3
First seen
May 18, 2022
Last seen
May 29, 2024
May 18, 2022 · Original source
1: What is silexan?
But recently silexan (derived from lavender) has started to stand out of the crowd. Daily Mail had an interview with psychiatry professor Hans-Peter Volz, who said that silexan should be first-line for anxiety, replacing things like SSRIs and Xanax. And a very reputable professional publication within psychiatry, The Carlat Report, published an article and a podcast touting silexan:
Not many treatments in psychiatry have a large effect size. There’s stimulants for ADHD, ketamine for depression . . . and now Silexan for generalized anxiety disorder.
February 01, 2023 · Original source
But in other fields - the one that comes to mind now is declining sperm count, which I’m trying to write an article on - there aren’t the equivalent of Phase 3 trials. Just a hodgepodge of smaller or bigger studies, probably about as good as the ones that find ivermectin improves viral clearance, producing a hodgepodge of noisy results. Then some statistician draws a line through the noise and tells us the line is pointing up and that means we should be worried. Should we? What about silexan for anxiety? There are five studies - better than the worst ivermectin studies, but nowhere close to Phase 3 - and they find positive results. Silexan would revolutionize the treatment of anxiety and help avoid medications with much worse side effects. Do I start recommending it as a first line treatment?
May 29, 2024 · Original source
32: A while back I wrote about studies supporting the supplement silexan for anxiety. Now there’s a new study saying it works for depression - but it’s still by the same group that did all the previous positive studies. I will be more excited when I see a positive study from anyone else.
Solana

Solana is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between August 16, 2022 and February 29, 2024. The archive places it in contexts such as "Hedgehog Markets is a crypto betting site using USDC and Solana"; "you need to have a Solana wallet"; "some kind of trading in Solana (a cryptocurrency)". It most often appears alongside AI, China, Hanania.

Article page
Solana
Mention count
3
Issue count
3
First seen
August 16, 2022
Last seen
February 29, 2024
August 16, 2022 · Original source
Hedgehog Markets is a crypto betting site using USDC and Solana. Most of its markets are about sports. I’m featuring them here because they are, as far as I know, the first group to do something I’ve been waiting for a long time - allow users to create real-money prediction markets.
What’s the catch? Offer not open to US citizens - a vexing, problematic negation. And you need to have a Solana wallet, own crypto, and know how to use it. And there’s not a lot of volume so far. But otherwise, no catch. This is just a really good new thing. Think of it as Manifold Markets, but with real money (and 10x harder to use).
February 20, 2024 · Original source
4: A DAO (a type of crypto organization) claims to be implementing futarchy. It’s less clear what they’re implementing futarchy to do, but I think it’s some kind of trading in Solana (a cryptocurrency).
February 29, 2024 · Original source
52: According to NYT, during his time in prison Sam Bankman-Fried has tried to convince the guards to buy the Solana cryptocurrency. In fairness to him, it’s gone up in value about 10x since his arrest. That means there’s some prison guard who got a hot tip from SBF to put his net worth in Solana, laughed because of course you don’t take investing advice from SBF, and then had to watch while as it dectupled in price over the next year.
StableDiffusion

StableDiffusion is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between September 12, 2022 and February 29, 2024. The archive places it in contexts such as "StableDiffusion: 0/5"; "random nobody startups came out with StableDiffusion"; "I recommend this StableDiffusion video by Herolias". It most often appears alongside China, Google, GPT.

Article page
StableDiffusion
Mention count
3
Issue count
3
First seen
September 12, 2022
Last seen
February 29, 2024
September 12, 2022 · Original source
Stability.ai StableDiffusion announced August 2022.
StableDiffusion: 0/5
March 01, 2023 · Original source
DeepMind thought they were establishing a lead in 2008, but OpenAI has caught up to them. OpenAI thought they were establishing a lead the past two years, but a few months after they came out with GPT, at least Google, Facebook, and Anthropic had comparable large language models; a few months after they came out with DALL-E, random nobody startups came out with StableDiffusion and MidJourney. None of this research has established a commanding lead, it’s just moved everyone forward together and burned timelines for no reason.
February 29, 2024 · Original source
17: There’s a verse in Chesterton’s Lepanto where he describes the ascended spiritual Mohammed as having a “turban that is woven of the sunsets and the seas”. If you’ve ever wondered what that would look like, I recommend this StableDiffusion video by Herolias (warning: flashy, might be bad for epilepsy, you might have to go very close and/or very far from your computer to get the full effect). I recommend pausing mid-video to see how innocuous each frame looks on its own).
Stripe

Stripe is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 19, 2021 and April 17, 2023. The archive places it in contexts such as "celebrity special guests including ... Stripe’s Patrick Collison"; "using normal microtransactions with Visa or Stripe or whatever"; "I don’t know how hard it is to do through Stripe". It most often appears alongside PolymorphicWetware, ACX, ACX.

Article page
Stripe
Mention count
3
Issue count
3
First seen
April 19, 2021
Last seen
April 17, 2023
April 19, 2021 · Original source
3: Joshua Fox wants to remind you that there are still ACX online meetups scheduled at least until June, with various celebrity special guests including Qualia Research Institute’s Andrés Gómez Emilsson, Stripe’s Patrick Collison, and meditation expert Daniel Ingram. Check out https://joshuafox.com/ssc-online-meetups/ for more information or to sign up. I’ve added this to the blogroll so you don’t forget about it.
February 14, 2023 · Original source
You could probably solve both problems just by cutting out the cryptocurrency angle and using normal microtransactions with Visa or Stripe or whatever. I think there’s still a risk that “get paid for [thing related to dating]” seems too creepy and sex-work adjacent and respectable women might avoid it; maybe you should instead let the woman donate the money to a charity of her choice?
April 17, 2023 · Original source
3: I’ve recently been confronted with the question of whether or not to ban (including permaban) paid subscribers who break rules. I don’t want to create a class system where richer people are above the law, but it also seems harsh to take your money and then prevent you from using the service you paid for. My working solution will be to err towards not banning paid subscribers (or banning them for less time) in edge cases, otherwise ban them if they earn it, and refund subscription costs to anyone banned if they ask for it. I haven’t tried this yet, I don’t know how hard it is to do through Stripe, and I might ask you for Paypal if I have to. Being banned doesn’t mean I don’t like you or appreciate your support, just that the comments section is degenerating quickly and I really want to push back against that.
suboxone

suboxone is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 24, 2022 and February 09, 2023. The archive places it in contexts such as "I support suboxone treatment"; "three-quarters receiving an opioid substitute like methadone or Suboxone, the brand name of buprenorphine"; "Shellenberger as opposing suboxone treatment and supporting “sweeping institution” of the mentally ill". It most often appears alongside California, Newsom, San Francisco.

Article page
suboxone
Mention count
3
Issue count
3
First seen
May 24, 2022
Last seen
February 09, 2023
May 24, 2022 · Original source
But like many people who have original opinions, he also gets some things really wrong. On his mental health-related opinions - the rare field I am qualified to assess - he comes to opposite conclusions from me. I support suboxone treatment , he’s against it; I oppose sweeping institutionalization of the mentally ill, he’s for it [EDIT: Shellenberger has objected to this characterization of his position and says he believes the opposite of what I ascribed to him] . Also, he wants the school day to be longer in order to be more convenient for parents, which is thoughtful and makes sense, but only in the same way that never letting people out of prison would be more convenient for parole boards. Lots of hits, lots of misses.
June 23, 2022 · Original source
Results of a survey at one of SF’s new Navigation Centers at why their clients refused to go to normal shelters. But even the homeless people who do want to go to shelters mostly can’t get in. This app gives the current status of San Francisco’s homeless shelter waitlist. If you applied today, there would be 900 people ahead of you in line for one of the city’s 1500 - 2500 shelter beds. The app says that the median wait time is 826 days. So however many homeless people don’t want to go to shelters, we’re not building enough shelters to serve the ones who do. Why not? Shellenberger again: In the spring of 2021, Friedenbach published an op-ed opposing a proposal considered by the San Francisco Board of Supervisors to create, within eighteen months, sufficient homeless shelters and outdoor “Safe Sleeping Sites” for all of the city’s unsheltered homeless. “One can simply take a look to New York City,” she wrote. “Their department spends about $1.3 billion dollars of its budget on providing shelter for their unhoused population while thousands remain on the street. . . . As a result, New York has a higher rate of homelessness than San Francisco.” Housing First advocate Margot Kushel of the University of California, San Francisco agreed. “The problem with New York—and I spend a lot of time with people working in the system in New York—is that they spend an estimated $30,000 for each person per year to keep them in shelter. That’s not what we want to do. Because if you create the shelter and you don’t create the housing, then people are just in shelter forever.” Housing First advocates oppose shelter in Los Angeles. “Why haven’t we solved homelessness?” asked Housing First creator Sam Tsemberis. “Because [Los Angeles mayor] Eric Garcetti [has] Andy Bales [saying,] ‘You need emergency housing.’ ‘These people need to be cleaned up.’ ‘They need to be sober.’ ‘They need Jesus before they’ll be ready for housing.’ I said, ‘People should be housed and then maybe they’ll get sobriety and Jesus and the rest.’ We’re definitely on polar opposites of the whole thing.” Advocates for the homeless at the national level similarly oppose more shelters. “I don’t agree that we should be building more transitional housing,” said the head of the National Alliance to End Homelessness. […] In other words, the reason that there are so many homeless people on the streets in San Francisco is that both progressive and moderate Democratic elected officials, and the city’s most influential homelessness experts and advocates, have for two decades opposed building sufficient shelters. And that is unlikely to change even after San Francisco starts spending hundreds of millions more per year on the problem and might even get worse. This basically seems true. I found this webpage of a former SF Supervisor candidate a helpful corroborating source. He was running on a platform of “maybe we should build some homeless shelters”. He lost. You can also find a bunch of webpages by the sorts of people Shellenberger is complaining about, for example this site: Sup[ervisor] Rafael Mandelman today pushed his new legislation that would require the city to offer at least temporary shelter to everyone living on the streets, a step that some say would lead to more homeless sweeps and do nothing to create permanently affordable housing . . . [our] Coalition has argued for years that the solution to homelessness is housing—not temporary shelter, which may never lead to housing. The ex-supervisor candidate gives some helpful numbers: permanent housing costs about $600,000 per person housed. Shelters cost between $20,000 and $30,000 per person housed. So SF could build enough shelters to clear its waitlist for about $30 million. More recently, SF has tried a sort of compromise, opening “deluxe” shelters called Navigation Centers which avoid some of the problems of regular shelters. They also cost more than twice as much, and the city has only created about 300 beds. Also, the people in regular shelters are angry, because being in a regular shelter disqualifies you from getting into a (much better) Navigation Center. Some of them are considering leaving their shelter, going back on the streets, then waiting however many months or years it takes to get a Navigation Center bed instead. I’m not at all sure of these numbers, but it looks like of SF’s ~7,000 homeless, about 2,000 are in shelters already, and 1,000 are on the shelter waitlist. I don’t know if the remaining 4,000 have made a specific commitment not to go to shelters, or just have given up on the waitlist process. My conclusion: agree with San Fransicko about the role of progressive activists, but I think it overemphasizes the role of wanting to use drugs in why homeless people themselves sometimes avoid shelters, and underemphasizes the many other problems with them. Claim 5: Drug Decriminalization Isn’t Working California legalized marijuana in 2016. Shellenberger says that San Francisco’s commitment to drugs has gone beyond that: it has effectively decriminalized opioids, cocaine, and the rest. Any attempt to lessen use of these drugs is attacked as “stigmatizing”; instead, government policy centers around providing addicts with needles and other drug paraphernalia under the guise of “harm reduction”. Shellenberger hits all the right beats here. Like many people, he tries to undo the damage done by The New Jim Crow, a book which convinced millions of people that mass incarceration was driven by a racist War On Drugs. In fact, less than a fifth of prisoners are in for drug-related crimes. And when the government was first debating the War on Drugs and mass incarceration, black leaders were among the strongest proponents of both. The talking point at the time - among everyone from black Congressional leaders to black churches - was that the government’s failure to crack down on drug use was racist, borne of them not caring about predominantly black drug victims. And while we’ve been patting ourselves on the back about how enlightened we are for ending the drug war: Drug overdoses are today the number one cause of accidental death in the United States as a result of America’s historic addiction and overdose epidemic. Overdose deaths rose from 17,415 in 2000 to 93,330 in 2020, a 536 percent increase.Significantly more people die of drug overdoses today than of homicide (13,927 in 2019) or car accidents (36,096 in 2019). […] There are about twenty-five thousand injection drug users in San Francisco, a number 50 percent larger than the number of students enrolled in the city’s fifteen public high schools. San Francisco gives away more needles to drug users, six million per year, than New York City, despite having one-tenth the population. The part of this chapter that stood out to me as most worth looking into deeper was the section on Portugal: For decades, harm reduction and decriminalization advocates have pointed to Portugal as a model, noting that it decriminalized drugs and expanded drug treatment. In 2013, Portugal’s drug-induced death rate was sixty-six times less than that of the United States. The number of people in treatment increased by 60 percent between 1998 and 2011, with three-quarters receiving an opioid substitute like methadone or Suboxone, the brand name of buprenorphine. Drug use among 15- to 24-year-olds actually declined after decriminalization. “All drugs have been legalized,” explained Monique Tula, executive director of the Harm Reduction Coalition. “Their focus is on giving people tools, like job apprenticeships, and the means to support themselves.” […] [But Portugal] never legalized drugs. It only decriminalized them, reducing criminal penalties but maintaining prohibition. Drug dealers were still sent to prison even after the 2001 decriminalization. And Portugal does not let people addicted to hard drugs with behavioral disorders off the hook like progressive West Coast cities have done. It’s true that Portugal massively expanded drug treatment, but people are still arrested and fined for possession of heroin, meth, and other hard drugs. And drug users are typically sent to a regionally administered “Commissions for the Dissuasion of Drug Addiction,” composed of a social worker, lawyer, and doctor who encourage, push, and coerce drug treatment. And decriminalization doesn’t end drug violence. “Even if trafficking enforcement decreased, like it did in Portugal,” said criminologist John Pfaff, “illegal drug markets would still be forced to rely on violence to resolve disputes.” Indeed, prostitution and violence are ever-present in the open-air drug scenes in San Francisco, Los Angeles, and Seattle. “We are seeing behaviors from our guests that I’ve never seen in thirty-three years,” said Rev. Andy Bales, who runs the largest homeless shelter on Skid Row in Los Angeles. “They are so bizarre and different that I don’t even feel right describing the behaviors. It’s extreme violence of an extreme sexual nature.” People are not dying from drug overdose deaths in San Francisco because they’re being arrested. They’re dying because they aren’t being arrested. Decriminalization reduces prices by lowering production and distribution costs, which increases use. This was also the case for alcohol consumption. It increased after prohibition ended in the United States. Even in Portugal, drug overdose deaths and overall drug use rose after decriminalization. I was most surprised by the claim that Portuguese overdose deaths rose after decriminalization. Uncharacteristically, San Fransicko doesn’t give a citation for it, but we can try to retrace its reasoning. Decriminalization proponents tend to point to these numbers, helpfully converted to per 100,000 population and graphed here: But an anti-drug Australian think tank argues that the peak in 2001 is made up: Claims that there were more than 75 drug-related deaths in 2001 which more than halved to 34 deaths in 2002 use a figure for 2001 for which there is no substantiation. Official drug-related deaths for Portugal, taken from the latest 2018 EMCDDA Statistical Bulletin are copied below. Notice that there is no such figure recorded for 2001. They include a link to EMCDDA, the EU organization charged with monitoring these things. The link contains two datasets, both of which seem to be measuring the same thing but getting different results. One dataset starts in 2002, the other in 2008. I don’t know what the difference here is, but they’re right that neither includes 2001. If you ignore the pre-2002 data, the graph looks like this: They say “opiate”, but AFAICT these numbers are actually about all drugs. But the proponents link to the updated 2020 version of the same website, which all of a sudden does have data from 2001 and before. I don’t know why EMCDDA can’t make up its mind, but I think the Australians are wrong and the original graph is fine. On the other hand, does it really matter? Both of these show drug deaths decreasing until 2005, then going up and down a bit, then going back up again starting in 2011. I think a reasonable interpretation would be that decriminalization in Portugal did decrease overdose deaths a bit, and then they started rising again from that low baseline around the same time other European countries saw rising overdose deaths. I would also accept “these are pretty small effects and we shouldn’t ascribe any significance to them”. But San Fransicko’s claim - that overdose deaths increased after the reform - seems false. The only way I can see justifying it is taking the second graph - the one that wrongly claims there is no pre-2002 data - and then attributing the fact that twelve years after the reform lowered deaths, deaths finally rose above the pre-reform level to be the fault of the reform. This is like saying “people claim the Black Plague killed a lot of Europeans, but the European population actually rose after the Plague”, which is true in the sense that it was above its pre-Plague max by like 1600 or whatever. What about overall drug use? Here I recommend A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs, which is on exactly this topic of how people keep selectively quoting results from Portugal to prove their point. It argues that drug use is inherently hard to measure. There are four different Portuguese datasets for the time at issue, lots of different drugs, lots of different age/gender combinations, and lots of different ways of measuring drugs (did you use drugs in the past month? the past year? your lifetime?) It’s easy to tell a story of how past-month cocaine use skyrocketed among 14-29 year old males according to X source, or how lifetime marijuana use fell in high school-age women according to Y. The main trick that opponents use is measuring lifetime drug use. Portugal is a very conservative country; drug use is pretty new and most of the older generation wasn’t involved. So as time goes on and more and more people try drugs but “un-trying” drugs isn’t a thing, the percent of the population who have tried drugs inevitably goes up. This definitely happened but isn’t a fair reflection of any specific reform. The authors find that in the past decade or so, there has been a bit more short-term experimentation with drugs, but less long-run use. They conclude: As shown in Figure 2, general population (aged 15–64) trends for recent and current drug use in Portugal indicate minimal if any changes between 2001 and 2007. Instead, rates of discontinuation of drug use (the proportion of the population that reported ever having used a drug but opting not to in recent years) increased, which reinforces that just as in the school populations, the growth in lifetime-reported use reflected predominantly short-term experimental use. Increases in recent and current drug use were more notable in some cohorts, particularly those aged 25 to 34 (albeit, with a maximum of 7% of any one cohort reporting recent use, absolute levels remained low). But as shown in Figure 3, recent and current drug use declined among those aged 15–24, the population who were most at risk of initiation and long-term engagement. The available evidence thus gives grounds for arguing that while there was some growth in the scale of drug use in post-reform Portugal, there was an overall positive net benefit for the Portuguese community. What about San Fransicko’s main point - that as the US has wound down the War on Drugs, drug overdose rates have sextupled? I think this is mostly not causal. I think the sextupling of overdoses is a combination of expansion in prescription opioid use, various forms of social decay making people less happy and therefore more likely to use drugs, and “improvements” in drug “technology” and the “supply chain” (eg production of fentanyl in China). I don’t know of any source that attempts to tease out the exact contribution of all of these things, but I would note that overdose deaths have risen the most in very conservative Midwestern states that haven’t walked back the drug war as much as California. Conclusion: As usual, I appreciate San Fransicko’s corrections to the prevailing narrative, but its own additions are dubious. Its claim that Portugal saw increased drug-related deaths seems false as far as I can tell. Its claim that it saw increased drug use depends on your definition, but is misleading and not the most natural way to sum up the evidence. Claim 6: San Francisco’s Soft-On-Crime Policies Led To Rising Crime Ten years ago, the news was full of stories about how some teenager stole a gumdrop and was sentenced to nine hundred billion years in jail. At some point, there was a genre shift to stories about how some hardened criminal murdered fifty people with an axe and the judge let him go with a warning because having jails felt racist. Source: Ed West, do note that this example is from the UK How suspicious should we be of each type of story? There will always be an extreme right tail of overly harsh sentences, and an extreme left tail of overly lenient ones. Were the 2000s really as draconian as they felt? Is the modern era really as pathetic? Or is it all just a function of who you read and what agenda they’re pushing? Shellenberger: During California governor Jerry Brown’s time in office, voters passed several reforms aimed at reducing the size of the prison population. In 2012, voters passed a change to the Three Strikes law so that the third strike imposes a life sentence only if the new felony was serious or violent. In addition to lowering punishments for drug possession, Proposition 47, which voters passed in 2014, redefined shoplifting, forgery, petty theft, and receiving stolen property as misdemeanors when the value in question does not exceed $950. In 2016, voters approved a proposition that shortened the time it took for some nonviolent offenders to be eligible for parole and which released nonviolent offenders into drug treatment and rehabilitation. Property crimes rose in San Francisco starting in 2012. Larceny, which is shoplifting and other petty theft, rose 50 percent, from roughly 3,000 incidents per 100,000 people in 2011 to about 4,500 in 2019. Property crimes as a whole, which include larceny, motor vehicle theft, and burglary, rose from 4,000 incidents per 100,000 people in 2011 to 5,500 in 2019. One study suggests that Proposition 47 increased the rate of auto theft 17 percent and the rate of larceny (non-auto property) theft 9 percent, but discerning between causation and correlation may not be possible. Upon taking office in January 2020, [famously soft-on-crime San Francisco district attorney Chesa] Boudin followed through on his campaign promises. Instead of prosecuting and incarcerating people for breaking car windows to steal money and other items from inside, Boudin proposed creating a $1.5 million fund to reimburse car owners. But there were over 25,000 car break-ins reported in 2019. If every break-in cost just $250 in repairs, the fund would need four times that amount. And what would prevent people from falsely claiming to have been robbed in order to get city money? […] Boudin opposed efforts by the mayor and the city attorney to prevent drug dealers who had already been arrested from entering the Tenderloin. “Until the city is serious about treating addiction and the root causes of drug use and selling,” said Boudin in a statement, “these recycled, punishment-focused approaches are unlikely to succeed at doing anything more than making headlines.” Home burglaries rose in early 2021 in San Francisco. Homeowners started posting on Twitter videos from their security cameras of people breaking into homes and garages. “When I first moved here we had a car break-in problem,” said Michael Solana, a writer who works for a venture capital fund. “Now we have a home invasion problem. These things are wearing on people.” Boudin attributed the rise of burglaries in San Francisco to the decline of tourism and “people in desperate economic circumstances.” Progressive supervisor Hillary Ronen agreed. “We know that [economic insecurity and inequality] is one of the root causes of property crimes specifically,” she said. But Tom Wolf and others argued that the robberies were, like the shoplifting, done by people seeking money to buy drugs and feed their addictions. “The drugstores have been shoplifted to death and that’s all because of drug use,” said Tom. “I know. I used to do the same thing when I was out there. That’s what you do. You ‘boost.’ And then you go and you sell your stuff down at UN Plaza,” an open-air drug scene. In a May 2021 city supervisors’ meeting, a representative from CVS called San Francisco “the epicenter of organized retail crime in the country” and claimed that 85 percent of the shoplifting is committed by organized theft rings. Police broke up one such ring in October 2020 and recovered $8 million of stolen merchandise. The problem goes beyond property crime. Boudin declined to prosecute two men who went on to kill people. One man had been repeatedly arrested for stealing cars, despite having just been released from prison earlier in the year, and appeared to be abusing meth. On New Year’s Eve, 2020, the man killed two people while driving intoxicated. Police found inside of his car a semiautomatic handgun and twenty-three grams of methamphetamine. On February 4, another intoxicated driver killed a pedestrian in a stolen car. The San Francisco police had arrested him in October 2020 for possessing a stolen car, a tool for stealing cars, and what appeared to be meth. Boudin chose not to pursue charges. In December, the California Highway Patrol arrested the man again for driving a stolen vehicle under the influence. Again he was not prosecuted. The accident victim, an immigrant from Kenya, and his wife had moved to San Francisco two weeks before the fatal crash. “I blame the DA,” said the widow of the victim. The suspect, she said, “was someone who was out in the public who shouldn’t have been in the public. It was completely avoidable.” Tom said he could feel the difference on the streets. “Drug dealing is unabated and it’s not one guy, it’s fifty guys dealing fentanyl and meth,” he said. “And it’s going unabated because the district attorney says, ‘These are the nonviolent, quality-of-life crimes,’ and ‘I’m not going to prosecute them.’” [..] District Attorney Boudin was offering weaker sentences than even defense attorneys were requesting, according to Vicki Westbrook of San Francisco. “There’s a defense attorney who said, ‘It used to be that I would argue for this deal in court with the DA but now I don’t say anything because the DA is going to offer me a deal better than what I would have suggested. Somebody shot up the street with an automatic weapon. The first offer was six months in jail or time served plus two years of probation or something. And then [the DA] said, “How about thirty days in jail?”’” Vicki laughed. “You really can do anything in San Francisco,” she said. “If you do get arrested, chances are you’re going to be out of jail in less than thirty days for damn near everything except maybe killing somebody and maybe even then, too. It’s hard to say at this point.” Taking each of these points individually: Proposition 47 There are two good big studies on the effects of Prop 47, one by Public Policy Institute and one by some UCI criminologists. The PPI study finds that the proposition increased theft and car break-ins by about 10%. The UCI study finds the same, but notes that under different assumptions the effects wouldn’t quite obtain statistical significance. This seems a bit too much like post hoc trying to get rid of an inconvenient effect, plus an effect on the border of statistical significance is different from positively finding no effect. I think a reasonable interpretation is that theft and car break-ins rose about 10% because of the proposition, just as Shellenberger says. Some pro-47 sites note that most states have some limit on how much you to have to shoplift before it’s a felony, and Prop 47 brought California closer to the national average, rather than turning it into an outlier. Chesa Boudin Chesa Boudin took office two months before the COVID pandemic began. Any attempt to separate the effect of Chesa Boudin from the effect of the pandemic is doomed. Shoplifting definitely plummeted when Boudin took office, but that’s because all the stores were closed. Murders definitely rose a little after Boudin took office, but that’s because that was also when the Black Lives Matter protests happened, which demoralized police and led to a so-far-permanent spike in murders nationwide. Percent of criminals caught definitely fell when Boudin took office, but that’s because various aspects of the justice system were closed for COVID (I will grudgingly entertain speculation that a further decrease in arrest rates from 2020 to 2021 may have been a genuine Boudin effect). In the absence of any real way to judge his performance, I think San Fransicko’s points about Boudin are plausible, though speculative. Shoplifting This one is terrible. There’s a surprisingly spirited debate here (some of you may have already read Applied Divinity Studies’ article). The debate is: everyone on the ground in San Francisco - store owners, security guards, customers, random citizens - say that shoplifting has increased massively over the past decade. But statistics mostly say it hasn’t. Source here. This is shoplifting crimes per 100,000 people. Kern County is a deep red county in California (including Bakersfield) that is known for being tough on crime. Against this, seriously, everyone says that shoplifting has obviously increased. I had a patient who worked in shoplifting prevention, he told me - his psychiatrist! Who he had no reason to lie to! - that he was constantly stressed dealing with the shoplifting surge devastating the stores he covered. Here’s the San Francisco subreddit’s response to someone posting the data showing shoplifting hasn’t risen - it’s just a lot of people laughing hysterically. What’s going on? I was able to find a different set of statistics that does seem to show a longer-term increase in shoplifting (source): The very big spike at the end might be a change in reporting by one or two stores - you can find the argument here. But it does look like shoplifting went from about 125 incidents/month in the early 2010s to more like 250/month just before the pandemic. Why is this graph so different from the other one? It looks like the top one came from the Department of Justice, and the bottom one came from SFPD. I’m not sure why these report differently. When you multiply out by 800K people in SF, by 12 months/year, and 30ish days/month, the first graph corresponds to 4 shoplifting incidents per day, and the second to 6. As LouB’s analysis here points out, that seems suspiciously low for a city of 800,000 people where stores are constantly closing because of shoplifting. Maybe off by a factor of a few hundred from what we’d expect. LouB writes: The SFPD report only references shoplifting offenses that required SFPD officers to prepare an incident report. That means either the shoplifter fought security, committed additional crimes, or stole more than $950 worth of items. It’s not that SFPD’s report is erroneous, it’s just not a representative statistic. In a parallel statistic, SFPD only completes incident reports for traffic accidents when there is an injury. Therefore, thousands of noninjury accidents are handled civilly without SFPD reports the same way thousands of shoplifting offenses are handled without reports. An insurance company would not determine premium rates based solely on SFPD incident reports, nor should readers interpret SFPD shoplifting reports as anywhere near the total picture of the shoplifting epidemic in San Francisco. (this would also explain why one or two stores changing their reporting policy can produce a spike equal to everyone else in San Francisco combined) But comparing incident reports from 2010 to incident reports from 2020 should still be apples-to-apples, unless the likelihood of reporting any given incident changed in the meantime. Did it? This news article quotes a San Franciscan who says that when they try to report shoplifting incidents, the cops tell them not to because “it doesn’t make a difference”. If cops say that now more often than they used to, it would make all these statistics meaningless. (Applied Divinity Studies claims to have an argument that shows this can’t be true. It goes something like: if San Francisco was a better place to shoplift than its neighbors - eg Oakland - then shoplifters would leave Oakland to go to San Francisco, and we would see Oakland shoplifting rates falling. Oakland shoplifting rates are falling, but no more so than the rest of the state, so there can’t be increased tolerance for shoplifting in San Francisco. I find this dubious for many reasons. First of all, many of the same reasons shoplifting is up in San Francisco - like Prop 47 or soft-on-crime progressive policies - also apply to Oakland. Second, given that shoplifting fell massively everywhere because of the pandemic, it feels dubious to try to compare different cities; maybe one city had stricter pandemic lockdowns than others. Third, do criminals really shop around for friendly jurisdictions? If so, why are so many crimes like car break-ins, concentrated in “the bad part of town”? Why wouldn’t criminals leave the bad part of town for under-exploited areas with richer residents and less competition? Maybe criminals in fact aren’t very strategic or mobile? Maybe they don’t want to stand in the BART station and then take a half-hour train ride holding a bag of stolen goods?) Maybe a better argument against this being true is how stable the shoplifting rates have been over time. Wouldn’t it be weird if (let’s say) a tripling of the real shoplifting rates was matched by a third-ing of the reporting rates (rather than a halving or a quartering or whatever)? On the other hand, here’s Shellenberger with some helpful data: Some of this is probably because of Proposition 47, which made some forms of shoplifting punishable with citation rather than arrest (but wouldn’t that be a clear discontinuity rather than a gradual trend?) But overall it sure seems like shoplifting is being taken less seriously, which might encourage people to report less. Another statistic I see is that only 2.3% of shoplifting cases result in an arrest; I don’t know how this is different from the graph above with numbers in the 30s; maybe it involves different levels of what makes something a “case”. I accept that the data don’t consistently show a spike in shoplifting. But what’s the alternative? My patient who works in loss prevention in SF stores is lying to me? The nice elderly Chinese man who sold me my last pair of glasses and chatted to me about the rampant shoplifting in his mall was lying? The San Francisco police are lying? Walgreens pretends to be concerned about shoplifting as part of a dastardly plot to close a bunch of stores for no reason? Target and CVS pretend to care about shoplifting as part of a plot to restrict their stores’ opening hours for no reason? Every big store near me has suddenly gotten a security guard at the front as part of some corporate-sponsored jobs program? Maybe the conservative narrative that soft-on-crime San Francisco must be experiencing rising crime rates took on a life of its own. Maybe it infiltrated not just the usual suspects like the SF police unions, but even such supposedly-liberal bastions as the New York Times. Maybe lots of big corporations took advantage of the fake narrative to make unpopular business decisions they were planning on making anyway. And maybe ordinary San Franciscans, confronted with everyone telling them they were in a shoplifting epidemic, started paying more attention to security guards and petty criminals who had always been there, a sort of mass hallucination that gripped everyone in the city. I can’t rule this out. Americans thought crime was rising all throughout the early 2000s, when it was in fact way down. Or maybe some statistics that we already know are off by several orders of magnitude got off by an additional factor of two or so. I think this one is more likely, but I’m genuinely not sure. Other Crime From the Economist: The Center on Juvenile And Criminal Justice puts it even more starkly, arguing that “San Francisco’s ‘Crime Wave’ Is Just One Crime”: This are potentially susceptible to the same reporting bias as shoplifting. So what about homicide? Homicide is practically always reported and investigated, making it a gold standard in crime measurement. (source) Looks pretty good until 2019. I don’t expect to gain useful information post-2020; the pandemic and the post-George-Floyd murder surge will make it impossible to evaluate for local variation. What about compared to other places? For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
All of this started when I wrote about California governor candidates. My post described Shellenberger as opposing suboxone treatment and supporting “sweeping institution” of the mentally ill. A commenter quickly pointed out that I was wrong about suboxone (Shellenberger supports it when appropriate), and I quickly corrected that. But Shellenberger said on Twitter I was also wrong about the institutionalization claim:
February 09, 2023 · Original source
In theory this also paves the way for human meat, though regulators might have other ideas. 2: Eight years ago I wrote an article about how the government should stop restricting doctors’ ability to prescribe suboxone, a useful medicine for opioid abuse. Last month, the government finally stopped the restrictions. Good for them! 3: Carl Sagan married three times. His first wife was legendary biologist Lynn Margulis, who discovered mitochondrial endosymbiosis, then went off the deep end and became an AIDS denialist and 9/11 truther. His second wife drew the Pioneer plaque. His third wife was one of the women who designed the Voyager golden record. 4: Claim: Chinese sources seem to back this up (and related BBC), but I’m skeptical: is this really the best way to satisfy a “must fight with medieval weapons” constraint? Why not crossbows? 5: Did you know: Alex Berenson, who runs the most popular anti-vaccine Substack, has had an unusual career: he used to be an investigative reporter for the New York Times, and also wrote a series of bestselling spy novels. 6: Less Wrong: I Converted Book 1 Of The Less Wrong Sequences Into A Zoomer-Readable Format. Apparently there’s a thing where Zoomers are supposedly more likely to learn a text if you overlay it on on a fast-paced video game, example here. 7: By this point we’ve probably all heard stories about people who win the lottery and then end up bankrupt and miserable after X months or years. I had always assumed this was limited to very poor people with no understanding of money. This forum post argues it’s not, and tells the story of a man who started out with $15 million and still ruined his life after winning $170 million more in the lottery. 8: Did you know: Exiliarch Mar-Zutra II was a 5th century Jewish leader who took advantage of the chaos caused by weird Zoroastrian communists to secede and turn the city of Al-Mada’in, Iraq into an independent Jewish state for seven years. 9: Why doesn’t the Supreme Court have vice-justices? 10: Steve Sailer (warning: unz.com, far-right site, some firewalls will flag or block it): why aren’t there more gay English soccer players? Thousands of current or recent English pro soccer players, the media is really interested in finding a gay one so they can run a “Historic First” article, and apparently they can’t. There are rumors that players are afraid to come out because of homophobia, but there are at least 2,000 retired soccer players and only one of them has come out as gay. “I’m increasingly sympathetic to [the] theory that whatever psychosocial traits make men highly interested in team sports make them highly heterosexual too”. Is this true of other countries and other sports? 11: Adam Tooze on the demographic background to Iran’s protests. Iran thought it was facing an overpopulation crisis in the 80s and tried some reforms to lower family size. The reforms worked overwhelmingly well, causing “the most dramatic transition ever recorded in demographic history”, from 6.5 to 2.5 children per woman in thirty years. Iran now has “lower maternal mortality than the US”, and an education system where “women in university outnumber males”. This kind of demography isn’t usually compatible with patriarchal religious institutions, and the Ayatollahs are aware of this; in a rare admission of error, Khameini said that “Government officials were wrong on this matter, and I, too, had a part. . . . May God and history forgive us.” Now they’re trying to increase average family size and put the genie back in the bottle; Hungary can tell them about the limits of that strategy. 12: What it looks like to be on shrooms: I haven’t used shrooms myself so cannot confirm or deny, but this is oddly compelling, and makes some things I’ve read about neuroscience of vision make more sense. I wonder if you could get HPPD from watching videos like this for too long. 13: Study: federal cancer funding is extraordinarily effective. Cancer research produces so many valuable treatments that it saves one DALY per $326 spent. For comparison, health systems usually consider an intervention good value-for-money if it saves at least one DALY per $50,000. By combing the Earth far and wide, effective altruists have tentatively found one or two opportunities in the poorest parts of Africa to save lives at $100/DALY, but these are extremely rare exceptions and I wouldn’t have expected anything in the US to be within an order of magnitude of that. Either this finding is fake, or we should all be donating to federal cancer research instead of whatever else we’re doing. 14: Yet another person building a vast theory of human interaction off of the characters in The Office. This one is pretty good, also name-drops Bobos In Paradise. I’m still surprised this is such a common thing. 15: Marginal Revolution: FDA Deregulation Increases Safety And Innovation And Reduces Prices. Study looks at what happens when the FDA reclassifies medical devices from a highly-regulated to a less-highly-regulated category; in general, those devices get better, cheaper, and there are somewhere between similar and fewer deaths/injuries related to those devices. Why would safety increase? The author suggests that regulation is a defense against lawsuits (“Your Honor, the FDA agreed to approve our device, so it can’t have been bad!”), and removing that defense makes companies more lawsuit-conscious and careful; Alex Tabarrok suggests a bigger effect may be allowing more innovation towards safer versions. 16: Ozy writes about Interesting People Of History: Charles Williams (ie the other member of the Inklings) 17: Did you know: the Congressman who founded the House Committee On Un-American Activities was, in fact, a paid Soviet spy (tweet, Wiki article). This actually makes sense; he originally started HUAC to root out fascists, and it only got turned against communists later on. “There has been a push to rename the street [currently named after the Soviet spy], but as of 2018 it has been unsuccessful.” 18: Idle Words: Why Not Mars? Surprisingly strong argument for why sending humans to Mars is harder than people think, of minimal scientific value, and likely to contaminate all future searches for microbial life and ruin our chance to study the topic. Concludes that we should abandon the allure of human space travel and just send probes everywhere. This makes short-term sense, but I wonder what this author’s vision of the future is - do we just stay on Earth forever? If not, don’t we have to start trying to do the hard thing at some point? (I don’t care about this because I assume AI will will flip the gameboard one way or another, but Ceglowski is a noted singularity skeptic and should probably have opinions about long-term things). 19: Metacelsus and Razib on epigenetics. Stop using it to claim there’s “intergenerational trauma”! 20: Tafl games are a family of European games, played in areas as diverse as Iceland, Ireland, Britain, and Denmark, probably sharing descent from a now-lost board game of ancient Rome. One of them, Hnetafl, was the chief board game of the Vikings and is affectionately called “Viking chess”. The one we actually know the rules for is the Saami version, Tablut, which survived long enough for Linnaeus (the taxonomy guy!) to write down the rules. 21: Shot: Chaser: (source) 22: Related: the very center of GPT’s embedding space contains a few unusual tokens including the string “SolidGoldMagikarp”. GPT displays anomalous behavior if these tokens are inserted in a query; for example, it treats “SolidGoldMagikarp” as the word “distribute”. ChatGPT is pretty advanced and fails semi-gracefully here; GPT-2’s reaction to these tokens is more disturbing: (source: Less Wrong) Further investigation determined that many of these tokens are the screen names of a group of Redditors who attempted to count to infinity. The most likely explanation, according to the discoverers, is that these names were in GPT’s tokenization data, but not its training data (maybe they were especially common in the tokenization data because they made thousands of posts with numbers in them, but didn’t make it into the training data because their posts had no content?) - that leaves them existing without content, and GPT tries to round them off to some other “nearby” token (by incomprehensible AI standards of nearbyness). Congrats to the SERI-MATS AI alignment researchers who found all of this; maybe this makes it 0.0001% less likely that the AI which controls the nuclear arsenal in twenty years will have equally inexplicable behavior. 23: More language model news: LLM that understands and can explain images
Toyota

Toyota is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between March 25, 2021 and April 05, 2023. The archive places it in contexts such as "If both Ford and Toyota ban blacks at the same time"; "all of the giant world-spanning Toyota-style companies you get in the next round of development"; "There's no way you'll be able to outcompete Ford, Toyota, and Tesla". It most often appears alongside Tesla, America, Bill Gates.

Article page
Toyota
Mention count
3
Issue count
3
First seen
March 25, 2021
Last seen
April 05, 2023
March 25, 2021 · Original source
Diversity libertarianism is usually in favor of companies being allowed to do a wide range of things, because it ensures everyone will be well-served. If you assume an arbitrarily large number of uncorrelated companies, then whatever the thing you want is, there's at least one existing or easy-to-start company doing it. If Ford refuses to sell cars to black people, Toyota should see a profit opportunity and step in. If both Ford and Toyota ban blacks at the same time, some upstart like Tesla should step in. If Ford, Toyota, and Tesla all do it, some guy with a wrench who's always dreamed of making cars in his garage should notice a billion-dollar business opportunity lying on the ground, get seed capital from equally greedy investors, and solve the problem.
June 28, 2021 · Original source
But even beyond this, Studwell talks up the almost spiritual benefits of land reform. In a typical land reform measure, an equal amount of land gets allotted to every peasant family. This is about as close as anything ever comes to the completely fair starting position that eg John Locke liked to fantasize about. Everyone gets to work for themselves in their own little small business, reaping the consequences of their own decisions. The generation who grow up immediately after a land reform tend to be thrifty, hard-working, honest, and civic-minded. They go on to found all of the giant world-spanning Toyota-style companies you get in the next round of development. Maybe this is just a coincidence; most people are farmers, and most farmers are affected by land reform, and the land-reform stage of the development pathway is separated by the found-giant-companies stage by about a generation. But Studwell thinks it's more than this, and maybe it's more than a coincidence that Asia and America have come to fetishize the virtues of small farmers in pretty much the same way.
Imagine having to start your own car company in Zimbabwe. Your past experience is "peasant farmer". You have no idea how to make cars. The local financial system can muster up only a few million dollars in seed funding, and the local manufacturing expertise is limited to a handful of engineers who have just returned from foreign universities. Maybe if you're very lucky you can eventually succeed at making cars that run at all. But there's no way you'll be able to outcompete Ford, Toyota, and Tesla. All these companies have billions of dollars and some of the smartest people in the world working for them, plus decades of practice and lots of proprietary technology. Your cars will inevitably be worse and more expensive than theirs. Every country that's solved this problem and started a local car industry has done so by putting high tariffs on foreign cars. Locals will have to buy your cars, so even if you're not exactly making a profit after a few years, at least you're not completely useless either.
April 05, 2023 · Original source
Who “won” the automobile race? Karl Benz? Henry Ford? There were many steps between the first halting prototype and widespread adoption. Benz and Ford both personally got rich, their companies remain influential today, and Mannheim and Detroit remain important auto manufacturing hubs. But other companies like Toyota and Tesla are equally important, the overall balance of power didn’t change, and today all developed countries have automobiles.
Twitter Blue

Twitter Blue is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between February 02, 2023 and September 18, 2023. The archive places it in contexts such as "sites could verify through payment - something like Twitter Blue"; "Twitter Blue was a dud"; "Twitter Blue was a dud, anecdotally I’ve been seeing lots more people using it lately". It most often appears alongside Twitter, Ashlee Vance, Boeing.

Article page
Twitter Blue
Mention count
3
Issue count
3
First seen
February 02, 2023
Last seen
September 18, 2023
February 02, 2023 · Original source
If nothing else works, sites could verify through payment - something like Twitter Blue. Propagandabot owners could pay for one account, but not separate accounts for each of the thousands of people they want to reach. And if one account started messaging thousands of people, this would be suspicious activity that moderators could detect and remove.
September 13, 2023 · Original source
Although stories from this winter claimed that Twitter Blue was a dud, anecdotally I’ve been seeing lots more people using it lately. This could provide X with a revenue source independent of advertising and make them well-placed to survive any future chatbotpocalypse.
September 18, 2023 · Original source
>> “Although stories from this winter claimed that Twitter Blue was a dud, anecdotally I’ve been seeing lots more people using it lately. This could provide X with a revenue source independent of advertising and make them well-placed to survive any future chatbotpocalypse.”
As for this I am fairly certain that's just Scotts twitter bubble. Twitter blue is still relentlessly mocked across much of twitter. An amount of accounts that find value in the benefits for outreach for content/business/whatever do exist - reluctant or otherwise. But that's not a significant enough demographic to rely on at its current cost. And the benefits it offers do not warrant higher pricing. For the average user blue still just is not appealing. For the most part it's relegated to the afformentioned accounts that highly value the benefits, or Musk fanboys/tech adjacent enough accounts. Which is fine, but feeds back into the central conceit of this whole micro-discussion: Musks successes can outperform Musks failures. The pipeline from his PR ability to twitter blue sales and thus an alternate revenue stream is so direct it feels like a contrived hypothetical built almost exactly to explore this topic.
The twitter bubble you inhabit definitely makes a big difference to your perception here! The vast majority of users in my niche of twitter have left, nobody has twitter blue; the site is just a fairly boring wasteland for me now, punctuated with the odd promoted Elon tweet which I have no interest in. I went from a decent amount of daily use to only checking it once or twice a week.
Vyvanse

Vyvanse is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between January 25, 2021 and November 30, 2022. The archive places it in contexts such as "Vyvanse is the newest and most expensive member of the amphetamine stimulant family"; "Almost everyone likes Vyvanse better than what they were taking before"; "I will try Vyvanse (or some other solution to stimulant “crashes” )". It most often appears alongside Dexedrine, FDA, Adam.

Article page
Vyvanse
Mention count
3
Issue count
3
First seen
January 25, 2021
Last seen
November 30, 2022
January 25, 2021 · Original source
Vyvanse is the newest and most expensive member of the amphetamine stimulant family. It's lisdexamphetamine - ie Dexedrine attached to a random inactive molecule called lysine. As long as the lysine is attached, it can't stimulate anything. The body removes the lysine at a slow, consistent rate, which means that you get a slow, consistent release of stimulant into the bloodstream. This is advertised as especially good for people who are worried about addiction. It's hard to abuse or overdose on Vyvanse; no matter how much you take, your body will still only activate it at the same, slow rate.
My patients love Vyvanse. I try hard to convince people to take older, less expensive medications unless they're absolutely sure that the newer flashier one works better, but my patients are very convinced Vyvanse works better than Adderall. I used to think this was because something about the complicated timed release mechanism makes it "smoother". This is definitely what the pharma company that designed it wants me to think, and I admit there is some evidence for it.
But one neglected perspective is that once you take away the lysine, Vyvanse is basically Dexedrine, not Adderall. Almost everyone likes Vyvanse better than what they were taking before. But usually they were taking Adderall before. If Dexedrine is really better than Adderall - and common sense and the patient rating websites say it is - then that goes some of the way to explaining Vyvanse's superiority before we even get to the complicated timed release stuff. Pharmaceutical companies are always trying to re-release old medications in ways that bamboozle you into thinking they're new medications, so they can charge more money for them. In this case they did so good a job that I honestly can't tell if that's what they're doing or not.
January 31, 2021 · Original source
1. Thanks to everyone who commented on the amphetamines thread. The main things I learned: another way of thinking about the difference between racemic, d-, and meth- amphetamine is the ratio of central to peripheral effects. One major reason druggies prefer methamphetamine to unsubstituted is because it’s easier to make. I was wrong about Vyvanse; it gets cleaved by red blood cells, not the liver. And one reader links me to this conspiracy theory (sorry, it’s actually very reasonable, I just can’t help thinking of it that way) that Vyvanse doesn’t have superior pharmacokinetics to other amphetamines at all, and it’s all just Dexedrine + hype; I haven’t had enough time to examine the theory in depth but am interested in people’s thoughts.
November 30, 2022 · Original source
Doses needed for consistent weight loss/maintenance are much higher than for, say, ADHD. Plus every time the damned things wear off, ALL the hunger arrives at once. And you have to let them wear off, because otherwise sleep is terrible. (I was prescribed Dexedrine for weight loss several decades ago by a crazy doctor, and am now on a decently high dose of Vyvanse for ADHD).
Wal-Mart

Wal-Mart is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 04, 2021 and November 08, 2021. The archive places it in contexts such as "If this really happened then Wal-Mart would be put out of business"; "Wal-Mart would be put out of business"; "the obese white Boomer who shops at Wal-Mart". It most often appears alongside America, "How do you do, fellow kids?", #NotAllMen.

Article page
Wal-Mart
Mention count
3
Issue count
3
First seen
May 04, 2021
Last seen
November 08, 2021
May 04, 2021 · Original source
The imbalances seem not to trouble the Bush administration, judging by cavalier statements to the effect that the current account deficit, if it is a problem, can easily be dealt with by people buying US-made goods (as if such goods are readily available and cheap enough and as if nominally US-made goods do not have a high foreign-input component). If this really happened then Wal-Mart would be put out of business. The budget deficit, Bush says, can easily be dealt with without raising taxes by curbing domestic programmes (as if there are any large discretionary programmes left to dismantle). Vice-President Cheney’s remark that ‘Reagan taught us that budget deficits do not matter’ is alarming, because what Reagan also taught is that running up deficits is a way to force retrenchment in public expenditures and that attacking the standard of living of the mass of the population while feathering the nests of the rich can best be accomplished in the midst of financial turmoil and crisis. If, furthermore, we ask the general question, ‘Who has actually benefited from the numerous financial crises that have cascaded from one country to another in wave after wave of catastrophic deflations, inflations, capital flights and structural adjustments since the late 1970s?’, the weak commitment of the current US administration to fending off a fiscal crisis in spite of all the warning signs becomes more readily understandable. In the wake of a financial crash, the ruling elite may hope to emerge even more empowered than before.
May 10, 2021 · Original source
In 2014, armed with this model, I predicted that hip young people would go far-right. For the previous few years, the social justice movement had been the dominant intellectual paradigm in online spaces (and increasingly offline too). The movement had started with the same people who start all trends - starving bohemian artists, poor people on the fringes of society, hip college kids. Beginning around 2008 it spread like wildfire among all the most popular and clued-in people I knew - all my favorite slightly contrarian bloggers, all the most interesting people at my college. But by 2014, it was starting to get embarrassing. We'd already seen the beginnings of "woke capitalism", where Wal-Mart or Amazon or whoever would put their corporate logos in rainbow colors for gay pride day and then everyone would praise them and talk about how they were striking a bold blow against the entrenched forces of the kyriarchy. Hillary Clinton, 25-year-contender for America's least cool person, was giving speeches about male privilege and rape culture. The Instagram pages of the hippest, most counterculture people in the country sounded exactly the same as the lectures corporate consultants gave at mandatory educational workshops. According to Bell's theory there was no way this was a stable situation.
And so I predicted that hip young people would go far-right. Nobody would confuse them with the maximally-uncool people, the obese white Boomer who shops at Wal-Mart and plasters their car with anti-Obama bumper stickers. And it would distinguish them from the corporate consulants and Hillary Clintons of the world. A few hip young people seem to have tried this - I think this was a little bit of what gave the alt-right its original appeal, especially after Clinton's speech.
November 08, 2021 · Original source
Marc Lore founded diapers.com and various other internet startups, served a stint as Wal-Mart’s e-commerce director, and made a few billion dollars. Now he wants to start a city in the deserts of the American West, with a new vision of socially responsible democracy.
Walmart

Walmart is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 30, 2021 and December 31, 2025. The archive places it in contexts such as "a Walmart catalogue"; ""woke capitalism", where Wal-Mart or Amazon or whoever would put their corporate logos in rainbow colors"; "companies have done a better job making Zoomers feel like expensive products are part of the good life (e.g. shopping at Walmart vs. Whole Foods)". It most often appears alongside 4chan, Chapo Trap House, CIA.

Article page
Walmart
Mention count
3
Issue count
3
First seen
April 30, 2021
Last seen
December 31, 2025
April 30, 2021 · Original source
Even though it’s possible to make educated guesses about how much a certain publication might be valuable to future historians – e. g. Barack Obama’s memoirs are more important that a Walmart catalogue – it’s very hard to predict what will be used by a future researcher and what won’t. The best guess is simply that anything might be valuable at some point. During the last two centuries, historians have broadened their interest from an almost exclusive focus on political and military history to things like social and economic history or the history of women and people of color. To a historian in 1850, information about the historical prices of bread, the use of cutlery, or the travel speeds of different kinds of merchant vessels might seem like footnotes to real history at best. A century later, Fernand Braudel used nothing but information of this sort to weave together a groundbreaking new history of medieval and early modern Europe. It is reasonable to assume that 21st- and 22nd-century historians will keep expanding their field in similar ways.
May 10, 2021 · Original source
In 2014, armed with this model, I predicted that hip young people would go far-right. For the previous few years, the social justice movement had been the dominant intellectual paradigm in online spaces (and increasingly offline too). The movement had started with the same people who start all trends - starving bohemian artists, poor people on the fringes of society, hip college kids. Beginning around 2008 it spread like wildfire among all the most popular and clued-in people I knew - all my favorite slightly contrarian bloggers, all the most interesting people at my college. But by 2014, it was starting to get embarrassing. We'd already seen the beginnings of "woke capitalism", where Wal-Mart or Amazon or whoever would put their corporate logos in rainbow colors for gay pride day and then everyone would praise them and talk about how they were striking a bold blow against the entrenched forces of the kyriarchy. Hillary Clinton, 25-year-contender for America's least cool person, was giving speeches about male privilege and rape culture. The Instagram pages of the hippest, most counterculture people in the country sounded exactly the same as the lectures corporate consultants gave at mandatory educational workshops. According to Bell's theory there was no way this was a stable situation.
And so I predicted that hip young people would go far-right. Nobody would confuse them with the maximally-uncool people, the obese white Boomer who shops at Wal-Mart and plasters their car with anti-Obama bumper stickers. And it would distinguish them from the corporate consulants and Hillary Clintons of the world. A few hip young people seem to have tried this - I think this was a little bit of what gave the alt-right its original appeal, especially after Clinton's speech.
December 31, 2025 · Original source
Cue commenters yelling at him for feeling like he “needs” to shop at a nice grocery store, and him very reasonably responding that the question asked about “feeling financially successful”, not about what he “needs”. So one interpretation of this question is that companies have done a better job making Zoomers feel like expensive products are part of the good life (e.g. shopping at Walmart vs. Whole Foods). I endorse this: I’m in the same social class as my parents, but I remember them shopping at the same grocery store as the poor people in their hometown, whereas I mostly shop at upscale hippiesh places.
Zembrin

Zembrin is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between April 28, 2021 and May 17, 2022. The archive places it in contexts such as "Zembrin, a concentrated extract of kanna advertised for low mood and anxiety"; "I wrote up a short page about Zembrin on my professional website"; "Less-well-studed but promising supplements including Zembrin and polygala tenuifolia". It most often appears alongside kanna, Lorien Psychiatry, SAMe.

Article page
Zembrin
Mention count
3
Issue count
3
First seen
April 28, 2021
Last seen
May 17, 2022
April 28, 2021 · Original source
Zembrin Is Interesting
But I and many other people have had good results with Zembrin, a concentrated extract of kanna advertised for low mood and anxiety. So I asked respondents to specify whether their kanna was Zembrin or something else. Of 37 kanna users, 20 used Zembrin and 17 used something else. The subgroup who used Zembrin reported a mean effectiveness of 6.88, which beats out modafinil to make it highest on the list. After ad hoc Bayesian adjustment, it was 6.72, second only to modafinil as the second most effective nootropic on the list. This really excites me - I've felt like Zembrin was special for a while, and this is the only case of a newer nootropic on the survey beating the mainstays. And it's a really unexpected victory. The top eight substances in the list are all either stimulants, addictive, illegal in the US, or all three. Zembrin is none of those, and it beats them all.
Based on these preliminary results, I wrote up a short page about Zembrin on my professional website, Lorien Psychiatry, and I asked anyone who planned to try it to preregister with me so I could ask them how it worked later. 29 people preregistered, of whom I was able to follow up with and get data from 22 after a few months. Of those 22, 16 (73%) said it seemed to help, 3 (14%) said it didn't help, and another 3 (14%) couldn't tell because they had to stop taking it due to side effects (two headaches, one case of "psychedelic closed-eye visuals"). Only 13 of the 22 people were willing to give it a score from 1-10 (people hate giving 1-10 scores!), and those averaged 5.9 (6.3 if we don't count people who stopped it immediately due to side effects). That's a little lower than on the survey, but this was a different population - for example, many of them in their answers specifically compared it to prescription antidepressants they'd taken, whereas the survey-takers were comparing it to nootropics. Although these findings are not very useful without a placebo control, they confirm that most people who take Zembrin at least subjectively find it helpful.
May 25, 2021 · Original source
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
Zembrin is an extract of kanna, a South African plant. It appears to be an SSRI, but also to have other less-well-understood antidepressant properties that make it work a little faster. It has not been rigorously tested in studies, but has been helpful to me and several people I know. You can read more about it at its Lorien page.
Secretly I suspect Zembrin probably works better than 5-HTP or St. John’s Wort, but there’s not enough evidence for me to recommend it in good conscience.
May 17, 2022 · Original source
Finally, in my survey, I got impressive results for Zembrin, a certain extract of the kanna plant. This survey fails to replicate that - Zembrin lands exactly where the “how hard is it to get? how fancy is it?” model would predict, which is not very high. I’m not sure why my survey got such strong results. I know I was personally excited about Zembrin, so there’s room for experimenter bias, but I can’t think of how I would have added in the experimenter bias when I was just collecting your ratings. Maybe I bungled the statistics somehow? In any case, it’s a completely average anxiolytic in every way.
Zulresso

Zulresso is a recurring brand in the Astral Codex Ten archive, appearing 3 times across 3 issues between March 08, 2022 and March 16, 2022. The archive places it in contexts such as "Zulresso is the brand name of allopregnanolone (aka brexanolone), a new medication for post-partum depression"; "What studies were done on Zulresso? This followup study by Kanes was the first real RCT"; "the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!)". It most often appears alongside allopregnanolone, progesterone, FDA.

Article page
Zulresso
Mention count
3
Issue count
3
First seen
March 08, 2022
Last seen
March 16, 2022
March 08, 2022 · Original source
Wikipedia describes Zulresso as “A bat-winged, armless toad with tentacles instead of a face... ” - no! sorry! That’s Zvilpogghua, one of the Great Old Ones from the Lovecraft mythos.
Zulresso is the brand name of allopregnanolone (aka brexanolone), a new medication for post-partum depression. It’s interesting as a potential missing link between hormones and normal mood regulation.
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator!
March 10, 2022 · Original source
Earlier this week we talked about Zulresso, a new medication for post-partum depression. It works well, but it can only be administered at a few special hospitals, and costs $35,000 per treatment.
But Zulresso is a natural metabolite of the female hormone progesterone. What’s stopping people from taking progesterone, waiting for their bodies to metabolize it into Zulresso, and saving $35,000 and a hospital stay?
Andreen et al give some people a dose of 20 mg progesterone, then measure allopregnanolone levels. They find that the progesterone gets converted into allopregnanolone, with a max plasma concentration of about 8 nmol/L. This is about a fifth of allopregnanolone levels during pregnancy, which a course of Zulresso is trying to match. So in theory (and assuming simple pharmacokinetics) a dose of 100 mg progesterone ought to give the same peak level of allopregnanolone as a Zulresso infusion.
March 16, 2022 · Original source
Thanks to everyone who commented on Zounds! It’s Zulresso and Zuranolone and on the followup Progesterone Megadoses Might Be A Cheap Zulresso Substitute. I’m constantly impressed by the expertise of commenters here and on how much better the biomedical comment threads are compared to some of the others. Among the things I learned:
— Metacelsus (who writes the blog De Novo) doubts the price estimates I posted:
— Douglas (who writes the blog A Mindful Monkey) clears up some mechanism details I missed:
Abercrombie & Fitch

Abercrombie & Fitch is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 16, 2022 and December 04, 2024. The archive places it in contexts such as "Brand loyalty becomes a way to signal that you’re the kind of kid who buys their clothes at Abercrombie & Fitch"; "their Abercrombie & Fitch white safari blouses and tan gabardine jodhpurs". It most often appears alongside Coke, 3D printing, AI.

Mention count
2
Issue count
2
First seen
February 16, 2022
Last seen
December 04, 2024
February 16, 2022 · Original source
...more than this. It’s an obsession with what kind of person you are. Brand loyalty becomes a way to signal that you’re the kind of kid who buys their clothes at Hot Topic/Abercrombie & Fitch, not at Abercrombie & Fitch / Hot Topic. It’s not that one of these stores is more prestigious (= signals class) better than the other. It’s that they signal what makes...
...ssion with what kind of person you are. Brand loyalty becomes a way to signal that you’re the kind of kid who buys their clothes at Hot Topic/Abercrombie & Fitch, not at Abercrombie & Fitch / Hot Topic. It’s not that one of these stores is more prestigious (= signals class) better than the other. It’s that they signal what makes you, you. If you shopped jus...
December 04, 2024 · Original source
...was like a certain stock scene from the jungle movies of that period. Bruce Cabot and Myrna Loy make a crash landing in the jungle and crawl out of the wreckage in their Abercrombie & Fitch white safari blouses and tan gabardine jodhpurs and stagger into a clearing. They are surrounded by savages with bones through their noses - who immediately bow down and...
...reres was like a certain stock scene from the jungle movies of that period. Bruce Cabot and Myrna Loy make a crash landing in the jungle and crawl out of the wreckage in their Abercrombie & Fitch white safari blouses and tan gabardine jodhpurs and stagger into a clearing. They are surrounded by savages with bones through their noses - who immediately bow down and prostrate themselves and commence a strange moa...
Adobe Illustrator

Adobe Illustrator is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 29, 2022 and January 11, 2023. The archive places it in contexts such as "image editing program Adobe Illustrator"; "Adobe Illustrator artifacts and weird white borders"; "weird artifacts showed up on Adobe Illustrator". It most often appears alongside COVID, Infowars, InfoWars.

Article page
Adobe Illustrator
Mention count
2
Issue count
2
First seen
December 29, 2022
Last seen
January 11, 2023
December 29, 2022 · Original source
Upon first inspection, the document appears to be a photocopy taken from state records and printed on official green paper. However, when the government released PDF is taken into the image editing program Adobe Illustrator, we discover a number of separate elements that reveal the document is not a single scan on paper, as one might surmise. Elements are placed in layers or editing boxes over the scan and green textured paper, which is to say the least unusual.
Snopes investigates and contacts an Adobe Illustrator expert who says that this is true. Illustrator does show the PDF as containing several different layers and elements, but that’s because Illustrator tries to “guess” at what items in a document should be grouped together to make it easier for users to edit, and sometimes it gets it wrong.
The Infowars people are conspiracy theorists, so they think Adobe Illustrator artifacts and weird white borders are enough evidence to point to a plot. I think they’re dumb and paranoid. But they’re not lying! They’re noticing weird things that are really there - things so minor that no non-paranoid person would care about them - and writing articles highlighting these true things instead of the many other true things that would help you understand that this is a boring non-story.
January 11, 2023 · Original source
Did anyone in your family (as per your best guess) die of COVID vaccine side effects? I got 917 responses so far. On Kirsch’s original poll, the answers were 3.5% and 7.9%; on my survey, they were 6.8% and 0.9%. I think my higher rate of COVID deaths was because I carelessly changed “household” to “family”, which includes eg extended family. But why did I get so many fewer vaccine deaths? Looking at these people's other responses, they did not show a consistent tendencies to make things up or say outrageous things (except for one who listed their religion as “Satanist”). That having been said, they did have an atypical response pattern; most ACX readers are white male Westerners, but these people were 38% female, 38% nonwhite, and 88% non-American. Highest degree was 12% high school, 25% college grad, and 63% postgrad; IQs were listed as extremely high, just like everyone else who gives their IQs on my survey. Politics were significant for 25% Marxist (otherwise a rarity in my survey), but otherwise typical, and did not lean right-wing. They were slightly, but not overwhelmingly, more likely to distrust the media and dislike strong COVID responses than other survey respondents. Overall I don't feel like I learned too much from examining them. The survey is still open (take it now if you haven’t already!) and I'm hoping to get more data on this later. 5: Comments Pointing Out Very Clear Examples Of Media Lies Several people agreed with the wider point, but tried to find a counterexample - a media lie so explicit that nobody could ever deny it. Some people noted that the term “fake news”, when invented in 2016, was originally applied to a very specific kind of fake article, often from weird Macedonian article mills, that were saying utterly fake stuff in a way that even Infowars didn’t. Robert Stadler: This was what was interesting about the phenomenon of "fake news" during the 2016 election, before that term was successfully hijacked by Donald Trump to mean "news stories I don't like." There was a wave of what looked like news articles, spread largely via Facebook, that were entirely fictitious. The people writing those "articles" were not journalists and were not trying to be journalists. They made up the stories out of a mix of rumor and complete fabrications, either for political purposes or just as click-bait (this has never been entirely clear to me). It's unfortunate that the term "fake news" has been so thoroughly tainted, because the existence of those articles was genuinely noteworthy, and it's now harder to talk about them . . . I don't remember any myself (since it's been 6 years), but here's a study which has some specifics - http://web.stanford.edu/~gentzkow/research/fakenews.pdf After some searching, Benjamin Jest (writes As Fair A Name) was finally able to produce a specific example - Nancy Pelosi Hanged At Gitmo - which does, indeed, claim that leading US Democrat Nancy Pelosi was hanged at Guantanamo Bay for “treason and conspiracy” on December 27, 2022. It seems to suggest that the order was given by Donald Trump, who is still President, and that Hillary Clinton had already been executed in the same manner in April 2021. I will admit this is definitely an example of a “news source” making things up rather than just stretching the truth. The source, RealRawNews, claims on its About Page to be a “parody site”, but this outside article about them says they go back and forth between claiming to be a parody and claiming to be real. Some of their claims are more plausible than the Gitmo one - for example, that many Air Force pilots were resigning because of the COVID vaccine mandate - but equally false. They seem to go back and forth between “things that some conservatives might believe to be true” and “things that are obviously false but maybe gratify conservatives’ id”, adding or subtracting the “parody” label based on which one they’re doing at the time. It’s a fascinating business model, and I guess the term “fake news” fairly applies to it. Yug Gnirob writes: I don't know how to find them, but I definitely remember several completely fake articles about Trump during and immediately after the election. One of them was him citing "an ancient law" that prevented President Obama from doing... some liberal thing, I don't remember what. The most memorable one was immediately after the "Muslim Ban", where they claimed it had resulted in the arrest of a high-priority terrorist on day 1. I feel like that one showed up on one of the fact check sites, but I'm not seeing it on Snopes. I remember Stephen Colbert reporting the articles had been tracked down to a couple of Macedonian teens, who had discovered that writing fabricated pro-Trump articles was an easy way to make money. 6: Comments Making Other Claims Of Media Lies And Misdeeds — Beowulf888 on the LA Times and COVID: Well, there are media outlets that propagandize—but I think it boils down to if it bleeds it leads. Most corporate media outlets have the economic incentive to increase the readership by grabbing one's attention with scary headlines and articles. The perfect example of this phenomenon was in April 2020 when the LA Times interviewed an atmospheric chemist at Scripps. She made the claim that SARS2 virus particles in sewage were being carried back to land by sea spray. The reporters and editors uncritically relayed her comments as if she were an expert with the same credentialled expertise as a virologist or epidemiologist. There are numerous reasons why this would be very very low on the threat level even with what little we knew about the SARS2 virus at that time. This story was picked up by the media everywhere, and county health officials (either because there was public pressure to do so, or because they really believed her) shut down beaches up and down the coast of California. Did the LA Times and the news media really have any motivation to promote the closure of public beaches? I can't imagine they did. But they did have a scary headline that would promote readership and spread LA Times as a news source. Some weeks later the LA Times did a retraction, but by that time it had entered the popular imagination that beaches were a potential vector for COVID infection. I’m developing an allergy to the word “uncritically”. Being able to fact-check scientists is a rare skill - I’m not surprised nobody at the LA Times had it ready to deploy for this exact article. — Mike Mulligan writes: The pushback is largely because you are doing a false equivocation between the New York Times (who you hate and have a vendetta against) and Infowars (who you are pretending does basically the same thing as other outlets). And you know this, but on your own metric it won't count as a lie, because you just selectively misrepresented things. On the two articles in this series, I’ve included phrases like “This doesn’t mean these establishment papers are exactly as bad as Infowars; just that when they do err, it’s by committing a more venial version of the same sin Infowars commits” and “Again, my goal here isn’t to . . . say NYT is exactly as bad as Infowars” and tried to explain the exact way that two things can both commit a similar error without one being exactly as the other (Hitler and someone who shot a robber in self-defense both committed a similar action called “killing people”, but this doesn’t mean they both killed exactly the same people with exactly the same level of justification). Still, I got numerous comments getting angry at me for saying that I was calling NYT exactly as bad as Infowars, and saying I was being deceptive / lying because of this. This is why I’m so convinced people are erring on the side of too mistrustful - you can fill your articles with sentences about how you’re not claiming X, and people will still find ways to accuse you of lying because you said X. — Garrett writes: [The way Infowars covered Obama’s birth certificate] isn't any different from eg. mainstream media coverage of anything which involves firearms. They make (or promulgate) so many stupid technical errors I've stopped paying attention to them at all. They could have 1 person on staff who's responsibility is to understand firearms and run everything past them. But they don't. To what should I attribute this continual stream of errors? Is mainstream media coverage of firearms honestly flawed? Is it “reckless disregard for truth?” Is it a “lie of egregious sloppiness?” I think your answer to this question will depend more on how bad you want to accuse the mainstream media of being, relative to other forms of media, than on how you define these inherently slippery terms. — Jeremy Goldberg writes: There's an outright lie right now on the Washington Post homepage. A caption above a graph showing the inflation rate over time states, "Elevated prices coming down, annualized rate shows." The chart shows the current inflation rate is 7.1 percent, down from a high of around 9 percent. Elevated prices are not coming down at all. They just aren't elevating as fast anymore. I asked Jeremy to guess the probability that this was an honest mistake vs. malice. He said (thanks for giving a clear answer!) 60-40 in favor of malice. I think this is pretty high, given that I had to read Jeremy’s comment several times before I realized what the error was supposed to be, but I’ve already said I lean towards the “all the rest of you are extremely paranoid” side of things. — Jiro writes: I opened a thread on dsl: https://www.datasecretslox.com/index.php/topic,8430.0.html People brought up several examples there. You can read the thread. One of the more famous examples was saying that Kyle Rittenhouse crossed state lines with a weapon. There are also a bunch of cases where the media says there's "no evidence" for something that has evidence. Someone also brought up your own example of people "tested for drugs" when they were actually just asked if they used drugs. I would count that as an outright lie, even though you don't. I disagree that being asked if someone used drugs is a "test". Oh god, if saying there’s “no evidence” for something counts as a lie, then every media source in the country stands hopelessly condemned. I did write an article (here) on what the people who use that phrase might be thinking (if you can call it that). I agree the Rittenhouse situation was pretty egregious, though commenters bring up that since he went across state lines and had a weapon, it wasn’t unreasonable for people to assume he brought the weapon across state lines. Still, you wonder whether news sources would have repeated reasonable-sounding-but-didn’t-actually-check slanders about someone they liked. I do think this is a good antidote to some of the “mainstream media is actually very careful and fact-checks everything in their original reporting” takes in the comments section. — David Riceman says: How about Richard Landes's new book "Can the whole world be wrong?" about the many lies in the cognitive war against Israel (e.g. Muhammad Al Dura) See his discussion here for why he thinks this is a good example. — FractalCycle writes: I'm collecting examples from other people, will post ones that seem like real counterexamples as I get them. Here's one from recently: https://forum.effectivealtruism.org/posts/jsByfxvNA4x23stLY/a-letter-to-the-bulletin-of-atomic-scientists Yes, I included this issue with the Bulletin Of Atomic Scientists in my last links post, and they really do come out looking very bad here. See here for more discussion. — Hank Wilbon (writes Partial Magic) writes: I think the false Rolling Stone story a decade ago about the frat gang rape counts as the media explicitly lying, particularly as Rolling Stone is historically known for good fact checking (It is a plot point in the movie Almost Famous), however I think that counts as a "very rare" case and that Scott's claim is correct. I asked “Why? A woman said she had been raped, and Rolling Stone believed her. The woman was making it up, but Rolling Stone wasn't” and Deepa commented “Isn't it the job of a reporter to investigate? And be good at it?” I don’t want to pick on Deepa, but this is what happens when you have an overly expansive definition of “lie”! — TorontoLLB writes: The most straightforward counterexample I can think of is the NBC manipulation of the George Zimmerman 911 call. For example this: "The 9-1-1 operator then asked: "OK, and this guy, is he black, white or Hispanic?", and Zimmerman answered, "He looks black." was changed to: ""This guy looks like he's up to no good. He looks black." In another segment they combined completely separate parts of the call to create an audio clip that presents him as saying ""This guy looks like he's up to no good or he's on drugs or something. He's got his hand in his waistband, and he's a black male." There was other bits of reporting from the major networks that appear to be closer to fraud than selective amplification or choosing what not to report. Enough so that in Twitter threads asking people how they got "red-pilled" person after person refers to the media response to the incident. I haven’t looked into this and I can’t confirm or deny that this is true. I hope everyone finds at least one of these comments obviously fair, and at least another obviously unfair, in a way that encourages you to think more about these issues. 7: Other Comments — Paul writes: What's funny is the Weekly World News - the supermarket tabloid with headlines declaring Bigfoot had been found, and married to a local man's sister!; JFK was still alive, etc. - would pass muster under this analysis. They always had sources report stories to them. Those sources were just batshit crazy. Their strategy was simply not to question them skeptically to poke holes in their story as an ordinary reporter/person would, but to encourage them - "Wow, really, a wedding; what was Bigfoot wearing?" I don't mean to entirely dismiss the distinction you make. But in insisting that not a single story - not even one of the most egregious stories by the most irresponsible, disreputable, of barely-extant publications - is a lie, I think you try to prove too much. In doing so, you retreat so far that you defend only a weak and emasculated position, not any of the broader or more meaningful points implicated by your piece. Thanks for this - I always wondered what those tabloids thought they were doing, and for some reason this matches my model of human psychology better than my previous theories about “maybe they just made it up” - though I bet they do some of that too. — John Buridan writes: I used to have very low priors against conspiracy theories and so was willing to hear out the arguments at length and go back and forth for many weeks and months on a single theory. I would say my conspiracy theory expertise is in creationism and government conspiracies, especially ones involving either Catholicism or Judaism. And I'm okay on one's involving fluoridation, chemtrails, and GMOs etc. One of my housemates was a senior when I was a freshman in college gave me the Adobe illustrator birth certificate shtick, and we went through it together. We downloaded the birth certificate, uploaded it to Adobe illustrator, and saw the weird things. Then I went back to my day job where I was learning Adobe Illustrator. This is maybe 2 weeks later. And what do I find but that when I do this with any PDF, Illustrator renders it in the same janky way? Conspiracy dissolved. I grew up surrounded by people who believed conspiracy theories, although none of those people were my parents. And I have to say that the fact that so few people know other people who believe conspiracy theories kind of bothers me. It's like their epistemic immune system has never really been at risk of infection. If your mind hasn't been very sick at least sometimes, how can you be sure you've developed decent priors this time? Of course, this just all goes back to the dark matter beliefs of people in our outgroup. And the eternal question of where do good priors come from? How do some people's beliefs get so messed up? Thanks for this. I agree that a little bit of experience personally believing conspiracy theories, or knowing people who do, goes a long way. When I was a teenager, I flirted with a lot of pseudoarchaeology theories - think Graham Hancock, underwater pyramids, that kind of thing. I got better, but it left me with a visceral understanding of how people can genuinely believe weird things - not be lying about it, not be secretly making some kind of emotional point about how they hate the system, not be deliberately trying to be as sloppy as possible because you’re a bad person - just genuinely believe it because you tried to reason about it and failed. I think if you haven’t had that experience, then it’s really hard to understand people who have. 8: My Actual Thoughts I should probably try to say, as clearly as possible, what I think. It seems like all of these are different things: Reasoning well, and getting things right
Aduhelm

Aduhelm is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 20, 2021 and August 14, 2025. The archive places it in contexts such as ""The true tragedy of Aduhelm will be that the Alzheimer's Disease research space""; "Tl;DR : Aduhelm sucks"; "Anti-amyloid drugs (like Aduhelm ) don't reverse the disease, and only slow progression a relatively small amount". It most often appears alongside aducanumab, aducanumab, amyloid.

Article page
Aduhelm
Mention count
2
Issue count
2
First seen
August 20, 2021
Last seen
August 14, 2025
August 20, 2021 · Original source
These are highlights from the comments of Adumbrations Of Aducanumab, Details Of The Infant Fish Oil Story, and discussion of those posts elsewhere.
C_B writes:
I agree with this post's overall point that the FDA is not, on average, too lax, and that the Atlantic article's take that the aducanumab approval is a sign of them being too lax is a bad take.
August 14, 2025 · Original source
Aducanumab in phase 1b [77] (19% on my average across cognitive endpoints for the highest two doses) and one of two phase 3 trials [78] (22%, but negative 2% in the other trial, which also gave a lower dose on average).
But biology is messy, and we need to have comfort with complexity. Yes, there’s evidence that tau is responsible for the neurodegeneration in Alzheimer’s disease; no, this doesn’t contradict the amyloid hypothesis. Yes, Biogen screwed up in conducting the aducanumab phase 3 trials and this made the results harder to interpret; no, that doesn’t mean amyloid therapies have completely failed. Yes, it’s taken way too long to get even to this intermediate point of 30% efficacy, due to a combination of overregulation and biology just being damned hard; no, that doesn’t mean we’re on the wrong track with the underlying science.
[77] J. Sevigny et al., “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease,” Nature, vol. 537, no. 7618, pp. 50–56, Sep. 2016, doi: 10.1038/nature19323.
Alexa

Alexa is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 22, 2022 and January 09, 2026. The archive places it in contexts such as "the corporate surveillance (e.g. Alexa, your phone) that accompanies it"; "Alexa doesn’t have that function"; "He dreams of one day breaking free of his dependence on me and learning to command Alexa himself". It most often appears alongside 2020 election, 2022 book review contest, 2122.

Article page
Alexa
Mention count
2
Issue count
2
First seen
July 22, 2022
Last seen
January 09, 2026
July 22, 2022 · Original source
Cover of The Society of the Spectacle He never outright explains why he thought photos and film were more pernicious than newspapers or radio, but I imagine the advertising industry played a major role. We’ve grown accustomed to GoDaddy ads and ALL CAPS YouTube titles, but Mad Men shenanigans were a worrisome development at the time. It must’ve been highly alarming to see such brazen manipulation of the public. Whatever the reasoning, we now arrive at one definition of the spectacle: "The spectacle is capital accumulated to the point that it becomes images." Also: “The spectacle is not a collection of images; it is a social relation between people that is mediated by images.” Well, that’s about as clear as Flint water. Here’s something meatier: "In all of its particular manifestations — news, propaganda, advertising, entertainment — the spectacle represents the dominant model of life." If you’re familiar with Girard, that is a huge statement. [3] Girardian mimetic desire is triangular; there is you (the desirer), the object (of desire), and the model (another person who also desires the object). Most of our desires are rooted in imitation. Nobody has to tell you to want steak or sex, but almost everything else is learned. How does everybody know that they should want a Rolex or a Rolls Royce? There’s no genetic imperative for luxury goods. You acquire those tastes from the people around you. Or you used to, at least. Before the spectacle, your models, mentors, and rivals were real people you knew in real life. Now we have an acronym for that - IRL - because reality is everywhere in retreat. This is not a small thing. What we desire is at the core of who we are. What do you want out of life? What kind of person do you want to be? For the entirety of human history, those questions found answers close at hand. Your local community was your world, for better and worse. Now we are global citizens with global perspectives, and it’s difficult to overstate how much that changes what it means to be human. Imprisoned in a flattened universe bounded by the screen of the spectacle that has enthralled him, the spectator knows no one but the fictitious speakers who subject him to a one-way monologue about their commodities and the politics of their commodities. The spectacle as a whole serves as his looking glass. What he sees there are dramatizations of illusory escapes from a universal autism. The spectacle’s estrangement from the acting subject is expressed by the fact that the individual’s gestures are no longer his own; they are the gestures of someone else who represents them to him. Now our role models are media creations. Some are literal fictional characters (James Bond); others are nominally real people (Kylie Jenner). But both are merely representations - images usurping an essential formative role. ‘William Shatner’ and ‘Robert Downey, Jr.’ are only marginally more real than Captain Kirk and Tony Stark, yet they occupy way more headspace than people that live down the street. Most people can name more celebrities, in more detail, than people they’ve known in person. I know the names of Will Smith’s kids - I don’t even know if my best friends from high school have any. This is an issue of The Map and The Territory. Pre-modern Maps were narrow but deep. You might have had only a vague notion of ‘Africa’ or ‘The Pope’, but you knew every square inch of the town you lived in. Spectacular Maps are broad but shallow, and they are drawn for us by spectacular hands. The average person ‘knows’ way more about Africa now, but how well does that knowledge reflect the facts on the ground? Meanwhile, firsthand reality has been reduced to the narrow slices connecting house to car to work, with precious few exceptions. The Society Of The Spectacle is one long lament for this loss of The Real, although Debord doesn’t state it as such. Borrowing again from The Uruk Machine, this sense of loss tracks with the gradual displacement of metis [4] by episteme [5],[6]. III. Everything New Is Old Again Debord has a lot to say about the ‘falsification of the world’: The first stage of the economy’s domination of social life brought about an evident degradation of being into having — human fulfillment was no longer equated with what one was, but with what one possessed. The present stage, in which social life has become completely dominated by the accumulated productions of the economy, is bringing about a general shift from having to appearing — all ‘having’ must now derive its immediate prestige and its ultimate purpose from appearances. As he might have put it - we have graduated from conspicuous consumption to consuming conspicuousness. Spectacular technology has not dispersed the religious mists into which human beings had projected their own alienated powers, it has merely brought those mists down to earth, to the point that even the most mundane aspects of life have become impenetrable and unbreathable. In the spectacle, a part of the world presents itself to the world and is superior to it. The spectacle is simply the common language of this separation. Spectators are linked solely by their one-way relationship to the very center that keeps them isolated from each other. The spectacle thus reunites the separated, but it reunites them only in their separateness. These themes are familiar to us by now. It’s not exactly news that people are getting more isolated and untethered by the year. What is striking to me is not what he is saying, but when he is saying it. Anybody with sense has spent time thinking about how to manage the challenges of modern life. We talk about digital minimalism and social media fasts. Turn off your phone. Get outside and touch grass. Go see people in meatspace. Be present. All great advice. But what are we envisioning, when we imagine a healthy connection to The Real? For most of us, we are picturing life as it was lived… right around the time Debord was saying that everything is phony and toxic. What does the average person think of as the peak of journalistic integrity in America? Probably Vietnam and Watergate - right after this was written. When we mock Millennials and Zoomers, what standard are we measuring them by? The Greatest Generation, who were running the show by the late sixties. In terms of self-reliance and resilience, the average adult in 1967 would be a massive outlier in 2022. Yet here is Debord, saying in no uncertain terms that this American ideal was fraudulent and devoid of meaning. What have we lost? Every era has its cynics, doomsayers, Luddites, and misanthropes. Maybe Debord was just a Boomer’s Boomer, railing against progress and the passage of time. But I don’t think so. We’ve all felt the shockwaves of the Internet explosion. Life is different now. It takes an act of will to put down your phone so you can focus on the TV. Low battery is an emergency. Losing signal is bereavement. Navigating without GPS is an anxiety attack. Do you remember what it was like, not so long ago? How exciting it was to play videogames with someone a thousand miles away? How cool it was the first time you streamed a movie on an airplane? That sense of possibility and promise, like all the world was in the palm of your hand? How quickly things change. For maybe the first time in history, most people are apprehensive about the relentless march of technology. While we’ve always been afraid of advances in weaponry, it’s starting to feel like everything is being weaponized. Who truly believes the metaverse will be a positive step for humanity? Who now is excited at the prospect of gene editing, AI, or transhumanism? There appears to be a growing sentiment along the lines of ‘MGTOW for modernism’. We hope for the best, but 2122 is shaping up to be some unholy amalgam of Gattaca, The Matrix, and Minority Report. Sometimes it seems like the world we grew up in is categorically distinct from the world we inhabit. But I’m sure Debord would argue that we are merely experiencing an intensification of a process that has been in motion longer than any of us have been alive. Pre-spectacular society has already passed beyond living memory. Soon we will hit another inflection point - where no one alive even knew someone who lived before the spectacle. All of human history is now before and after; it will soon become literally impossible to understand the inner life and daily reality of pre-modern man - if it’s not already. As an example: how much of your daily environment, as a percentage, do you truly understand? Look around the room and reflect on how “even the most mundane aspects of life have become impenetrable and unbreathable.” Your kitchen and your medicine cabinet are filled with mystical objects. Hell, just look at what’s on your person. The phone in your hand, the cash in your wallet, the clothes on your back, the food in your belly - how many lifetimes would it take to truly grok the building blocks of everyday existence? Compare that to, say, a homesteader. It really hasn’t been that long since people lived in a comprehensible universe. Our collective knowledge of the universe has deepened tremendously, but theoretical physics is only less slightly hermetical than the occult beliefs it replaced. It is notionally true that anyone could go get a Ph.D. and verify our working model of the cosmos. But in practice, the science is received wisdom, taken on faith. Our belief in the God Particle is functionally indistinguishable from the belief in God of ages past. It’s worth noting that our current theories will surely be supplanted in a century or three. They are placeholders for better, truer ideas. And so our greater grasp of the wider world has less value than we think, while our day-to-day grows ever more opaque. Is it any wonder epistemic learned helplessness is a thing? IV. With Typical Extravagance Debord was also ahead of the curve on commoditization: This constant expansion of economic power in the form of commodities transformed human labor itself into a commodity, into wage labor, and ultimately produced a level of abundance sufficient to solve the initial problem of survival — but only in such a way that the same problem is continually being regenerated at a higher level. Economic growth has liberated societies from the natural pressures that forced them into an immediate struggle for survival; but they have not yet been liberated from their liberator. Once his workday is over, the worker is suddenly redeemed from the total contempt toward him that is so clearly implied by every aspect of the organization and surveillance of production, and finds himself seemingly treated like a grownup, with a great show of politeness, in his new role as a consumer. Debord correctly perceived the totalitarian nature of spectacular capitalism. Your time, your attention, your opinions - all are bought and sold, and can be influenced to better facilitate such transactions. He would have been totally unsurprised by the rise of Big Data and the corporate surveillance (e.g. Alexa, your phone) that accompanies it. Every piece of your life is a commodity. Every moment that you are not producing or consuming is a missed opportunity. Never fear - someone, somewhere is going to find a way to solve that ‘need’. Nothing is spared. Even opposition is assimilated: Complacent acceptance of the status quo may also coexist with purely spectacular rebelliousness — dissatisfaction itself becomes a commodity as soon as the economy of abundance develops the capacity to process that particular raw material. Once again, Debord is shockingly prescient in noting that the conflicts of our time are largely distractions from bigger systemic issues: Fallacious archaic oppositions are revived — regionalisms and racisms which serve to endow mundane rankings in the hierarchies of consumption with a magical ontological superiority — and pseudoplayful enthusiasms are aroused by an endless succession of ludicrous competitions, from sports to elections. Genuine grassroots movements (Occupy, the Tea Party, BLM, Canadian truckers) almost always fizzle out without accomplishing anything of substance. They will either be ignored, crushed, or co-opted. Any remnants that endure will be reduced to figureheads that offer ‘representation’ for a point of view without actually producing any change. (‘The Squad’, Rand Paul, etc…) If the extremes of either side gain enough momentum to pose a threat, they will face a united front from the establishment wings of both parties (Bernie, Trump). It’s fashionable at the moment to blame the Woke Left for the politicization of everything, but we’ve all been around long enough to know better. It’s the same shit, different decade. During the Bush years, it was the left who opposed unending wars, government overreach, and media gaslighting. Today those positions are often considered right wing, but only because the pendulum of power has swung in the other direction. Moloch pursues its own goals, wearing whatever ideological guise it deems most effective. From Debord’s perspective, everything is becoming politicized because everything is getting monetized. In the integrated spectacle, the primary concerns of the State are economic, so the personal turning political is simply a downstream effect of the growth of capitalism. V. A Short History of Time It would do Debord a disservice to reduce his work to ammunition in our present disputes. There are two whole chapters in the book devoted to time as a historical development. It’s not something we think about much, but time and history had to be invented. Before the beginning, humanity lived in what Debord calls cyclical time. Countless generations came and went, because nobody was counting. Survival was the name of the game; to be or not to be was the only question. Eventually we formed early societies, which brought into being a ruling class that had the freedom to take actions above and beyond the daily grind: The owners of this historical surplus value are the only ones in a position to know and enjoy real events. Separated from the collective organization of time associated with the repetitive production at the base of social life, this historical time flows independently above its own static community. This is the time of adventure and war, the time in which the masters of cyclical society pursue their personal histories; it is also the time that emerges in the clashes with foreign communities that disrupt the unchanging social order. History thus arises as something alien to people, as something they never sought and from which they had thought themselves protected. The murkiness of pre-civilization was shaped into coherence by these rulers, who used their unique agency to literally make history: The succession of generations within a natural, purely cyclical time begins to be replaced by a linear succession of powers and events. This irreversible time is the time of those who rule, and the dynasty is its first unit of measurement. With writing there appears a consciousness that is no longer carried and transmitted directly among the living — an impersonal memory, the memory of the administration of society. ‘Writings are the thoughts of the state; archives are its memory’ (Novalis). The owners of history have given time a direction, a direction which is also a meaning. But this history develops and perishes separately, leaving the underlying society unchanged, because it remains separated from the common reality. Over time, these narratives gathered a religious dimension. This helped legitimize the rule of regimes, but it also changed the way ordinary people saw themselves in the world. Although still living in cyclical time, they gained purpose through a spiritual journey culminating in Heaven. The clashes of the Mediterranean peoples and the rise and fall of the Roman state gave rise instead to semihistorical religions, which became a new armor for separate power and basic components of a new consciousness of time. The Middle Ages, an incomplete mythical world whose consummation lay outside itself, is the period when cyclical time, though still governing the major part of production, really begins to be undermined by history. An element of irreversible time is recognized in the successive stages of each individual’s life. Life is seen as a one-way journey through a world whose meaning lies elsewhere: the pilgrim is the person who leaves cyclical time behind and actually becomes the traveler that everyone else is symbolically. The Renaissance created a profound break with this mythic raison d'être and reoriented man towards the accumulation of knowledge as a species: The Renaissance was a joyous break with eternity. Though seeking its heritage and legitimacy in the ancient world, it represented a new form of historical life. Its irreversible time was that of a never-ending accumulation of knowledge… This transformation of our relationship with history and progress was accompanied by the rise of the bourgeoisie: The bourgeoisie is associated with a labor time that has finally been freed from cyclical time. With the bourgeoisie, work becomes work that transforms historical conditions. The bourgeoisie is the first ruling class for which work is a value. The victory of the bourgeoisie is the victory of a profoundly historical time, because it is the time corresponding to an economic production that continuously transforms society from top to bottom. So long as agrarian production remains the predominant form of labor, the cyclical time that remains at the base of society reinforces the joint forces of tradition, which tend to hold back any historical movement. But the irreversible time of the bourgeois economy eradicates those vestiges throughout the world. History, which until then had seemed to involve only the actions of individual members of the ruling class, and which had thus been recorded as a mere chronology of events, is now understood as a general movement — a relentless movement that crushes any individuals in its path. Irreversible time initially appeared at the societal level as a narrative of events. The bourgeoisie brought irreversible time to the masses. Progress became something that we personally experience in the form of rapid technological innovation. It is hard to miss the motion of history when you go from horses to space travel in a single lifetime. History thus became as much about things as events. Eli Whitney and Thomas Edison took their places alongside generals and heads of state in our narrative of who we are and where we’re going. Our notion of progress became dominated by the economic prejudice. We talk about raising the standard of living and lifting people out of poverty - laudable goals, to be sure - but we deliver them from physical privation into deprivation of a different kind. One way that deprivation manifests is in our current conception of time: Pseudocyclical time is associated with the consumption of modern economic survival — the augmented survival in which everyday experience is cut off from decisionmaking and subjected no longer to the natural order, but to the pseudo-nature created by alienated labor. It is thus quite natural that it echoes the old cyclical rhythm that governed survival in preindustrial societies, incorporating the natural vestiges of cyclical time while generating new variants: day and night, work and weekend, periodic vacations." As capitalism commoditized time itself, we recreated cyclical time with the standard work week. But this artificial substitute has been about as successful as vegan chicken nuggets. It’s not the same, and it never will be. The workday used to be determined by the work, but now the work is determined by the workday. And everyone has to work, not because we need what they produce, but because we need them to spend - else the whole thing comes crashing down. Irreversible time keeps marching on, giving us new widgets and new wonders, but the continual churn of innovation masks the stifling sameness of spectacular progress. We know something is missing, but we lack the capacity to understand or express the problem. This individual experience of a disconnected everyday life remains without language, without concepts, and without critical access to its own past, which has nowhere been recorded. Uncommunicated, misunderstood and forgotten, it is smothered by the spectacle's false memory of the unmemorable. VI. The Coming Revolution Debord spends a good chunk of words describing how the spectacle has affected art [7] and physical space, but you can guess the gist by now. Everything’s fake, everything’s worse, everything’s changing but also the same. The last topic of the book worth discussing is the imminent socialist revolution. Debord walks us through the various ways that Marxism has been done wrong, then attempts to offer an alternative. He goes into a fair amount of detail, but it boils down to this: The anarchists properly rejected society in its entirety, but remained dogmatically attached to a 'one size fits all' mentality and failed to organize in an effective manner.
January 09, 2026 · Original source
I never did figure out how the police got called. My first guess was that one of the twins had gotten their hands on a phone and dialed random things, but neither my nor my wife’s call history showed anything incriminating. My second guess was that they’d screamed at Alexa so hard that it called emergency services, but the documentation says Alexa doesn’t have that function. Maybe a neighbor called and the police got the location wrong, I don’t know.
I do have a pretty good idea about the screaming, though. When Kai demanded “the sun song”, I had accidentally told Alexa to play Raffi’s version of Mister Golden Sun instead of SuperSimpleSongs’ version. Kai did not consider this a sufficiently faithful rendition, and made his displeasure clear to everyone in the neighborhood at six in the morning. Then Lyra didn’t like that Kai was screaming, and started screaming too. By the time I realized the song mishap, I couldn’t rectify my mistake, because they were screaming too loud for Alexa to hear my commands (and too loud for them to notice if the song changed anyway).
Often it’s the songs. They like songs, but rarely the same ones, and their tastes can change mid-note. I try my best to keep up, but after switching back and forth between a pair of songs three or four times, as Kai (it’s always Kai) vacillates over which one he wants, sometimes I give up and let him scream it out. He dreams of one day breaking free of his dependence on me and learning to command Alexa himself. In this he is constantly frustrated - he can’t pronounce the incantations with the required precision. Some of the hardest I’ve ever laughed was listening to him trying desperately, pleadingly, to make Alexa play Rockin’ Robin. “Asasa, play Rabu Rabu! Asasa, play Rogu Roku! Asasa, play Ruku Roobu!” Alas, his beloved refuses to so much as acknowledge his existence.
Ambien

Ambien is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 29, 2023 and June 08, 2023. The archive places it in contexts such as "Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien"; "That drug would be more than four times stronger than Ambien!". It most often appears alongside Adderall, ACX survey, Bay Area.

Article page
Ambien
Mention count
2
Issue count
2
First seen
March 29, 2023
Last seen
June 08, 2023
March 29, 2023 · Original source
The first fruit of their labor is DEA-407, which makes it hard for telemedicine doctors to prescribe controlled substances. Controlled substances are drugs like Adderall, Ritalin, Xanax, or Ambien that the government has declared to be potentially addictive. The new rules say that telemedicine doctors can no longer prescribe these (or, in some cases, can prescribe them one time in an emergency).
June 08, 2023 · Original source
Consider a claim that the difference between treatment and control groups was “only as big, in terms of effect size, as the average height difference between men and women - just a couple of inches” (I think I saw someone say this once, but I’ve lost the reference thoroughly enough that I’m presenting it as a hypothetical). That drug would be more than four times stronger than Ambien!
amphetamine

amphetamine is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 25, 2021 and July 19, 2021. The archive places it in contexts such as "difference between amphetamine and methamphetamine"; "amphetamine (Adderall), which despite its fearsome reputation as a street drug". It most often appears alongside Adderall, FDA, ADHD.

Article page
amphetamine
Mention count
2
Issue count
2
First seen
January 25, 2021
Last seen
July 19, 2021
January 25, 2021 · Original source
In the 1950s, a shady outfit called Obetrol Pharmaceuticals made a popular over-the-counter diet pill called Obetrol. If you're familiar with any of: the 1950s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?" and the answer is yes, loads of them. Obetrol was a mix of four different amphetamine salts: racemic amphetamine sulfate, dextroamphetamine sulfate, methamphetamine saccharate, and methamphetamine hydrochloride. Why did they need four different kinds of speed? I'm not sure. The uncharitable explanation is: for the same reason Dr. Nick's Cure-All Home Remedy has twelve different herbs, ie customers think things with more ingredients are better.
By the 1970s, people figured out meth was bad, so Obetrol replaced their two methamphetamine salts with two more kinds of non-methylated amphetamine. But the FDA continued to crack down, and although the historical paper trail goes kind of dark, it looks like Obetrol had disappeared by the 1980s.
Treating ADHD with amphetamines was hardly a new invention. Psychiatrists had been doing it since the 1930s, albeit with slightly different drugs. Remember, many organic chemicals come in two versions, a "right-handed" or "d" version and a "left-handed" or "l" version. Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice throughout the mid-20th century. So why was it Adderall - a weird combination of four different salts selected kind of at random by a sketchy diet pill company - that caught on?
July 19, 2021 · Original source
There are common reports of severe side effects from recreational ketamine users, of which the best known are urinary (eg cystitis) and hepatic. It would be concerning if clinical use caused these at anywhere near the same rate. But we should remember that eg recreational amphetamine abuse produces all sorts of terrible side effects, but essentially none of them carry over to clinical amphetamine use (eg Adderall for ADHD). This is mostly because recreational users take doses orders of magnitude higher; “the dose makes the poison”.
In general, I’m not very concerned about this with most patients, for a few reasons. First are the reports from expert prescribers, who say basically none of their patients ever get addicted. Second is the general experience of using addictive drugs in psychiatry – for example, amphetamine (Adderall), which despite its fearsome reputation as a street drug is rarely abused by patients who get it by prescription. Addiction is a biopsychosocial process and people without genetic and psychological predispositions to addiction are usually able to use these chemicals safely.
Android

Android is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 13, 2023 and November 10, 2023. The archive places it in contexts such as "Also on their list were Facebook ads and the Android"; "one of the tools which lets you build native apps for iPhone and Android". It most often appears alongside Twitter, #EEGManyLabs, 23andme.

Article page
Android
Mention count
2
Issue count
2
First seen
September 13, 2023
Last seen
November 10, 2023
September 13, 2023 · Original source
This book taught me that everyone always predicts Elon will fail at whatever he does. When he started the original X (later PayPal), everyone who knew anything about finance told him he would fail. Just because he was a hotshot coder who could write software didn’t mean he could navigate the totally-different and heavily-regulated world of finance. Elon, who started out indeed knowing nothing about finance, learned on the job and got a $200 million exit. Gawker voted Tesla #1 in their Biggest Tech Flops of 2007 (also on their list were Facebook ads and the Android . . . maybe journalists don’t actually understand tech?)
November 10, 2023 · Original source
This is a pure-front-end-web-app with all the sentences hard-coded. I don't see any issue with getting accurate timing: the timing could be done client side (as others have said) and I really think even a web-app like this would be high-fidelity enough for human-scale interactions. The only issue is security. I don't think you could make a web-app that's secure against someone cheating if they really wanted to. If we're measuring biases people might be trying to hide, this would be an issue. The solution would be to make a native app of some sort. I'd probably use one of the tools which lets you build native apps for iPhone and Android.
AstraZeneca

AstraZeneca is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 24, 2022 and May 18, 2022. The archive places it in contexts such as "US approves AstraZeneca vaccine"; "gotten money from AstraZeneca". It most often appears alongside 538, ACX, ADHD.

Article page
AstraZeneca
Mention count
2
Issue count
2
First seen
January 24, 2022
Last seen
May 18, 2022
January 24, 2022 · Original source
COVID 23. Fewer than 10K daily average official COVID cases in US in December 2021: 30% 24. Fewer than 50K daily average COVID cases worldwide in December 2021: 1% 25. Greater than 66% of US population vaccinated against COVID: 50% 26. India's official case count is higher than US: 50% 27. Vitamin D is not generally recognized (eg NICE, UpToDate) as effective COVID treatment: 70% 28. Something else not currently used becomes first-line treatment for COVID: 40% 29. Some new variant not currently known is greater than 25% of cases: 50% 30. Some new variant where no existing vaccine is more than 50% effective: 40% 31. US approves AstraZeneca vaccine: 20% 32. Most people I see in the local grocery store aren't wearing a mask: 60%
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
azithromycin

azithromycin is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 17, 2021 and February 01, 2023. The archive places it in contexts such as "plus the antibiotic azithromycin"; "vitamin D or azithromycin cured COVID this effectively"; "azithromycin, oseltamavir, and some vitamins". It most often appears alongside Alexandros Marinos, Aref, Argentina.

Article page
azithromycin
Mention count
2
Issue count
2
First seen
November 17, 2021
Last seen
February 01, 2023
November 17, 2021 · Original source
Click to expand. # is how many people were in the smallest relevant group (eg if there were 20 people in placebo and 10 in ivermectin, it was 10). Dose is ivermectin dose x number of days. Tested w/ is what drugs were given alongside ivermectin; compare is what drugs were in the “placebo” group (I excluded some very common things like paracetamol). %-PCR7 is what percent of patients had a negative PCR test (indicating recovery) after 7 days (though if 7 wasn’t available, I accepted anything from 6-12); the (I) and (P) are ivermectin and placebo groups. R is the ratio - green if statistically significant, red otherwise. DaysPCR is how many days it took to get a negative PCR test. Days to -sym are how many days it took symptoms to resolve. -outc is some serious negative outcome in the study, either clinical worsening, hospitalization, or death. I was inconsistent which one I chose, trying to pick whichever I thought struck a balance between high sample size and severity. Since this was almost never significant, I made it blue if it favored ivermectin and orange if it favored placebo (which it never did; there is no orange). Lowest p is the lowest p-value in the study for one of the headline results. 1o+ is whether the primary outcome was positive or not. I made this very quickly and unprincipledly and I am sure there are a lot of errors; please forgive me. Of studies that included any of the endpoints I recorded, ivermectin had a statistically significant effect on the endpoint 13 times, and failed to reach significance 8 times. Of studies that named a specific primary endpoint, 9 found ivermectin affected it significantly, and 12 found it didn’t. But that’s still pretty good. And “doesn’t affect to a statistically significant degree” doesn’t mean it doesn’t work. It might just mean your study is too small for a real and important effect to achieve statistical significance. That’s why people do meta-analyses to combine studies. And the ivmmeta people say they did that and it was really impressive. All of this is still basically what things would look like if ivermectin worked. But of course we can’t give every study one vote. We’ve got to actually look at these and see which ones are good and which ones are bad. So, God help us, let’s go over all thirty of the ivermectin studies in this top panel of ivmmeta.com. (if you get bored of this, scroll down to the section called “The Analysis”) The Studies Elgazzar et al: This one isn’t on the table above, but we can’t start talking about the others until we get it out of the way. 600 Egyptian patients were randomized into six groups, including three that got ivermectin. The ivermectin groups did substantially better: for example, 2 vs. 20 deaths in ivermectin group 3 vs. non-ivermectin group 4. There were various other equally impressive outcomes. Unfortunately, it’s all false. Some epidemiologists and reporters were able to obtain the raw data (it was password-protected, but the password was “1234”), and it was pretty bizarre. Some patients appeared to have died before the trial started; others were arranged in groups of four such that it seemed like the authors had just copy-pasted the same four patients again and again. Probably either the study never happened, or at least the data were heavily edited afterwards. You can read more here. A lot of the apparent benefit of ivermectin in meta-analyses disappeared after taking out this paper (though remember, this isn’t even on the table at the top of the post, so it doesn’t directly affect that). Since the Elgazzar debacle, a group of researchers including Gideon Meyerowitz-Katz, Kyle Sheldrake, James Heathers, Nick Brown, Jack Lawrence, etc, have been trying to double-check as many other ivermectin studies as possible. At least three others - Samaha, Carvallo, and Niaee - have similar problems and have been retracted. Those studies were all removed before I screenshotted the table above, and they’re not on there. But everybody is pretty paranoid right now and looking for fraud a lot harder than they might be in normal situations. Moving on: Chowdury et al: Bangladeshi RCT. 60 patients in Group A got low-dose ivermectin plus the antibiotic doxycycline, 56 in Group B got hydroxychloroquine (another weird COVID treatment which most scientists think doesn’t work) plus the antibiotic azithromycin. No declared primary outcome. Ivermectin group got to negative PCR a little faster than the other (5.9 vs. 7 days) but it wasn’t statistically significant (p = 0.2). A couple of other non-statistically-significant things happened too. 2 controls were hospitalized, 0 ivermectin patients were. This is a boring study that got boring results, so nobody has felt the need to assassinate it, but if they did, it would probably focus on both groups getting various medications besides ivermectin. None of these other medications are believed to work, so I don’t really care about this, but you could tell a story where actually doxycycline works great at addressing associated bacterial pneumonias, or where HCQ causes lots of side effects and that makes the ivermectin group look good in comparison, or whatever. Espitia-Hernandez et al: Mexican trial which is probably not an RCT - all it says is that “patients were voluntarily allocated”. 28 ended up taking a cocktail of low-dose ivermectin, vitamin D, and azithromycin; 7 were controls. On day ten, everyone (!) in the experimental group was PCR negative; everyone (!) in the control group was still positive. Also, symptoms in the experimental group lasted an average of three days; in the control group, more like 10. These results make ivermectin look amazingly super-good, probably better than any other drug for any other disease, except maybe stuff like vitamins for treatment of vitamin deficiency. Any issues? We don’t know how patients were allocated, but they discuss patient characteristics and they don’t look different enough to produce this big an effect size. The experimental group got a lot of things other than ivermectin, but I would be equally surprised if vitamin D or azithromycin cured COVID this effectively. It deviated from its preregistration in basically every way possible, but you shouldn’t be able to get “every experimental patient tested negative when zero control patients did” by garden-of-forking-paths alone! But this has to be false, right? Even the other pro-ivermectin studies don’t show effects nearly this big. In all other studies combined, ivermectin patients took an average of 8 days to recover; in Espitia-Hernandez, they took 3. Also, it’s pretty weird that the entire control group had positive PCRs on day 10 - in most other studies, a majority of people had negative PCRs by day 7 or so, regardless of whether they were control or placebo. Everything about this is so shoddy that I can easily believe something went wrong here. I don’t have a great understanding of this one but I don’t trust it at all. Luckily it is small and non-randomized so it will be easy to ignore going forward. I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
February 01, 2023 · Original source
Gideon (correctly) phrased this as a non-sinister albeit potentially weird misstep by the study authors, but in trying to summarize Gideon, I (incorrectly) phrased it as a sinister attempt to inflate results. After looking into it, I think Alexandros is completely right and I was completely wrong. Although I sometimes get details wrong, this one was especially disappointing because I incorrectly tarnished the reputation of Biber et al and implicitly accused them of bad scientific practices, which they were not doing. I believed I was relaying an accusation by Gideon (who I trust), but I was wrong and he was not accusing them of that. I apologize to Biber et al, my readers, and everyone else involved in this. My only reservation is that I don’t want to say too strongly that Gideon’s critique is wrong: I haven’t looked through the study documents enough to say with certainty that Alexandros’ reanalysis of the protocol issues is correct (though the superficial check I’ve done looks that way). But my mistakes are completely separate from anything Gideon did and definitely real and egregious. Cadegiani et al (Alexandros 50% right) Flavio Cadegiani did several studies on ivermectin in Brazil; I edited this section in response to criticism by Marinos and others, but the earliest version I can find on archive.is (I can’t guarantee it was the first I wrote) said: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. Also in Cadegiani news: he apparently has the record for completing one of the fastest PhDs in Brazilian history (7 months), he was involved in a weird scandal where the Brazilian government tried to create a COVID recommendation app but it just recommended ivermectin to everybody regardless of what input it got, and he describes himself as: …the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . Which sounds great, except that it looks like most of this is that the control group had a shockingly high mortality rate, much higher than makes sense even in the context of severe COVID. I think the charitable explanation here is that he made this data up too. But the Brazilian Parliament seems to be going with an uncharitable explanation, seeing as they have recommended that Cadegiani be charged with crimes against humanity. Anyway, let’s not base anything important on the results of this study. You can find Alexandros’ full critique here, but again I’ll try to summarize it as best I can. Alexandros is unhappy with my portrayal of Cadegiani’s background. I cite details that make him look strange and maybe fake, but there are other details that make him seem more impressive, like that he won gold medals at a Brazilian Scientific Olympiad.
Carvallo said that zero people in the treatment group of his study got COVID, compared to 58% of people in the control group. This is a pretty implausibly big effect, even by the standards of other pro-ivermectin studies, although I don’t know if anyone else tried the exact same preventative protocol as Carvallo. I think this is a more nuanced story than Alexandros’ version where Buzzfeed just doesn’t know that sometimes studies happen at more than one hospital. Is fraud the best explanation? I think Alexandros thinks of Carvallo as just not keeping very good records, so he doesn’t have raw data, and probably mixed up his numbers a few times or gave false numbers, and didn’t have anything to send his collaborators when they asked. I think this is maybe possible, although it seems suspicious that he falsely said Dr. Lombardo was involved, falsely claimed the hospital involved was doing a different trial, and got very implausible results. I can imagine weird chains of events that would cause all of these things through honest misunderstandings. But they don’t seem like the best explanation. After discussing this with Alexandros, he objects to my use of the term “known fraudster”. Perhaps I should have said “highly credibly suspected fraudster” instead, although in a Bayesian sense nothing can ever be 100% and at some point plausibility shades imperceptibly into knowledge. Still, I feel like my description here was more accurate than Alexandros’, which just mentions the hospital approval issue and says nothing about any of the rest of this in a thousand word subsection about this study in particular. I did err in saying the Carvallo paper was retracted. According to the article: After BuzzFeed News raised questions about how the study’s data was collected and analyzed, a representative from the Journal of Biomedical Research and Clinical Investigation, which published the results, said late Monday, “We will remove the paper temporarily.” A link was removed from the table of contents — but was reinstated by Thursday. The journal’s explanation, provided after this story was published, was that the author “informed us that he has already provided the evidence of his study to the media.” I apologize for the error. Elalfy et al (still disagree with Alexandros) I described this as: As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable […] There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. In the summary post, Alexandros’ entire criticism of my coverage of this trial, one of the seven trials he focuses on as most unfairly covered and uses as the lynchpin of his argument that I am morally culpable for disastrously bad reporting, is: [Elalfy et al] are accused of incompetence for failing to randomize their groups multiple times in Scott’s piece. The paper writes in six separate places that it is not reporting on a randomized trial, amongst them on a diagram that Scott included in his own essay. Hard to imagine how else they could have made it clear. In his full post on this, he goes line by line to point out all the places they say they are non-randomized, pausing to snark about how dumb I am for not noticing each time4. But he never addresses the actual source of my confusion, which is the part of the paper where it says that: Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment. If this was done as described, it should be an (almost) random trial; patients who come in on Wednesdays shouldn’t systematically differ from patients who come in on Thursdays5. But in fact, it looks (assuming I am understanding a very ambiguous table correctly) like there are very large pre-existing differences between the groups, sufficient to explain the entire result. If they in fact followed their days-of-the-week protocol, and it was random as expected, then I’m misunderstanding the table seeming to show very large differences, and they have indeed found evidence for ivermectin’s efficacy. If they didn’t follow their day-of-the-week protocol and it’s non-random, then maybe I’m understanding the table correctly and their groups had large differences to begin with and the fact that they had large differences at the end of the trial doesn’t demonstrate anything about ivermectin. This is all I was trying to say in the post, and instead of having any opinion on it Alexandros just makes fun of me for saying it. I think our actual crux is that Alexandros thinks a table of big differences between the groups has to be post-treatment (based on how big the differences are), whereas I’m not sure (because it’s unclear in the study, and also because the authors describe what could be a randomization method but also go on and on about how nonrandom they are). This is why I thought it mattered how random it was! Maybe instead of mocking me for this, you can admit it’s an important and relevant question! Ghauri et al (still disagree with Alexandros) I describe this as: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. Alexandros notes that these are three differences between experimental/control groups, out of 33 listed characteristics that could have been different. There is approximately a 23% chance (he calculates) that you could get these differences by chance. He accuses me of failing to do a formal Carlisle test - the usual test you would use to determine whether weird differences between randomized groups are because of fraud - instead eyeballing it and getting it wrong. Here I do want to defend myself: I am not accusing Ghauri et al of fraud. In fact, this would be nonsensical: they admit they are assigning patients nonrandomly. Carlisle tests are usually done to show that something about group assignment is impossible (and therefore fraudulent) in a fair random assignment. But these people aren’t claiming to have done a fair random assignment, so I’m not sure what a Carlisle test would prove. My argument is more like: this is nonrandom, therefore we should expect it to be unfair. It is unnecessary, but helpful, to note an actual apparent unfairness - there’s some evidence they gave the ivermectin to less severe patients (as measured by corticosteroid use). Therefore, we can’t necessarily trust this to be a fair trial (which it was never really claiming to be). In the end I kept Ghauri as an okay study, although GMK didn’t so it ended out trashed in the final analysis anyway. I think my thinking was that I never claimed to be only looking at RCTs, so this non-RCT whose between-group-differences confirmed that it was indeed a non-RCT with all the risk of bias that entails, didn’t necessarily need to be ruled out. Still, I don’t think I was wrong to mention this possibility, and I think Alexandros was wrong to suggest that I needed to do extra tests for this to be fair. Borody et al (still disagree with Alexandros) I described this as: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. Alexandros lists his full concerns here. My summary: Scott is being incredibly disrespectful to the authors, who are in fact a legendary gastroenterologist who invented life-saving h. pylori therapy and a brilliant immunologist who invented a well-regarded bronchitis vaccine (in particular, in describing their control group, I said “this is not how you control group, @#!% you”.
Big Mac

Big Mac is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 03, 2021 and March 10, 2023. The archive places it in contexts such as "Big Mac to determine how a country’s currency is doing?"; "unsubsidized Big Mac would cost $13". It most often appears alongside Steven Pinker, Wikipedia, 9-11.

Article page
Big Mac
Mention count
2
Issue count
2
First seen
March 03, 2021
Last seen
March 10, 2023
March 03, 2021 · Original source
27: Maybe you’ve heard of the Big Mac Index, where economists use the price of a Big Mac to determine how a country’s currency is doing? And maybe you’ve heard of Goodhart’s Law, where anything that becomes a target gets manipulated? Yeah, Argentina is accused of pressuring McDonalds to underprice Big Macs to get better terms on its debt.
March 10, 2023 · Original source
31: The Big Mac subsidy - one of my least favorite types of argument is when people argue something is bad because “you think it costs $1, but actually without government subsidies it would cost $100, you’re literally demanding that taxpayers subsidize your evil lifestyle”. And then you ask them for proof, and either they completely made it up, or by “government subsidy” they mean “the government doesn’t force the companies that make it to address all harms caused by its consumption, including harms no other company has to address, and harms I just made up right now, and harms from the fact that it makes me sad and I price my sadness at one billion dollars”. Anyway, the people who say that an unsubsidized Big Mac would cost $13 are definitely doing all of this.
Brighter

Brighter is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 01, 2023 and February 27, 2025. The archive places it in contexts such as "A company called Brighter is trying to make 50,000 lumen lights"; "Indiegogo campaign for Brighter, a very bright lamp". It most often appears alongside California, China, Twitter.

Article page
Brighter
Mention count
2
Issue count
2
First seen
December 01, 2023
Last seen
February 27, 2025
December 01, 2023 · Original source
45: I’ve written before about how most light boxes for seasonal affective disorder are much dimmer than the sun and would probably work better if they were brighter. A company called Brighter is trying to make 50,000 lumen lights, about 5x better than existing light boxes. They report that they’re looking for funding to start a Kickstarter campaign (apparently you need funding to start Kickstarters now?); you can reach the founder here if you’re interested.
February 27, 2025 · Original source
25: Indiegogo campaign for Brighter, a very bright lamp. Outdoors on a sunny day is 100,000 lux (a measure of brightness), indoors with an average lamp is only 50 lux. Some people think bringing the indoor number closer to the outdoor number should help with mood and energy, and there are preliminary good results for seasonal depression (even clinical seasonal depression lamps fall far short of outdoor brightness). The Brighter lamp is 50,000 lumen - lumens are a different measure from lux, of lamp power rather than brightness, but if you’re 5 feet away from the light then 50,000 lumen = 3,000 lux, which is getting a lot better. My only concern is that the light costs about $1,000; you should be able to do better with corn bulbs, but Brighter claims to have less eye strain, less glare, better color temperature, etc (I don’t know anything about these). People with treatment refractory SAD should be trying something like this, though it doesn’t have to be exactly this product - for details, see my writeup.
budesonide

budesonide is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 22, 2021 and December 22, 2021. The archive places it in contexts such as "fluvoxamine and budesonide are both appropriate to prescribe". It most often appears alongside FDA, fluvoxamine, Luvox.

Article page
budesonide
Mention count
2
Issue count
2
First seen
December 22, 2021
Last seen
December 22, 2021
December 22, 2021 · Original source
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
December 22, 2021 · Original source
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
Bugatti

Bugatti is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 30, 2024 and August 08, 2024. The archive places it in contexts such as "I’m strong and successful and own a Bugatti"; "constantly posted about he was better than them because of his Bugatti"; "I'm better than you because I own a Bugatti". It most often appears alongside 4chan, Achilles, Agamemnon.

Article page
Bugatti
Mention count
2
Issue count
2
First seen
July 30, 2024
Last seen
August 08, 2024
July 30, 2024 · Original source
If you Google “why aren’t there world’s fairs?” you get a link to this podcast, which explains that they had “useless gizmos”, that the towers were “unattractive”, and that it involved “a dismal thread of racism”. Also because “technology won’t save us”. I agree that this doesn’t literally say the words “we hate all life” - you either see it or you don’t. Parts of this vibe shift still confuse me, but the zoomed-out version seems clear enough. The old pro-embiggening world was complicit in moral catastrophes - racism, colonialism, the Holocaust, the destruction of much of the natural world. At some point these atrocities caught up to and outpaced its very real accomplishments, and society stopped being proud of itself and shifted to a harm-reduction approach. Nobody comes out and says outright that harm reduction necessarily has to mean doing as little as possible and trying to make yourself smaller and less impressive and sadder and uglier until you curl up into a tiny point and disappear. But “slave morality” and “master morality” are attractors; if you select too hard for part of one, you end up with the whole package. VI. Andrew Tate I originally wanted to explain to Bentham’s Bulldog why slave morality wasn’t obviously “the good one” and master morality “the bad one”. Lest I come down too hard and get you thinking that master morality is obviously “the good one”, let’s talk about Andrew Tate. In case you’ve been under a rock your whole life, Andrew Tate is a masculinity influencer. He’s a former world champion kickboxer who pivoted to self-help, sold scammy courses on business and relationships, and got rich. Some of his courses apparently recommended beating up women (I’m not sure if this was supposed to help your business or your relationship), and when people confronted him on this, his response was always “I’m strong and successful and own a Bugatti, which makes me better than you, you pathetic weakling failure”. He was credibly accused of rape (by “credibly” I mean that he sent one of the victims a text message saying “I love raping you”) and when people tried to cancel him over this, his response was always “I’m strong and successful and own a Bugatti, which makes me better than you, you pathetic weakling failure.” Finally he was indicted on one billion counts of sexual assault, human trafficking, and being a general scumbag of a human being; he is currently awaiting trial. Tate has, in some sense, many good qualities. He’s strong, athletic, and motivated. He earned tens of millions of dollars through hustle and hard work. He’s charismatic and compelling and, before his arrest, was one of the Internet’s most iconic influencers. I think master morality has to approve of all these things. Still, he’s obviously a jerk. This is exactly the situation that Nietzsche believes slave morality evolved for - letting me feel contempt for someone who’s stronger and richer and more successful than I am - and yup, now that I’m in this situation, I find myself definitely interested in a moral system that lets me do this. The obvious compromise goes something like: We can genuinely appreciate that Andrew Tate has the many good qualities listed above.
Therefore, we can feel contempt for him. I don’t have anything better than this obvious compromise, but I’m not satisfied by it. I would like to end up with an overall negative view of Tate. And if I do a simple calculation, (virtues - vices), then it seems like if his nonmoral virtues were strong enough, they could overcome the moral vices. If Tate was a really really good kickboxer, he might still end up in the black. It seems much more intuitive to say that no amount of nonmoral virtues can make up for his moral vices. But now we’re back at the full slave moralist package again! Some “compromise”! Also, suppose Tate wasn’t a rapist, he was just some kickboxing champion who was a jerk to people online and constantly posted about he was better than them because of his Bugatti. I still want to feel contempt for him! Now we have to rate the vice of “boastfulness” so negatively that it overwhelms all possible positive virtues, which sounds like some kind of ridiculous straw man of slave morality. All these problems would go away if we gave up on unified assessments of people. Then we could classify Tate as a very good kickboxer who also happens to rape a lot of people. But if we give up on unified assessments, aren’t we giving up on the very possibility of heroes? Isn’t this just the slave moralist denial of judgment? Also, I think Nietzsche would say something something vitalism. He seemed to think there was a coherent conceptual unity between being strong, being skilled, and being some sort of unconstrained wild person who didn’t care what lesser people thought. Is there some sense in which Andrew Tate loses some genuinely valuable virtue, however small, if he becomes a normal civilized person who says please and thank you and is really respectful to everyone? Does he become less powerful, in some sense where powerfulness is good? Is he less able to achieve his destiny of being glorious? I’m genuinely unsure what Nietzsche would have thought of Tate, but it probably isn’t something as simple as “he should be nicer”.4 I’m worried this still isn’t coming off strongly enough. You can argue “master morality is about being strong and good; slave morality is just about preserving your pathetic little feelings”. But most of life is people’s pathetic little feelings. People have proven over and over again that their decisions - about what to do, what to buy, who to vote for, even what to die for - depend more on what lets them feel dignity and self-respect than on any purely material considerations. Every so often, usually on 4chan, you see an actual bully really going at it, unrestrained. Some kind of shock jock, saying “Note to unattached liberal women above 40: you are ugly hags who have lost your chance with men and all your eggs have dried up and nobody will ever value you anymore, you should either beg for some fat alcoholic guy to take you in since that’s the only man you can get, or resign yourself to being a cat lady growing old with nothing to do but dwell on your regrets and what could have been.” Outside of 4chan, there’s a sort of universal alliance against these people, which the rest of us join immediately and unconsciously. Is this the dreaded “herd” of “slave morality”? If so, long live the herd. VII. Cotton Mather Fine. Maybe we do need a Superman to sort this out. What are our options? Preliminary question: where do the Puritans fall on this dichotomy? On the one hand, they’re Christian, so they have a strong slave morality heritage. They talked a lot about humility, altruism, frugality, and self-discipline. On the other, they sure did talk about them a lot. The Puritans were convinced that virtues were real and good. They were convinced that some people had more of them than others, and that made those people better. The Puritans would have burnt you at the stake if you accused them of believing in the Promethean human spirit conquering the natural world. But they did sort of believe in it - at least enough to believe it was their moral mission to colonize a virgin continent. My goal here isn’t to explore the weird Puritan theology around who was a good person (nobody, we are all incredibly sinful, but God chooses to redeem some people through no virtue of their own, and then those people are genuinely better off and do fewer sins). Rather, I want to examine two different forms (levels?) of slave morality. In the first form, you replace the masters’ virtues with different virtues. But those virtues are still real. You can still embody them more or less well. This sort of creates a new hierarchy. The Puritans wouldn’t have respected a Bronze Age barbarian warlord. But they did respect the local minister. And the local minister was probably a smart, competent, disciplined, hard-working guy. From your respect for the local minister, you can rebuild civilization. Instead of obeying a warlord, you obey the minister, out of respect for the God and the values that he represents. In the second form, you notice that the first form is just another hierarchy of masters. You (the wretched of the earth) used to be contemptible because you were weaker and poorer than the warlord. Now you’re contemptible because you’re less virtuous and disciplined than the minister. Even if there’s no local minister, everyone’s still keeping track of how you said the word “darn” once and are therefore unsuitable for God’s kingdom. So you decide to reject not just the masterly virtues (strength, wealth, etc), but also the slavish virtues (continence, dignity, altruism) in favor of . . . no virtues? The virtue of hating other virtues, which shows that you’re enlightened to the true nature of the world where all virtues are fake? I used to have this map on my wall: It’s Progressive-era propaganda about the superiority of the American North over the South, but I find it most interesting for its list of virtues. It starts with Liberty, then moves on to Free Speech, Intelligence, Obedience To Law, Knowledge, Equal Rights, Free Schools, Contentment, Love Of Country, Philanthropy, Benevolence, Happiness, Patience, Charity, Faith, Hope, Joy, Industry, Sobriety, Morality, Justice, Virtue, Truth, Honor, Peace, Light, and Immortality. I appreciate the Progressive virtues because of how skew they are to most of the ethical systems I encounter. They’re not leftist (Love Of Country? Industry? Morality?) or rightist (Equal Rights? Free Schools?). They’re not Nietzschean master moralist (Philanthropy? Contentment? Benevolence?) or slave moralist (Industry? Knowledge? Honor?). They’re Christian-ish, but not hair-shirts-and-self-flagellation Christian or God-n-guns-megachurch Christian. They’re the kind of Christians who you can kind of tell are going to end up supporting eugenics in a few years. I think I would classify them as a first-form-slave-morality liberalism, whereas most of the liberalism you encounter these days drifted at least a little into the second form. I’m not 100% on Team Early 20th Century Progressive, but they give me hope that there are weird-yet-coherent groupings of virtues we haven’t even imagined. I feel the same way about some old Soviet posters: These are obviously left-wing, in the sense that they’re literal Communist propaganda. But to the modern eye there’s something off about them, something that makes you want to call them right-wing or even fascist. They’re bold and optimistic. Even though the commissars who commissioned them probably rejected some traditional or capitalist conception of virtue, they still firmly insist that there’s something sort of like virtue or power which is attainable and good. I think these are first-form posters, and that most modern leftism is second-form. I think if you had to group barbarian warlords, Puritans, Soviet communists, and modern leftists on a Nietzschean/geneaological/aesthetic axis, it would go: (Barbarian warlords) | (Puritans, Soviet communists) | (modern leftists) So one very weak compromise - hardly even a compromise, since it predates Nietzsche - is to try to stick with first-form slave morality, in the hopes that most of the problems come from the second. VIII. Ayn Rand “Is Ayn Rand a Nietzschean?”- the greatest thread in the history of forums, locked by a moderator after 12239 pages of heated debate. There’s a real answer here. Rand started out respecting, maybe even loving Nietzsche. She once said that: [Nietzsche’s] Thus Spake Zarathustra is my Bible. I can never commit suicide while I have it. …which maybe reveals more about her psychological situation than I expected from the answer to a “who’s your favorite philosopher” questionnaire. But later on she broke from him. It’s hard to figure out her exact position - she has a bad habit of treating anyone who disagrees with her in any tiny detail as the Antichrist, such that it’s hard to figure out whether she thinks of someone as a 99% fellow traveler or an arch-enemy. Still, there are substantial differences. Nietzsche is more chaotic - he expects the superior man to defy all external rules in favor of his own glorious destiny. But Rand is attached to rules - most of all the epistemic rules of Reason, but also the usual moral tenets like “don’t kill” and “don’t steal”. Nietzsche’s masters take the Ron Swanson approach to justifying their actions: …whereas Rand’s masters are prone to giving twenty-page-long arguments for why whatever they’re doing is the right choice according to Objectively Correct Moral Law. Rand’s approach has lots of advantages. The Nietzschean master, like Andrew Tate, is an awful guy to have around. It’s hard to fit him into a functioning civilization, except maybe an autocracy with him as autocrat. Nietzsche’s pitch is “hey excellent people, you should try to become this guy”, never “hey normal people, you should support my project of creating these guys, out of your own self-interest.” The latter wouldn’t pass the laugh test. Rand’s masters, while still probably very stressful to be around, have been tamed. They follow civilized rules of honesty and nonviolence - not, of course, because they’re too weak to defy them, but because following civilized rules is objectively the coolest thing of all. Instead of competing in battle and leaving a trail of bloody corpses, they compete in Capitalism and leave a trail of high-paying jobs and excellent consumer goods. They’re not doing to serve you - “I should serve the little guy” is slave moralist bulls**t. But, by coincidence, their excellent actions are doing you a service. They might only invent rocket ships to enact their Promethean conquest of nature and prove their own greatness. But you still get to ride in one. Rand also spares more of a thought (or at least an afterthought) for the little guy. Capitalism needs all types - even the company janitor genuinely contributes to whatever glorious accomplishments are going on, and deserves to feel good about themselves. She wants everyone to be the best, most ambitious, and most fighting-for-their-own-aesthetic/moral-vision they can be. But if that means being the company janitor, that’s fine. And if you love rockets and you consummate that love by becoming the janitor for a rocket company, the Objectively Correct Moral Law is 100% on board. I am not a Nietzsche scholar, but I think this is a more productive answer than Nietzsche has for this question. The disadvantage of Rand’s approach compared to Nietzsche’s is that it only works if you believe her proofs about why the Objectively Correct Moral Law is definitely objective and correct - most of which seem to me to be either hand-wavy or balderdash. Otherwise the whole thing breaks down - why is the most masterful thing to be a positive-sum capitalist instead of a negative-sum warlord? Rand really really wants to justify a peaceful, glorious, positive-sum society, to the exact people most capable of benefiting from defecting against it, without bringing in altruism or the common good at any point. It’s an extremely sympathetic goal. But I don’t think she makes it. Still, this is why I’m fond of her. If you really read her books - as opposed to skimming them while subvocalizing “this is that evil woman who loves selfishness” under your breath the whole time - it’s obvious that she believes, with a deep and burning belief, that good things are good. She really really wants to think that you can objectively convince people to support a peaceful, glorious, positive-sum society, without any hint of the psychologically-toxic slave morality that typified the USSR she grew up in. When people react to her books with loathing - without even a hint of fondness - I get suspicious that they’ve gotten so deep into slave morality that thy can’t recognize goodness when it hits them over the head with a sledgehammer. Elsewhere, I wrote: Edward Teach (Sadly, Porn) is famous for making up fake novels to criticize, and it is a little known fact that the "Ayn Rand" character along with all her novels are 100% his work. They operate as a diagnostic test based on his psychodynamic theory of envy. The instrument presents a picture of some exceptional people achieving great things who don't apologize for their greatness, and doesn’t explicitly ask the patient - I mean, reader - for their opinion. If the reader has no strong opinion, or says something like "Good for them, I guess," she passes the test. "I like these people and will use them as a role model" also passes. Some specific criticisms (see below) may also pass. If the reader says "Ah, people who are better than the pathetic sheep around them, just like I'm better than all the pathetic sheep around me!", she . . . still passes the test. That's not what it's testing for! You fail the test if you absolutely freak out about some combination of the Rand characters themselves and the potential existence of arrogant people who identify with the Rand characters. The secret is that it's not a screening test for the kind of people who would get featured on /r/iamverysmart. It's a screening test for the kind of people who would comment on /r/iamverysmart, ie the self-designated Tall Poppy Police, ie the people who build their ego off being the enforcers of the rule that you're not allowed to look better than anyone else. These people's basic mental stance is to hate people who seem too excellent. They don't think of it in these terms. They think of it as calling out arrogance, although if you look too closely you'll find their definition of arrogance covers anyone who seems excellent and but doesn't spend all their time apologizing and abasing themselves and denying it. The brilliance of Teach-Rand is how he-she draws this tendency to the foreground For example, why the whole "Objectivism" thing? Not because value is necessarily completely objective, but because the idea that any value might ever be even partially objective freaks out the Tall Poppy Syndrome people. Mention value at all, and they say you must be trying to secretly smuggle in the assumption that you are more valuable than other people (and therefore you are less valuable than other people, and therefore they are better than you). The same is true of Reason. Mention that Reason exists, and they'll interpret it as a claim that you, the only rational person, are claiming to always be right and infallible. But (they retort) actually nobody knows anything, and the only wise people are the people like them who humbly admit this. (how do you decide what's true without Reason? By bias-based-reasoning - "You say X, but I can imagine a way that would come from a place of believing you're better than other people, therefore, Not-X is true. You say that's a logical fallacy? That must come from a place of believing you're smarter than everyone else and the only person who can use Facts and Logic.") The Teach-Rand test is designed to catch the sort of person who, if someone says that on a right triangle a^2 + b^2 = c^2, responds with "Oh, so you're claiming to be some kind of right triangle expert who's better than the rest of us? You really need to work on that arrogance problem! Super cringe!" Any criticism of the book that doesn't come from this particular place is irrelevant to the test and doesn't count against your grade. (which is good, because the books are bad in a lot of ways. But that's fine - Rorschach blots don't also have to be great art!) Still, I don’t think she’s the superman (superwoman?) who successfully transcends the dichotomy Her philosophy is only as strong as its proofs of Objective Correctness, which I consider weak. Without those, you need some subjective motivation to glue things together - of which altruism is the most popular. But also, don’t we like altruism? When we’re bestriding the Earth like colossi, working on our glorious rocket ships to colonize the universe, isn’t part of what we’re thinking “this is going to revolutionize humankind and make everybody better off?” If you force yourself to reject that motivation, to just repeat “no no no, I’m only doing this because rockets are really big and make cool explosions”, aren’t you cutting out a part of yourself, in exactly the way Nietzschean masters are supposed to try to avoid doing? I find something very compelling about Rand. I think she goes some of the way to answering the Andrew Tate objection to master morality. But she’s a means and not an end. A real superman would have to figure out some way to reintroduce basic human kindness. IX. Matt Yglesias Yglesias’s mantra - “good things are good” - is too perfect and profound to come from anyone other than an esoteric master of Nietzschean philosophy. Good Straussians ignore the title and focus on the subtitle. Nietzsche wrote in the 1890s. There were still real nobles and emperors walking around; communists had not yet started calling capitalism “late capitalism”. Sure, his world was probably some sort of weak compromise between master and slave morality, but it was different from our weak compromise. Our weak compromise was forged through dialogue and warfare with fascism’s novel take on master morality and socialism’s novel take on slave morality. I think of Yglesias - who combines an insistence that good things are good and a proclivity for embiggenment with commitments to democracy, the welfare state, and the poorest among us - as one of its most self-conscious proponents. When I first titled this post, I didn’t know that Richard Hanania had come to the same conclusion and created this face-mash-up of Matt Yglesias and Nietzsche. The compromise goes something like: Everyone is equal before the law, before the metaphorical throne of metaphorical God, and in some poorly defined philosophical sense. This is very important. It’s our headline result. Everything else should be interpreted in light of this central fact.
August 08, 2024 · Original source
The relationship between the "masters" and the "slaves" can be straightforwardly literal, but fundamentally, the masters don't need to rule over any slaves; what they are a master over is their own self. They don't need to "lord it over" anyone; if you have to tell people "I'm better than you because I own a Bugatti," you are their slave, your feelings are enslaved to the approval/respect/recognition of the people who are putatively "beneath" you. From Twilight of the Idols:
Burger King

Burger King is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 10, 2021 and February 16, 2022. The archive places it in contexts such as "basic protection borne out of the sheer size and visibility of corporations like Burger King"; "Burger King: “Have It Your Way”". It most often appears alongside 1984, Abercrombie & Fitch, American.

Article page
Burger King
Mention count
2
Issue count
2
First seen
June 10, 2021
Last seen
February 16, 2022
June 10, 2021 · Original source
I see Orwell’s dream as having come true in a limited sense. Upscale restaraunts that serve terrible food made by people working for pennies are relatively rare now( except on cruise ships). Their two primary aspects (hellish working conditions and bad food)have split and diverged and now exist in different food industry niches: on the one hand we have the modern fast food restaraunt, where the work is “done with simple efficiency…[scullions] might work six of eight hours a day” and true mid-to-upscale restaraunts, where a higher level of cleanliness and quality in preperation and ingredients is assumed, and I think in most cases, delivered upon. In these sorts of places, which Bourdain describes in Kitchen Confidential, the chefs work in hellish conditions, but are paid relatively well and work more reasonable, if irregular and nocturnal, hours. In fast food places, people are paid less but are subject to a form of basic protection borne out of the sheer size and visibility of corporations like Burger King and McDonalds. No doubt Orwell would find this situation ghastly in it’s own way, but I doubt he’d deny the life of restaraunt and hotel workers has markedly improved since the 1920s. Trouble is, Orwell doesn’t see these horrible working conditions are merely a result of people’s misguided desire to eat overpriced, low-quality food:
February 16, 2022 · Original source
As for you, you’re probably even more contemptible than these Athenians. Teach thinks the modern psyche is downstream of decisions by advertising agencies. At some point their usual trick of selling products through implied peer pressure and hot women stopped paying as many dividends. The companies did some kind of judo move where they told us “well, darn, you’re just too individual and unique a person to fall for a mass advertising campaign - and incidentally the surest way to make everyone understand that is to drink Coca-Cola, The Drink For Individual Unique People”. And everyone lapped it up. This isn’t even subtle, the highest market value company in the world uses the motto “Think Different”. Or Burger King: “Have It Your Way”. Literal actual Coke printed the 150 most popular names onto their bottles in the hopes you would see your name and think you had a special relationship with them.
Cadillac

Cadillac is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 13, 2022 and June 12, 2024. The archive places it in contexts such as "His vehicle of choice was a Cadillac"; "a Yugo is inferior to a Cadillac". It most often appears alongside 1890s, @VividVoid_, Alan Turing.

Article page
Cadillac
Mention count
2
Issue count
2
First seen
July 13, 2022
Last seen
June 12, 2024
July 13, 2022 · Original source
Von Neumann loved driving very much but had never passed a test. At [his wife] Mariette’s suggestion, he bribed a driving examiner. This did nothing to improve his driving. He sped along crowded roads as if they were many-body problems to be negotiated by calculating the best route through on the fly. He often failed, and an intersection in Princeton was soon christened “Von Neumann Corner” on account of the many accidents he had there. Bored on open roads, he slowed down. When conversation faltered, he would sing; swaying and rocking the streeting wheel from side to side with him. The couple would buy a new car every year, usually because von Neumann had totalled the previous one. His vehicle of choice was a Cadillac, ‘because’, he explained ‘no one would sell me a tank’. Miraculously, he escaped largely unscathed from these smash-ups, often returning with the unlikeliest of explanations. "I was proceeding down the road,” begins one fabulous excuse. “The trees on the right were passing me in orderly fashion at 60 miles an hour. Suddenly one of them stepped in my path. Boom!”
June 12, 2024 · Original source
(Some people will object that nobody is “genetically inferior”, because “inferior” means “worse in every possible way”, and nobody is worse in all ways - maybe the person with cystic fibrosis has a gene for great memory or something. But first of all, if we come up with a contrived example where this isn’t true - eg identical twins who have exactly the same genes, except one has a somatic mutation causing cystic fibrosis - I’m still reluctant to say the mutated twin is “genetically inferior”. And second of all, this isn’t how we use the word “inferior” anywhere else - we might say that eg a Yugo is inferior to a Cadillac, even if the Yugo is better on some trivial dimension like having a slightly longer tire life.)
Chick-Fil-A

Chick-Fil-A is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 25, 2021 and March 09, 2023. The archive places it in contexts such as "won't even speak the name Chick-Fil-A"; "consider eating at Chick-Fil-A". It most often appears alongside Akron, Amherst, Asian Community Center.

Article page
Chick-Fil-A
Mention count
2
Issue count
2
First seen
February 25, 2021
Last seen
March 09, 2023
February 25, 2021 · Original source
Trump stood against the upper class. He might define them as: people who live in nice apartments in Manhattan or SF or DC and laugh under their breath if anybody comes from Akron or Tampa. Who eat Thai food and Ethiopian food and anything fusion, think they would gain 200 lbs if they ever stepped in a McDonalds, and won't even speak the name Chick-Fil-A. Who usually go to Ivy League colleges, though Amherst or Berkeley is acceptable if absolutely necessary. Who conspicuously love Broadway (especially Hamilton), LGBT, education, "expertise", mass transit, and foreign anything. They conspicuously hate NASCAR, wrestling, football, "fast food", SUVs, FOX, guns, the South, evangelicals, and reality TV. Who would never get married before age 25 and have cutesy pins about how cats are better than children. Who get jobs in journalism, academia, government, consulting, or anything else with no time-card where you never have to use your hands. Who all have exactly the same political and aesthetic opinions on everything, and think the noblest and most important task imaginable is to gatekeep information in ways that force everyone else to share those opinions too.
March 09, 2023 · Original source
Actions can be hyperstitious slurs; consider eating at Chick-Fil-A. If enough people who care about gay rights boycott them, then eating there actively signals that you’re defecting from the boycott and must not care about gay rights very much. On the other hand, if only a small fraction of people who care about gay rights boycott it, then eating there doesn’t signal anything and it’s fine. If anyone ever credibly said “eating at Chick-Fil-A is a strong defection from the gay rights cause” and everyone believed them, there would be a stable equilibrium where nobody who cared about gay rights ate at Chick-Fil-A. But as long as people don’t believe that, it’s fine.
Chrome

Chrome is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 28, 2021 and October 09, 2023. The archive places it in contexts such as "Available for Firefox and Chrome"; "there’s also a Chrome extension version". It most often appears alongside India, Academic Decathlon, ACX Grants.

Article page
Chrome
Mention count
2
Issue count
2
First seen
February 28, 2021
Last seen
October 09, 2023
February 28, 2021 · Original source
5: Substack still claims to be working on fixing some of the comment problems on their end, though I don’t have an ETA or progress reports to give you. While you’re waiting, ACX reader Pycea has created a browser extension which fixes some remaining issues with the comments section here, including auto-expanding everything, highlighting new comments, hiding hearts, and several other things. Available for Firefox and Chrome, with some partial fixes for Safari available here. Thanks, Pycea!
October 09, 2023 · Original source
Judges agreed this was a well-made app that addressed a real need (there’s also a Chrome extension version). We would have evaluated it higher, except that’s for a play-money betting site with limited user base, and so far it hasn’t gotten much traction. I’m hoping that highlighting it here changes that. And Austin has mentioned the possibility of integrating it with Manifold itself at some point.
Claude Code

Claude Code is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 13, 2026 and April 06, 2026. The archive places it in contexts such as "You extract proper noun references and culturally relevant entities from a lifestyle/culture newsletter"; "fluency in AI coding tools (Claude Code, Cursor)". It most often appears alongside OpenAI, ACX, Adeline.

Article page
Claude Code
Mention count
2
Issue count
2
First seen
January 13, 2026
Last seen
April 06, 2026
January 13, 2026 · Original source
“Yeah, usually I’m working late. But that was the bad old days, before Claude Code! Now Claude works, and I party!”
“Is everyone here letting Claude Code do their work for them?”
Lucy joins the conversation. “I fired all my startup’s employees and replaced them with seventy-four Claude Code instances. Then I replaced myself with a Claude Code that monitors if the other Claude Codes are doing a good job, and, if not, fires them and replaces them with even more Claude Codes. Profits are up 20% since last month, according to my accountant’s Claude Code.”
April 06, 2026 · Original source
Spartacus.app is urgently seeking a freelance TypeScript/Next.js/Supabase developer. Spartacus is a live platform for conditional-commitment collective action, with successful pilots involving unions and AI safety organizations. Our primary developer departed unexpectedly, and we need someone to pick up active development immediately. This is a remote, project-based contract with negotiable compensation plus possible revenue sharing (tools reimbursed). Strong TypeScript/Next.js/Supabase skills, along with fluency in AI coding tools (Claude Code, Cursor), are required. Detailed role requirements here. Reach out to jordan@spartacus.app
Coinbase

Coinbase is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 22, 2021 and July 23, 2024. The archive places it in contexts such as "My level of crypto knowledge is “can use Coinbase”"; "businesspeople should encourage their companies to become mission-focused in the style of Coinbase". It most often appears alongside Democrats, Afghanistan, Akhenaten.

Article page
Coinbase
Mention count
2
Issue count
2
First seen
June 22, 2021
Last seen
July 23, 2024
June 22, 2021 · Original source
Will crypto sites default before 2023? Bitmex 26%, Binance 15%, Coinbase 5% Not many predictions here, so don’t take these numbers too seriously. I also don’t know what a “default” would mean in this sense - default to at least one customer, but everyone else is okay? Lose all its money to a hack?
I’m happy to report that getting money into Polymarket has gone from impossible to merely annoying. Non-Americans can apparently do it directly with a credit card; Americans will have to send USDC, separately send Ethereum to a different address to cover transaction fees, then wait ~10 minutes for everything to percolate through. My level of crypto knowledge is “can use Coinbase” and I was able to figure it out. There’s also apparently an easier way with a Metamask wallet, which I didn’t try.
July 23, 2024 · Original source
Academics should encourage their schools to adopt the Chicago Principles, and businesspeople should encourage their companies to become mission-focused in the style of Coinbase. Ideally these commitments would have legal force, letting students/stockholders sue for violations. Politicians should incentivize the institutions they influence (eg state universities, government contractors) to do this.
Concerta

Concerta is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 25, 2021 and July 06, 2022. The archive places it in contexts such as "Next I switched to Concerta, which worked, but increased my anxiety"; "half the kids got Concerta (ie long-acting Ritalin)". It most often appears alongside Ritalin, Adderall, ADHD.

Article page
Concerta
Mention count
2
Issue count
2
First seen
January 25, 2021
Last seen
July 06, 2022
January 25, 2021 · Original source
How is this not more widely prescribed? My doc had me on Strattera at first, didn't help at all. Next I switched to Concerta, which worked, but increased my anxiety, and I had a crash. Next I switched to Adderall, which had almost the same effect as Concerta but on top of that I had no appetite. Finally I switched to Desoxyn and that's when my life started to turn around. My grades instantly went up and homework became fun for me. Math problems became like a puzzle, and history became fun, like watching a real-life movie. Right when I made the switch to Desoxyn, I got caught up on ALL my homework and my grades instantly switched from D's and F's to B's and A's. Not only that, but my social anxiety was completely GONE.
July 06, 2022 · Original source
173 kids, mostly Hispanic boys age 7-12, were in a “therapeutic ADHD summer camp” intended to help them learn focusing and attention-directing techniques (style tip: do not call this a “concentration camp”). The kids had two short classes each day, one on vocabulary and one on a grab bag of different subject matters. For the first three weeks, half the kids got Concerta (ie long-acting Ritalin) and the other half didn’t, then they switched for the next three weeks. As an additional test, there was a ten minute period each day when the kids were asked to do math problems as fast as possible. Here are the results:
“OROS-MPH” is Martian for Concerta. The bottom left graph is how many math problems kids completed per minute. Kids on Concerta do math about 50% faster, and this difference is significant. Bottom right is number of classroom rule violations per hour. Kids on Concerta only cause trouble about half as often, and this is significant too. So the Concerta’s clearly doing something, and I think it would be fair to describe that thing as “making kids pay more attention”.
The bottom left graph is how many math problems kids completed per minute. Kids on Concerta do math about 50% faster, and this difference is significant. Bottom right is number of classroom rule violations per hour. Kids on Concerta only cause trouble about half as often, and this is significant too. So the Concerta’s clearly doing something, and I think it would be fair to describe that thing as “making kids pay more attention”.
Cursor

Cursor is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 26, 2025 and April 06, 2026. The archive places it in contexts such as "AI-enabled software applications like Cursor"; "fluency in AI coding tools (Claude Code, Cursor)". It most often appears alongside Anthropic, OpenAI, 9/11.

Article page
Cursor
Mention count
2
Issue count
2
First seen
November 26, 2025
Last seen
April 06, 2026
November 26, 2025 · Original source
Especially in hardware applications. The US has a good software ecosystem, and more advanced models might let us keep an edge in AI-enabled software applications like Cursor.
April 06, 2026 · Original source
Spartacus.app is urgently seeking a freelance TypeScript/Next.js/Supabase developer. Spartacus is a live platform for conditional-commitment collective action, with successful pilots involving unions and AI safety organizations. Our primary developer departed unexpectedly, and we need someone to pick up active development immediately. This is a remote, project-based contract with negotiable compensation plus possible revenue sharing (tools reimbursed). Strong TypeScript/Next.js/Supabase skills, along with fluency in AI coding tools (Claude Code, Cursor), are required. Detailed role requirements here. Reach out to jordan@spartacus.app
Deplin

Deplin is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 12, 2021 and May 25, 2021. The archive places it in contexts such as "Nor is there much difference between regular methylfolate and prescription Deplin"; "The FDA-approved version is called Deplin , and is prescription-only and more expensive". It most often appears alongside FDA, US, 2002 meta-analysis by Cochrane Collaboration.

Article page
Deplin
Mention count
2
Issue count
2
First seen
May 12, 2021
Last seen
May 25, 2021
May 12, 2021 · Original source
Maybe you’ve read my old post on Lovaza? Lovaza is prescription fish oil. You can get non-prescription fish oil from any supermarket or supplement store for $10 per Giant Jar. Or, if you prefer, you can go to a doctor and get prescribed Lovaza for $300 a month. Is there a difference between Lovaza and regular fish oil? Other than the 30x markup and prescription-gating, no. Nor is there much difference between regular methylfolate and prescription Deplin. You can get some effective treatment for very cheap as a supplement. Or you can get the same treatment for much more money as a prescription medication.
May 25, 2021 · Original source
L-methylfolate is a form of folic acid, aka Vitamin B9, common in various vegetables. It’s part of various important chemical processes in the body, including the synthesis of serotonin, and various studies support its use in depression. Some people will try to claim that a gene called MTHFR is very relevant here, but I disagree with this and will have a page up about it eventually – the summary is that you should consider using l-methylfolate regardless of what allele of MTHFR you have. I’ve listed this supplement first because it’s the only one which has been officially approved by the FDA as safe and effective for depression. The FDA-approved version is called Deplin, and is prescription-only and more expensive, but it’s chemically identical to regular l-methylfolate which you can buy without a prescription in stores. Be careful as many stores will sell 1 mg tablets, but the recommended dose is 7.5 – 15 mg daily. You can get l-methylfolate 15 mg here.
Disney

Disney is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 14, 2023 and January 29, 2025. The archive places it in contexts such as "Disney-esque sentimentality is the exact emotional equivalent to intellectual contempt"; "leading to finding Disney-magic love a few months later". It most often appears alongside !Kung San, aboriginal people on the west coast of Canada, Adam Smith.

Article page
Disney
Mention count
2
Issue count
2
First seen
July 14, 2023
Last seen
January 29, 2025
July 14, 2023 · Original source
From trivial to rich: the trick What could an intellectually rich elementary school curriculum look like, if we built it on kids’ cognitive strengths? He gives us one suggestion to help us do this: ask where each discipline came from in the first place. What was math before it was math, for example — or science before it was science? Q: How on Earth could that help? That’ll become clear later, when we finally uncover what Egan thinks “education” actually is, and see what job he wants us to give schools. For now, take it as a tantalizing hint… or, y’know, just ignore it. Elementary literature & language What was literature before it was literature? Before people invented writing, they had rich oral traditions: they told simple stories, recited poems, and shared proverbs. Egan suggests that these bits of oral tradition should form the backbone of the elementary literature curriculum. Q: What sorts of stories? As many as we can, and from as many diverse cultures as possible! Folktales are wonderful, as are myths. Think the Aboriginal story of “The Rainbow Serpent”, episodes from the Sumerian “Epic of Gilgamesh”, the Egyptian story of Osiris & Isis, the Greek story of Orpheus & Eurydice, the Chinese Legend of the White Snake, the Japanese Tale of Amaterasu and Susanoo, the Ashanti tales of Anansi, the Aztec myth of Quetzalcoatl, the English legend of King Arthur, the Maori myth of Maui and the Sun, the Roman story of Romulus and Remus, selections from the Indian Mahabharata, the Anglo-Saxon epic of Beowulf, the Inca legend of the Sun and Moon, the Iroquois Myth of the Flying Head (a real thing! look it up!), and the Ojibwe story of Turtle Island. Q: That was a lot of examples. Are you going to keep giving so many? I’ve got a [mumble mumble mumble] to get to. Sorry about that. Sometimes, though, I feel that a limitation of reading Educated Mind is that, in trying to keep his book to a manageable size, Egan skimped on examples in some places that it matters. It’s easy to read his occasional example and assume he intends that it hold some central place in the curriculum — when all he wants to do is display how rich and diverse the curriculum could be. (Also: good God, I didn’t even include an example from Norse mythology!) So from now on, just assume that every category could be filled with oodles of examples. Q: What sorts of poems? Lots of poems, first of all. We shouldn’t steer toward “fancy” poems — rather, we should find poems that appeal to kids immediately — think Shel Silverstein, Mother Goose, Dr. Seuss, Jack Prelutsky, Edward Lear, or Ogden Nash… that sort of thing. In a biting essay, Egan suggests these poets like these appeal to kids precisely because they leverage kids’ cognitive strengths: “we should find, and encourage saying and singing and shouting aloud verse with strong narrative forms, thumping rhymes and rhythms, the most vivid images, fun with metaphors, and a rollicking story.” Q: Why proverbs? Proverbs stick in your mind almost effortlessly. (“All’s fair in love and war!” “When in Rome, do as the Romans do!” “You can’t judge a book by its cover!”) They’re also useful; they capture general truths. Kids can apply them to all sorts of situations, but also discuss them — to what extent are they wise or foolish? (I remember my surprise when I realized that they couldn’t all be true — because you can’t follow “look before you leap” and “he who hesitates is lost” at the same time! I’m embarrassed to say that I think I only realized this when I was in college.) Elementary science What was science before it was science? Egan suggests: being immersed in the natural world. We might, he writes, encourage elementary students to “adopt” some feature of the natural world — a patch of grass, a cat, a branch, a stream — and simply observe it at length. To do this, we can use the cognitive strength of reverie. Q: Oh, do you mean like kids sometimes do in science class nowadays — describe a thing to a partner, make notes, draw it, and label its parts? No, the exact opposite! That’s all about squeezing the experience into words and forms that we understand. What we want “is less an attempt to know about nature as to know it in some participatory way, to know it as something we are an intimate part of, not set off from”. Q: That sounds a little… “woo” to me. It did to me, too… until I remembered my childhood climbing tree. I didn’t much like to go outside as a child, but I had this one tree that I’d climb up and read for hours and hours. If I close my eyes I can bring to mind the precise texture of its bark, the roughness of its broken-off branches, the coolness of its leaves, the always-surprising solidness of its trunk… I’m bigger now, but I think if I were back in my parent’s yard, I could still navigate its limbs with my eyes closed. I have, at this point in my life, read a fair number of books about trees, but I’d be surprised if all of them together more than equaled the amount I learned from that tree — my tree. Elementary math What was math before it was math? Egan suggests: counting and logic. We might, then, use rhythms, metaphors, stories, and jokes to help kids become fond of these. Q: Counting is pretty… basic. Could it really be improved? Beware of “the curse of knowledge”: Steven Pinker’s phrase for forgetting that something was once difficult! Egan suggests we should spend time helping kids count wonderfully. We can start early with counting rhymes. (“One, two, buckle my shoe! Three, four, out the door! Five, six…”) But we can also help kids use their fingers as metaphors. There are some pretty cool ways of using your hands as an abacus — and did you know that you can count up to 1,023 using just your fingers on both hands, and a knowledge of binary? Q: Logic — I’m intrigued! Aristotelian, or Boolean? Neither, for the time being — Piaget was presumably onto something when he found that young children couldn’t reason abstractly, but he was looking at logic in a vacuum. When we put logic into the context of stories, we find that kids can deal with logic just fine. There’s an entire worldwide network of educators, in fact, called Philosophy for Children, who have written whole books about how to do this, and Egan loves it all. Sometimes they read stories and ask simple questions: “What is friendship?” or “What does it mean to be brave?” They also pose ethical questions: “Is it ever right to spill a secret?” And they pose paradoxes: “Can you step in the same river twice?” Q: You mentioned “jokes” a moment ago. Care to elaborate? Egan thinks that, to help kids get good at math, you should tell kids jokes. Q: That’s… new. I think so, too — but he backs it up pretty well. To be funny, jokes (or at least most kid jokes) rely on a leap in logic: Why can’t you trust an atom? They make up everything. Knock-knock. Who’s there? Boo. Boo-hoo? Don’t cry, it’s just a joke! To understand the joke, kids have to follow the logic — spotting patterns, making connections, and tracking what their audience expects a word to mean. That’s a lot of cognitive lifting. And Egan goes further, suggesting that we grit our teeth and create methods to help kids invent their own jokes, no matter how horrible they’ll be at first. (The things we do for learning…) Q: Wait wait wait! What about addition facts, and multiplication tables, and fractions? Egan emphasizes that his methods are designed to be add-ons to the standard math curriculum. In general, he’s a don’t-blow-up-the-system sort of guy, and if something seems especially weird, you should probably assume it’s an add-on to the regular curriculum rather than a replacement, even if I forget to say so. Elementary arts What was art before it was art? Egan suggests we pop our heads into Paleolithic caves for our inspiration. Whatever the specific meaning of all those charcoal elk and aurochs and mammoths (communication with the spirit world? art for art’s sake? a way to impress babes?), Egan thinks it obvious that they were also an attempt to capture an intense experience that would be difficult to express in words alone. What did it feel like to be near an aurochs, or a saber-toothed tiger? “The arts help us,” Egan writes, “to hear and see afresh, to force our perceptions and sensations to experience again the immediacy and vividness of the world”. If we follow this, then, we don’t want to help kids build “art skills” so they can draw like an adult — rather, we want to help them amass a repository of diverse aesthetic feelings that they’ll want to express. We should provide them with a riot of experiences. Q: That couldn’t be more opaque. Examples, please! Egan writes that we should have children learn to whistle, sing, and click their tongue; we should help them emulate the ways a skunk or a hawk or a stick bug might move through a space. We should expose them to scores of different temperatures and materials. In music, we should help them love Beethoven, yes, but also the Beatles; Tchaikovsky, yes, but also Tuvan throat singers, and also John Cage, whale song, and bird song. Q: That’s a lot of experiences, but what would they be doing? An interesting aspect of Egan’s view of education is that he doesn’t seem to think we should push kids right to the “doing” phase. He wants to help kids cultivate an affective relationship with the world. In any case, he writes that as students get more experienced, we should prompt them to move from merely enjoying these experiences to trying to systematically shape similar experiences. And drawing, painting, and playing music could easily be folded into other parts of the curriculum. Elementary social studies What was social studies before it was social studies? Well. Remember how, just a moment ago, I wrote that you could assume that you should probably assume that Kieran isn’t in favor of junking the curriculum as it currently stands? He suggests we very carefully pick up the elementary social studies curriculum, place it into a trash can, and set the whole mess on fire. He isn’t worried about much of importance being lost. (Remember that the “expanding horizons” model is, to him, the original sin of 20th century educational reform, and he repeatedly quotes student surveys showing that “social studies” regularly wins the title of “most boring subject”.) In its place, he suggests we put history — which, he hints, we should think of as the centerpiece of the elementary curriculum. So the real question is what was history before it was history? His answer, surprisingly, is myth. Q: Egan wants us to teach myths as if they were history? Not at all. What he suggests, though, is that we look at how myths operate as narratives — so we can design an intellectually vivid history curriculum. And myths really are special: each is built on at least one binary (like weak vs. strong, or lies vs. truth, or so on), and uses that to tell the story of the big picture of the world. They’re so powerful that people can understand it, remember it, and love it — even if that thing never happened. We should take that power, Egan says, and apply it to things that really did happen. Q: So what history does he think kids should learn in elementary school? The great struggles of humanity from across the whole. Flippin’. World. We’re still talking about young children, so these should be done as simple stories. The goal isn’t to make them history PhD’s, so we needn’t even try to put them in any sort of order. Egan suggests that, in first grade, we pick a single binary like “freedom against oppression” and tell kids a welter of stories, again from as many cultures as possible, and as many times in history as possible. Q: Can you give examples? Oh, all right — in first grade we can tell kids the stories of the war of the Greek city-states against the Persian empire, and the slave uprising of Spartacus against the Romans. We can tell them about the plight of Jews in medieval Europe, and of the unsuccessful Sepoy Rebellion in India against the British. We can tell the stories of the American, French, and Haitian Revolutions, and about the Chinese Taiping Rebellion against the Qing Dynasty. We can tell them the story of the escaped slave Harriet Tubman returning to the South to rescue her kinsmen, the story of six-year-old Ruby Bridges facing threats to integrate her elementary school, and the story of how the Mau-Mau uprising led to modern-day Kenya. We can tell the stories of Mexican-American union organizer Cesar Chavez and of Malala Yousafzai surviving an assassination attempt to advocate for female literacy. The world does not lack for stories of oppression and liberation that can capture the attention of a six-year-old. Q: That’s… huh. What stories might they hear in second and third grade? Egan gives examples, but I won’t list them here. He suggests we use a similar approach for each, except that we swap out the binary each year. He thinks “the struggle for security against danger” would work well for year two, and “the struggle for knowledge against ignorance” would work well for year three. (That year could have a lot of overlap with the science curriculum.) Q: Anything else, for history? Yes — they should get a sense of Big History. They should get some simple stories about the ice age, the Cenozoic, the age of dinosaurs, the Paleozoic, the origins of our solar system, and the Big Bang. (Because if the ancient Norse can tell their story of the beginning of the universe, by gum, we can tell ours, too.) To sum up Egan argues that the problem of early schooling is that it’s trivial — and it’s trivial because the dominant theories of educational psychology see children as lesser versions of adults. What else would we teach them, except dumbed-down versions of what adults learn? But children have certain cognitive strengths that schools aren’t making systematic use of. If we rebuild elementary schools on those strengths, we could turn schooling upside down. We could stop seeing the curriculum as a bag of information to impart, and start seeing it as a set of great stories to tell — and invite kids into. Kids could experience (both intellectually and emotionally) the great struggles of humanity and see that they can join in them. Students could experience the story of education as the beginning of a very real adventure. Egan’s elementary school: some skeptical questions Q: I’m not sure I’m understanding what you mean by “mental images”. Care to explain? It’s an interesting fact of human cognition that just a few words can whip up a complex mental experience. Egan doesn’t just mean what we might call “visual imagery” — the ability to hold, say, the image of a bespectacled, spat-wearing duck in your mind without seeing a photograph. He’s also including what psychologists call auditory imagery, olfactory imagery, gustatory imagery, and tactile imagery. Q: How could all of that be helpful in schools? Humanity has a built-in VR system, and we’re not using it! Egan invites us to pretend we’re teaching a class about the humble earthworm. We might list off facts — “earthworms are so many centimeters long, move through soil by means of their something-or-other muscles…” but he suggests we can evoke images, say, “of what it would be like to slither and push through the soil, hesitantly exploring in one direction then another, looking for easier passages, contracting and expanding our sequence of muscles segment by segment, and sensing moisture, scents, grubs, or whatever”. Those facts are now felt by the student; the knowledge has become part of them. And just a few words can spark a complex mental experience, one going beyond literal images to include imagined sounds, smells, tastes, and more. These experiences can feel real and stick with us. (That these mental images are so easy to evoke, and so meaningfully felt, feels something like the proverbial hundred dollar bill on the ground.) Q: How could metaphors be helpful? It really is interesting that so much of the “constructivist” turn in psychology — that is, the notion that children don’t absorb knowledge, but construct it — has continued to focus on logics-mathematical reasoning, when there’s been mounting evidence for decades that metaphors are more central. It’s not just that we use metaphors to better understand things we already know, we also use them to grasp new knowledge. What’s more, psychologists have devised tests to measure the skill at metaphor-making, and have given them to people of different ages. What they found was that eleven-year-olds make more metaphors (and higher quality metaphors) than do undergraduates — and that four-year-olds have both groups beat. Again, hundred dollar bills on the sidewalk. Q: Your talk of “binaries” has me worried — binaries like good/evil and male/female are the source of so many of our most pernicious stereotypes! Isn’t the purpose of education to get us beyond stuff like this? Yes, it is! Education is supposed to complicate our understanding — but that means we’ve gotta start somewhere, and binaries provide us a natural starting place. As an uncontroversial example, think about temperature. We all begin as babies by perceiving two temperatures — hot and cold. Later, we add on intermediate categories — warm and cool. (Note that the human body is the assumed mid-point to temperature. Binaries often work like this; “big” and “small” mean “bigger or smaller than me”, “nasty” and “kind” mean “nastier or kinder than I am, except when my brother is really asking for it”, and so on.) A good story (and an Egan-inspired elementary curriculum is, in a sense, nothing but good stories) will go further, and transform the binary. Toy Story is grounded in the binary of abandonment/belonging: at the beginning, the toy cowboy Woody belongs to his owner, and has his affection. Then a rival comes who threatens his belonging. In trying to get back to belonging, Woody is entirely lost — and to save the day, he has to come to a deeper understanding of what belonging means. Now, all lessons can’t be Pixar movies. But the good stories (especially in literature and history) will challenge and subvert the binaries they begin with. Q: I see the pattern of Egan drawing from “as many cultures as possible”. Why so many? Is this a political correctness thing? If it helps to think of it as such, then, sure! I don’t think Egan would have had a problem with that. But his ultimate reason for including so much diversity goes deeper. For Egan, including such world-wide diversity isn’t optional, and the answer to why is bound up in his definition of education. (Keep reading.) His answer also insists that we, whenever possible, also include stories from the Bible and Homeric epics (the Iliad and Odyssey). Q: Mmm, stories from the Bible aren’t going to fly in my local school! So be it! Egan doesn’t spend much time obsessing over the practicalities of… His interest is in describing what an ideal education might look like, if it were possible. Every lesson, every classroom, and every school is necessarily a compromise. Q: You make a big deal of poems. But isn’t poetry dead? An interesting contrast can be made to classical education, which also has kids read a lot of poems — they see knowing great poems as one of the marks of an educated person; again, for an academicist, it’s the information that transforms. Egan begs to disagree. Poems are important because they’re a wonderful way to train their cognitive strengths, like rhythm (poems are language fueling by thumping). We want to help kids learn to use this tool better, and a great way to do that is to help them recite poems that they’ve learned by heart. Q: “Learn by heart” — is that code for “memorize”?! It is! Egan is actually quite big on memorization — he points out that all the knowledge in the world can do nothing for a person once they’ve forgotten it. He didn’t, however, appreciate the academicist focus on memorizing without understanding (or at least enjoyment). Q: I’m still worried about the science curriculum, as you’re describing it. Can you allay my fears? Honestly, while I feel there’s something profoundly right to how Egan is describing early experiences of nature, I feel the same way. Note that there’s more science coming in the social studies curriculum. But if that’s still not enough, one could bring down aspects of the middle school science stage. Q: Anything else that Egan suggests we do in elementary school literature and language? He suggests that we help kids learn a second language! This is so obviously true (why do American schools typically wait until kids lose the ability to naturally absorb languages to start teaching languages?) he doesn’t belabor it, though. Q: You had mentioned that Egan’s vision seems more internal-focused. Should we be worried about that? While I strongly suspect that his curriculum would make kids more creative in any way you’d like to measure it, Egan wasn’t particularly interested in “creativity” — he was more about helping kids find the world interesting. I get the sense that he thinks kids will do things with minimal prompting once they’re loaded up with complex internal experiences. Q: I think I’m beginning to understand Egan — is he basically saying “make learning fun”? “Fun”, applied to education, is a dangerous word. Egan worries about the dangers of an emotionally unserious curriculum producing emotionally stunted adults. That doesn’t mean we need to tell students only “serious” stories — only that we treat the world honestly. “Disney-esque sentimentality is the exact emotional equivalent to intellectual contempt”. Q: But aren't some of these stories too dark for children who have themselves experienced oppression and disaster? Egan argues that these stories may be especially helpful to them — they can help them understand their struggles better, and give voice to them. Q: At the very start of this, you promised us “rationality”… but I’m not seeing rationality here! All this talk of “adventure” almost seems to go the opposite direction. What gives? Wait for it. But for a hint right now — Egan is fond of citing his fellow educational theorist Jerome Bruner, who claimed “any subject can be taught effectively in some intellectually honest form to any child at any stage of development”. Bruner was criticized for that; his critics charged that he was ignoring learning differences and socio-economic realities. Egan thinks he was profoundly right. Part 3: A new kind of middle school What’s the matter with middle school? What was middle school like for you? In math, I recall a jumble of barely-related topics. In literature, I remember reading great literature — Frankenstein, Romeo and Juliet — only in their dumbed-down summary formats. In social studies, I remember teachers proclaiming on the first day of class that unlike all of our previous history classes, this class wouldn’t be about names and dates… and then going on to memorize names and dates. And in science, I remember being forced to dissect a frog only to discover that frogs are — you guessed it — made of slimy frog parts. Your mileage may vary, but for a lot of us, middle school feels like getting booted out of the (in retrospect) Eden of elementary school, and like marking time before the serious studying of high school. It feels meaningless. In my favorite of his books, Egan calls so much middle school curricula “human deserts”, noting “we have created a system in which the importance of human emotions for meaning seems barely noticed”. Why so meaningless? If our dominant approaches to educational psychology fundamentally misinterpret younger children, Egan suggests, they basically throw up their hands when faced with pre-teens and teenagers. Mainstream schools begin to introduce vocational training to help lighten the load, and Maria Montessori famously suggests that adolescents should be sent to go run a farm. Egan is sympathetic to those responses, but points out that they don’t do much to lighten the load that the academic curriculum often becomes at this age. This feeling of meaninglessness, he argues, is utterly tragic — it comes just when a hunger for meaning blossoms in adolescents! We can see that hunger for meaning in their lives outside the classroom, where their interests ramp up into veritable obsessions. What are adolescents obsessed with? What might we see, if we become Jane Goodalls of early adolescence? First, teens are obsessed with gossip. The motivations of others — why did he do that? and what was he THINKING? — are hypothesized and talked to death. Second, that they’re pulled toward idealism. Many feel a dissatisfaction with the world as it is, and feel a romantic urge to make it a better place. They’re often lured into simplistic beliefs that promise to help them do that. Third, they love extremes: they want to find limits, and test them. Obviously, this can show up as risky behavior, but we can also see it in their love for the bizarre — note adolescents’ fascination in things like aliens, cryptids, and ghosts. (Egan loves pointing out that The Guinness Book of World Records is a perennial bestseller among kids at this age. How else would they find out who had the world’s longest fingernails?) Fourth, they gravitate toward heroes — people who push the edges of those limits. By celebrating heroes, they can vicariously share in their transcendence. Look for the posts hanging up in a teenager’s bedroom to guess what boundaries they feel most hemmed in by: athletes push against physical limits; a death metal guitarist might push against authority and conventional morality. An activist or entrepreneur might push against our dulled morality or our sense of what’s possible. Finally, we might spot teens taking up hobbies and making collections. Hobbies can be a way to identify yourself as part of a group against the rest of the world (“I’m the sort of person who goes bird-watching!”), and collections can be a way to climb the status ladder inside the community. Egan points out that a collection can also be a way to feel like you have control over what you’re discovering is a very big and complex world of detailed information (“I’ve spotted every one of the fifty most common birds of Texas — even the black-capped vireo!”) Egan’s insight is that these obsessions give teenagers a sense of meaning, and that we can use them as tools to make middle schools that overflow with meaning. From meaningless to meaning-soaked Again, Egan sketches out a new kind of curriculum subject-by-subject. Before, his trick was to ask where the subject first evolved out of; now, it’s to ask who first discovered or created the specific content we’re teaching. “All knowledge”, he writes, “is human knowledge. Everything we know is knowable through the lives of its inventors, discoverers, or users, and we can have access to that knowledge through the hopes, fears, or intentions that drove them”. Middle school math Who first discovered the concepts students learn in math? The answer, of course, is a wide diversity of curious men and women living across the world over the last few thousand years. Egan says: bring those people into how we teach math. If we used gossip and heroes to help students find it meaningful, what kind of math would result? When we teach the Pythagorean theorem, we should give a sense of who Pythagoras was — a cult-founder who worshiped numbers to find God, whose followers (according to a piece of ancient gossip) murdered one of their members who discovered irrational numbers! Q: Well, sure, that works for Pythagoras, but he’s a known nut job; surely most math doesn’t come from such interesting roots? When we teach the Cartesian coordinate system, students should meet Rene Descartes, the Calvinist French polymath who saw the possibility that math could decipher the world, if only we could unite algebra and geometry… and invented the xy-plane to do exactly that. When we teach scientific notation, we should call our students’ attention to the importance of the number zero, and tell them the story of the Pope who tried to introduce Arabic numerals to Christian Europe and may have been assassinated because of it. When we teach algebra, we should ask students why “algebra” is Arabic for “the fixing of bones”, and tell the story of what Muhammad ibn Musa al-Khwarizmi was up to. We could do this all day. Literally everything students learn in school was first invented or discovered by some interesting person who was struggling to accomplish something hard. To learn is to connect with those people, whether we know it or not. Egan says: help kids know it. Math has been dehumanized: re-humanize it. Q: So the math curriculum needs to become a history of math curriculum, and math teachers need to become history teachers? No, the content needn’t change. But with surprisingly little work, we can bring in the gossipy stories of heroes, and their obsessions can spread to students. Middle school science Who first discovered the things students learn about in science? If you’re thinking “scientists”, you’re only partially right. Most of the big-picture ideas that we now think of as “science” were discovered before the word “scientist” was invented, or the discipline was professionalized. Frequently, they were hatched by true amateurs, working in their free time, hungry to unlock the secrets of nature. We can use gossip and heroes to spread their obsessions to students just as we taught math, but Egan points out two twists. The first is that the content itself can take on heroic qualities: everything is impressive, when you look at it in a certain light. In an interview, Egan once said: “My book is an attempt to show that, indeed, everything in the world is wonderful, but that schools are designed almost to disguise this slightly shameful fact. We represent the world to children as mostly known and rather dull. The opposite is the case: we are surrounded by mystery, and what we know is fascinating”. What would even the most boring subjects look like, if we emphasized their heroic qualities? Well: What’s a tooth? Bone, wrapped in rock, surrounding tiny cells that your body feeds with blood. What’s a bar of chocolate? A crystal of jellyfish-shaped fat molecules stacked together; when you put it in your mouth you shake them apart into a writhing confusion. What’s the air around you? The bottom of a 10-mile-deep ocean; when you put your tongue over a soda straw and your Pepsi stops leaking out, it’s not because a “vacuum” is “sucking” it up, but because that ocean is squeezing it into your face. Again, we could do this all day! And in middle school science, we can. Everything in the world is wonderful; we can help students see this again and again. The second twist is that science is a subject rich in extremes. Here Egan introduces a concept that we’ll see crop up again: “15-minute segments”. To help us fit as much wonder as possible into a school day, he suggests we supplement the usual school subjects with a few quick lessons. To infuse science with extremes, he suggests we add on three: “human & natural records”, “extremes of animals & plants”, and “cosmology”. Middle school history Who first made the things students learn about in history? Why, the historical characters themselves! Since we’ve given kids a grounding in history in elementary school, now we can build on that, going through many of the same events as before, but in more depth, and more vividly. We’ll leverage the interest with other people’s inner lives to tell stories focusing on the perspectives of the people who made history — zooming in, when possible, on scandalous details. We’ll leverage the tool of idealism to choose historical characters who chafed against their surroundings, and understand what they were trying to accomplish. What was their vision of the world? What did they hope for, and what did they fear? Q: Isn’t the “great man” approach to history out of fashion? Egan’s approach doesn’t say that “great men” made history — it’s just leveraging gossip to help kids see history as something meaningful that can expand their own possibilities. “Early adolescence is commonly a time of intense and vivid emotional life, and also a time of deepest boredom and depression… [We] can give shape to the intermediate curriculum and offer the students a world that is rich, complex, varied, and as intense and vivid as their own emotional lives”. We also should add on another “15-minute segment” just to pump in as many biographies as possible, and from people who don’t always fit into the normal history curriculum. Call it “Brief Lives”, and throw in anyone who’s struggled to push some limit — Mary Wollstonecraft, Jesse Owen, Dietrich Bonhoeffer, one of the students’ great-aunts, whoever. As students get older, this can transition to “People and Their Ideas”. Here, we’d focus less on the details of the person’s life, and use it as a backdrop to showing how meaningful some of history’s most important ideas could be. Think Aristotle and syllogisms, Edward Said and orientalism, Confucius and propriety, Cornel West and race, Buddha on the four noble truths, Muhammad and the five pillars, Karl Marx and communism, Adam Smith and the invisible hand, Thomas Hobbes and the state of nature, John Locke and natural rights, Jeremy Bentham and utilitarianism, Thomas Aquinas on the sacraments, Martin Luther on faith, Voltaire on the freedom of speech… you get the idea. Q: Can you really get a profound understanding of utilitarianism in 15 minutes? Yes! The point of this segment isn’t to develop a systematic understanding of any one idea, it’s to introduce students to the exciting possibilities of human thought. (As a bonus, this might make them less likely to fall for the first ideology that they encounter later in life.) Diversity is important for this — as it is with culture. Throughout this, we should also be trying to expose students to as much cultural diversity as possible, because in high school, we’ll be trying to make sense of our society, and it’s impossible to do that unless we have something to compare it against. Middle school literature & language You might think that this subject would be easy — that middle school literature is already filled with “strong and clear narratives”, that it deals with “transcendent human qualities such as courage, love, and persistence”, that it focuses on “extremes of human experience”, that it examines “something strange and exotic”. You’d be right! Egan’s pretty happy with a bog-standard middle school literature curriculum, done well. In this part of the book, his spends most of his limited space suggesting three rather odd activities which could also be useful — especially for increasing students’ awareness of language, so they can use it better. The first is etymology — not, however, memorizing lists of roots, but in being told the entertaining backstories of specific words. Take the word “berserk”, for example — we now use it to mean something relatively mild (“if my mom catches me coming home late, she’ll go berserk”), but it comes from an old Norse word meaning “a raging warrior of superhuman strength”. And that’s because ber meant “bear” and serk meant “shirt”: soldiers of the bear cult would don the skin of a bear to, in their minds, transform into one — howling, foaming at the mouth, and gnawing the rims of their shields. (Most adults walk through life with little understanding that the words falling out of their mouths are entities, with their own back-stories. Communication is, at the very least, more interesting when we become aware of this.) The second is to add on another language to learn — not, this time, to become fluent in it, but just to become aware of how very different human languages can be. (For native English speakers, Sanskrit might work well, or Cantonese, or perhaps even ancient Egyptian. Again, the point isn’t for this language to be useful — it’s to explore diversity.) The final one is to study humor — not just jokes anymore, but comedy at its finest. Egan cites (at length!) Monty Python as a group of people who were particularly brilliant in their use of the English language. Examining their skits can lead us into not just an appreciation of semantics (the study of how meaning is made from smaller pieces, like etymology) but also pragmatics (the study of how meaning is made in social situations). Pretty heady stuff, for a conversation about a dead parrot. Part 4: A new kind of high school I’ll confess — I loved parts of high school… and among nerdy folks, I suspect I’m not alone. For some of us, this was a golden time. Even at my local public high school, I had access to academically thrilling classes — especially, in my last two years, advanced literature and history. I felt like I was finally understanding the ideas that mattered. In any case, Egan is quick to acknowledge that, at this level, the sort of education he advocates really is being practiced in some places. What he can add is an understanding of what makes it wonderful, how to make it even more wonderful, and how to make it wonderful for many, many more people. What’s the matter with high school? Far too often, even when high school classes are intellectual, they’re dry. For the majority of students, all this academic stuff is experienced as utterly lifeless, a mass of dead information to be squeezed inside one’s head for a test and then left to evaporate. Egan mocks the curriculum wars that seem to be a permanent feature of the teaching life; quoting the sociologist Pierre Bourdieu, he says “while the academic left and right bicker over whether the curriculum is too traditional or too radical, they fail to recognize that most students absorb so little of academic culture that the bickering is largely irrelevant”. Why so dry? Egan suggests three reasons to explain this. First, because high school academic classes are too often masses of small details with no sign of the big picture. Second, because they’re typically slavishly disciplinary, and aren’t able to address the questions that span the disciplines. Third, because they’re often designed to bring students through what everyone is sure of, and hide away any controversies. In all of these, Egan suggests that what’s called “academics” in high school is too often a dim imitation of what real academics are actually practicing. There’s a fourth reason, though, and it’s probably the biggest of all — by the time they get to high school, most students haven’t actually learned that much! An academic approach is designed to connect small details into the big picture; for people who arrive in high school (and college) classes without having already collected much in their heads, academics are going to taste dry. (An implication of this for anyone trying to improve schools is that we might not want to start with high schools. If your goal is to create a new kind of academic learning, first start at elementary school — or barring that, middle school.) What motivates mad scientists? When we wanted to re-conceive the elementary and middle school curriculums, we looked at what students were already good at — kids’ cognitive strengths and adolescents’ obsessions. For this level it might be easier to look — for reasons that will become clear when we finally unveil Egan’s crazy-sounding definition of education — at the sorts of things that bring intellectuals joy. Q: Which intellectuals? Take your pick. Galileo, Einstein, Smith, Marx, Goodall, Chomsky, Curie… all the people who took to the life of the mind like fish to water. But that’s a lot to hold in my mind at once, so I’m just going to think about Doc Brown from Back to the Future: He was high on intellectualism I’ve never been there, but the brochure looks nice Let’s call these people “mad scientists”. And let’s pretend we once again took up our job of being primatologists, and snooped on these folks “in the wild” (“in the lab”? this is beginning to get recursive…)… what would we find motivating them? Asking simple questions, for one. (What is space? What is society? What is a human? What is language?) Building general schemes (big theories) that hold lots of evidence together. Finding their place in the cosmos. And (perhaps above all) seeking certainty. Once again, Egan suggests we use these as tools to remake the curriculum. From dry to daring What could a high school curriculum look like, if it were rebuilt on these tools? Once again, Egan has a trick. This time, it’s to ask what fights have driven the development of each of these fields forward — and how we can help students enter them. First, a mini-segment! Intellectuals invented the academic disciplines to better pursue the life of the mind, but the disciplines can get in the way. Some of the most important intellectual discoveries that could help students are too big to fit into any of the disciplines. We need a place to introduce them plainly. Egan proposes another mini-segment — again, just 15 minutes a day, a few times a week — called “Metaknowledge”. Q: Isn’t that already in the International Baccalaureate program? Yes, he acknowledges that he’s borrowing from that! This segment would introduce ideas that would enrich student thinking across the disciplines: game theory, cognitive biases, systems thinking, Bayesian reasoning, epistemology, ethics, logic, cultural evolution, and so on. High school literature How can we help students enter the big fights of literature? Intellectuals of a literary bent — professors, critics, poets, novelists — delight in arguing over literature like rabbis arguing over the Talmud. Take, just for one example, the debates over Shakespeare’s character of Ophelia. Does she love Hamlet, or is she a victim of his emotional abuse? Is she truly insane, or is she acting? Is she passive, or is she pulling the strings? Oceans of ink have been spilled arguing over questions like these; our students can, perhaps, spill a few ounces more. The usefulness of arguing literature, for Egan, isn’t that it’s oh-so important for educated adults to know a lot about Ophelia. (This, again, was where the academicists went wrong — in thinking that being educated was about getting the best knowledge in your head.) Rather, arguing over literature is a training arena for the all-important intellectual move of this kind of understanding: building general schemes out of evidence, and struggling with anomalies. One person, for example, might hold that Ophelia is insane, and cite all sorts of obvious evidence — her father just was murdered by her lover, she rants nonsense while (bizarrely) handing out flowers to friends… But then he’s challenged when he reads a scholar pointing out that, to people in Elizabethan England, types of flowers have symbolic meanings. How does he deal with that? He could ignore it, claiming it an over-reading of Shakespeare. (Sometimes a flower is just a flower!) Or he could address it, complicating his own scheme. This intellectual work is best done with other people, who are incentivized to challenge your understanding of something, and go back and forth, building competing models and calling attention to anomalies. This process — the “dialectic” — pops up again and again in the academic disciplines. It’s the center of how understanding works, at this stage. And the nice thing about practicing it on literature is that, more so than in history or science, the evidence is shared knowledge — it’s right in front of everyone, written out. But there are other ways literature class can be helpful to the general life of the mind. Egan also suggests that we’ll want to specially include literature that helps students understand complex ideas. Camus, Orwell, Borges, Calvino might be particularly helpful here… and I imagine that genres like science fiction and magical realism might be particularly useful, too. (Note, though, that once again none of this requires a radical remaking of the curriculum, or of the canon of texts that we traditionally assign to high schoolers.) Q: Oh yes, the canon — what does Egan have to say about the canon wars? When he wrote Educated Mind in the nineties, the long-brewing canon war was approaching its inevitable apocalyptic climax. On one side of this Plain of Megiddo were the pro-canon traditionalists, arguing that we should keep assigning the texts that had been argued over for centuries. Facing them were the anti-canon reformers, arguing the standard texts over-represented the perspective of dead white men. Onto the middle of the plain rides Egan on a white horse, who bellows above the din: “I’VE GOT A BUSLOAD OF HIGH SCHOOLERS WHO WANTS TO JOIN IN, EVERYONE OKAY WITH THAT?” To do so, he says, we need to give students the arguments from both sides. So, for example, bell hooks, Edward Said, and China Achebe should be on the syllabus, as should Allan Bloom, Mortimer Adler, and Diane Ravitch. And of course they should actually read the texts cherished by both sides, too, so they can argue better. High school history How could entering the big fights help us reinvent high school history? First, we might look for dueling histories. It’s time for students to get into historiography and understand that history isn’t just what happened, it’s something we make. We might help kids read chapters from Howard Zinn’s socialist history of America alongside the corresponding chapters from Paul Johnson’s conservative history of America. How could big questions help? We want to help students see how various people have disagreed over some of the big questions of what human history is, at its most basic. We can have them compare Steven Pinker’s theory of civilization’s progress (Better Angels of our Nature) with Yuvah Noah Harari’s theory of civilization’s woes (Sapiens). We could have them compare so-and-so’s account of human history as an ever-expanding unlatching of energy sources with Robert Wright’s account of human history as unlatching more and more positive-sum games (Nonzero). What role could the lure of certainty play? To help them grow their skills at finding anomalies, we might help them work through pseudo-histories and conspiracy theories. Q: Conspiracy theories! Oh, come now, you’re playing with fire. Well, the world is on fire. Our students will spend the rest of their lives encountering terrible-but-beguiling arguments about how the world works; if we don’t prepare them for those, what have we been doing? So we should introduce arguments that the Moon landing was a hoax, that the Illuminati founded America, that aliens built the pyramids, and so on. At no point can we demean students for falling for any of these theories — the job of a teacher at this stage, Egan writes, is to support students in their reasoning even when their beliefs are offensive and stupid, gradually offering anomalies. There’s no way out of bad theories except through them. By the time students graduate, we want them to have wrestled with terrible ideas and — for a while — lost. They need to experience what it’s like to change their minds about something they felt strongly about. They need to viscerally realize, in Feynman’s famous phrase, “The first principle is that you must not fool yourself and you are the easiest person to fool.” High school natural science How could entering the big fights reinvent high school science? At present, so much of the high school science curriculum — especially “honors” classes — is oriented toward helping amass details. (The same is true of 100-level university classes, which famously “survey” the field to prepare for more advanced studies. I always thought this was stupid — of the huge lecture hall of students in my Geology 100 class, how many went on to take even a second course?) The meaty debates that propel science forward are held back. Egan complains: “The more general and speculative theories in any discipline are treated like an unconventional and disreputable relation who, even though the children find her exciting and entertaining, must be kept hidden from view, her very existence denied as long as possible”. This is a stupid approach — students with an adventurous bent are convinced that science isn’t for them. Egan proposes, simply, that we flip this, and organize high school science classes around the big debates. We shouldn’t be ashamed at how, well, adolescent this might look: “the dramatic, speculative, and contentious theories will be up-front in the early years of the [high school] curriculum”. What might those be? Egan doesn’t give a list, but we can spitball some: instead of explaining what “matter” is from the top down, a physics class could problematize “matter” by following the debates over the nature of dark matter and dark energy, and by becoming familiarized with the various interpretations of quantum mechanics
January 29, 2025 · Original source
“Too many to type out here, but radically transformed my life - directly led to quitting career and feeling cool without ever knowing what happens next, put right and left hemispheres in proper order (only really understood 6 years later when reading McGilchrist) and totally blew open my heart, leading to finding Disney-magic love a few months later, a state I've been living and smiling in ever since :)”
Duolingo

Duolingo is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 14, 2021 and June 27, 2025. The archive places it in contexts such as "more languages with Duolingo"; "Foreign Language (mostly on duolingo)". It most often appears alongside India, Khan Academy, YouTube.

Article page
Duolingo
Mention count
2
Issue count
2
First seen
May 14, 2021
Last seen
June 27, 2025
May 14, 2021 · Original source
You might remember the gamification craze from the beginning of this decade. App creators were convinced that adding badges, randomness, and leveling up to any activity would make it irresistible. We were promised a new world where the power of gaming would be used for good. We would all chase after more steps with our Fitbits, more languages with Duolingo, and more math with Khan Academy. Move aside Portal and poker, there were new sheriffs in town.
And yet, despite following a lot of the same strategies that gambling machine designers did, those app creators never did create an army of self-improvement addicts. I haven’t heard any tales of someone losing his job because he was too busy getting more steps with his Fitbit, neglecting her marriage because she was too busy learning a new language on Duolingo, or dropping out of school to make more time for Khan Academy. Why is that? If designers can turn creaky slot machines into a multibillion dollar addictive product, why couldn’t they do the same for all these virtuous apps? Why can I, a person who gets addicted to apps fairly easily, not bring myself to spend more than ten minutes on Duolingo? Why are these apps still more broccoli than chocolate?
June 27, 2025 · Original source
Foreign Language (mostly on duolingo)
escitalopram

escitalopram is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 31, 2021 and May 25, 2021. The archive places it in contexts such as "Lexapro (escitalopram) is a derivative of the older drug Celexa"; "the purely sinister escitalopram is more than twice as effective as the racemic mixture"; "Most patients will want either escitalopram or bupropion as first-line treatment". It most often appears alongside FDA, imipramine, SSRIs.

Article page
escitalopram
Mention count
2
Issue count
2
First seen
March 31, 2021
Last seen
May 25, 2021
March 31, 2021 · Original source
What is the right dose of Lexapro (escitalopram)?
Because Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram). Sometime around 2011, the FDA freaked out that high doses of citalopram might cause a deadly heart condition called torsade de pointes, and lowered the maximum dose to prevent this. Since then it's been pretty conclusively shown that the FDA was mostly wrong about this and kind of bungled the whole process. But they forgot to ever unbungle it, so citalopram still has a lower maximum dose than every other antidepressant. When escitalopram was invented, it inherited its parent chemical's unusually-low maximum dose, and remains at that level today [edit: I got the timing messed up, see here]
Now that we know the heart risk was overblown, should we increase the maximum dose to something closer to other SSRIs? Maybe not. Right now, escitalopram keeps showing up in studies and head-to-head comparisons as the most effective SSRI.
May 25, 2021 · Original source
The short version: Depression has a combination of biological, psychological, and social causes. You can address the social causes by changing your life circumstances (and research suggests people underestimate the potential benefits of making major life changes). You can address the psychological causes with therapy; possible therapies are diverse and complicated but I especially recommend “behavioral activation” therapy (where you try to keep a schedule and also do new, interesting things) and David Burns’ book Feeling Good. You can address the biological causes with a combination of lifestyle changes, medications, and supplements. Consider exercising more and adapting a modified Mediterranean diet. Consider taking antidepressants like escitalopram and bupropion, and supplements like l-methylfolate. Other non-chemical biological options include light therapy (safe and easy), transcranial magnetic stimulation (more complicated), and electroconvulsive therapy (difficult but extremely effective last-ditch solution). If something treats your depression, continue it for some length of time depending on the type of intervention, then consider withdrawing it to see if you can maintain your mood without it.
Most patients will want either escitalopram or bupropion as first-line treatment. These medications are easy to use and have fewer side effects than most others.
Advantages of escitalopram: it’s slightly better at dealing with anxiety, rumination, and obsessive thoughts, although some studies have challenged this. Disadvantages of escitalopram: it frequently decreases sex drive/ability/performance, and occasionally causes tiredness, weight gain, or emotional flatness. Read more at my page on SSRIs.
Facebook Threads

Facebook Threads is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 13, 2023 and September 18, 2023. The archive places it in contexts such as "Easily survived a challenge from Facebook Threads"; "then found they didn’t like Mastodon and went back? Was it Mastodon after all? Facebook Threa". It most often appears alongside Ashlee Vance, Boeing, Elon.

Article page
Facebook Threads
Mention count
2
Issue count
2
First seen
September 13, 2023
Last seen
September 18, 2023
September 13, 2023 · Original source
Easily survived a challenge from Facebook Threads.
September 18, 2023 · Original source
For example, I’m surprised to hear this! I thought there was a week or two when everyone threatened to switch to Mastodon, then found they didn’t like Mastodon and went back? So where did everyone go? Was it Mastodon after all? Facebook Threads? Blue Sky? Or did they all start learning to paint and spending time with their friends and families?
Falcon 9

Falcon 9 is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 13, 2023 and August 14, 2025. The archive places it in contexts such as "Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9"; "worked on the guidance and navigation software for the Falcon 9 first stage landing". It most often appears alongside SpaceX, A. Bejanin, A. de Calignon.

Article page
Falcon 9
Mention count
2
Issue count
2
First seen
September 13, 2023
Last seen
August 14, 2025
September 13, 2023 · Original source
When SpaceX was on its last few hundred thousand dollars, and the Falcon 1 kept blowing up, and no private company had ever launched a rocket to space before, and they only had a few weeks to make Falcon 1 fly and restore investor confidence before the company went bankrupt - Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9. The same thing happened with the Tesla Roadster and the Model S.
August 14, 2025 · Original source
Some years ago, I worked on the guidance and navigation software for the Falcon 9 first stage landing. The early attempts failed because of annoying issues like stuck propellant valves, running out of fin hydraulic fluid, and so on. It took many tries to iron out all those issues. Meanwhile, fans and critics kept proposing that SpaceX’s fundamental approach was flawed, and suggesting entirely different approaches. Most of that criticism was pretty uninformed.
GM

GM is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 25, 2021 and June 23, 2023. The archive places it in contexts such as "Distribution 1 represents car companies in your region. Again, it has low variance, so they're all pretty similar. Ford vs. GM"; "what’s good for GM is good for America"; "GM still denies this last part". It most often appears alongside 1965, 1968 Summer Olympics, 2000 election.

Article page
GM
Mention count
2
Issue count
2
First seen
March 25, 2021
Last seen
June 23, 2023
March 25, 2021 · Original source
Okay, now suppose that Distribution 1 represents car companies in your region. Again, it has low variance, so they're all pretty similar. Ford vs. GM, something like that.
June 23, 2023 · Original source
By his early twenties, Nader had become something of a hotshot at Harvard Law School, where he developed an interest in vehicle safety after one of his classmates was injured in a car crash. Post-World War II, highway construction had boomed and vehicle sales had boomed along with it, with U.S. car ownership tripling in the two decades following 1946. It was the era of Robert McNamara’s famous quote that “what’s good for GM is good for America.” But these cars were also pretty dangerous, with a per-capita vehicle death rate more than twice today’s. At Harvard, Nader proposed the then-groundbreaking, but now widely accepted, “double-injury theory”: the idea that a car accident is best conceptualized as consisting of two separate injuries, first the car itself hitting something and then the passengers hitting the inside of the car6.
GM still denies this last part, but it definitely happened.
GMail

GMail is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 02, 2023 and June 28, 2023. The archive places it in contexts such as "so-and-so has a GMail account or Facebook page and has gotten lots of normal-looking messages over many years"; "I can no longer write things on Gmail"; "I have to compose on Notepad and then copy-paste to the Gmail window". It most often appears alongside Google, Substack, Act Blue.

Article page
GMail
Mention count
2
Issue count
2
First seen
February 02, 2023
Last seen
June 28, 2023
February 02, 2023 · Original source
Sites could ask for proof of humanity. I don’t know how this will work in the future: drivers licenses can be faked, videos can be spoofed. Worst case scenario, I think megacorporations like Google and Facebook could offer this as a service - so-and-so has a GMail account or Facebook page and has gotten lots of normal-looking messages over many years.
June 28, 2023 · Original source
An unblockable moving status bar that switches every few seconds between different messages about the product! This is what they think the people most obsessed with blocking flashing/changing elements on websites want! This new “show a constantly-moving status bar on screen to tell you when they will change another flashing element” thing has also made it onto the front page of Bing, although luckily you can dismiss it there. I would have expected Google to resist. They haven’t. I can no longer write things on Gmail - I have to compose on Notepad and then copy-paste to the Gmail window - because they’ve made it look like this: It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
How do I delete the words “Draft Saved” from the Gmail box?
Google Docs

Google Docs is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 25, 2021 and September 30, 2024. The archive places it in contexts such as "we exceeded Google Docs’ puny character limit"; "You can use Google Docs or OpenBallot". It most often appears alongside ACX, Austin, Berkeley.

Article page
Google Docs
Mention count
2
Issue count
2
First seen
April 25, 2021
Last seen
September 30, 2024
April 25, 2021 · Original source
3: Reminder for those of you who didn't see this last week: I have a list of all 80-something non-finalists in the Book Review Contest. You can see it here: Volume One (A-R), Volume Two (S-W) (we exceeded Google Docs’ puny character limit, so it’s split in half). Your mission, should you choose to accept it, is to read some number of them (even one is okay!) and then vote using this form. Please choose a random one to read each time, or select the one that looks most interesting to you, but don’t start from the beginning - if we have 5000 votes for the ones beginning with “A” and none for the ones beginning with “W”, that breaks the whole point. Choose a random one and vote on it with the form. If you read 50, you can either save them all up for one form, or send 50 forms, either way is okay (note that the form asks for your email so I can investigate potential voting irregularities; I won’t share this with anyone else). At the end, I’ll average all the ratings I have for each book, and declare the top-rated runners-up to be new finalists (in addition to the finalists I’ve already chosen). If you have questions about any of this, or you can’t access any of the relevant pages, please comment below. If you can’t get the Google Docs file to load, here’s PDFs of Volume 1 and Volume 2.
September 30, 2024 · Original source
You hold your ballot meetups and get me your recommendations by October 21. You can use Google Docs or OpenBallot.
Google Forms

Google Forms is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 16, 2022 and August 01, 2024. The archive places it in contexts such as "If you can put a name/time/date in a box on Google Forms and show up there"; "If you can put a name/time/date in a box on Google Forms". It most often appears alongside ACX, Scott, Astralcodexten.

Article page
Google Forms
Mention count
2
Issue count
2
First seen
August 16, 2022
Last seen
August 01, 2024
August 16, 2022 · Original source
If you can put a name/time/date in a box on Google Forms and show up there, you have the minimum skill necessary to be a meetup organizer for your city, and I would recommend you sign up.
I also recommend collecting people’s names/emails — the best way to do this is to have people scan a QR code or follow a bitly link, to either fill out a Google Form or add themselves to an existing mailing list / group chat / etc. I used to recommend just pen and paper for this, but it turns out reading people’s handwriting is hard.
August 01, 2024 · Original source
People enjoy each other’s company and keep having meetups throughout the year. The form will ask you to pick a location, time, and date, and to provide an email address where people can reach you for questions. It will also ask a few short questions about how excited you are to run the meetup to help pick between multiple organizers in the same city. One meetup per city will be advertised on the blog, and people can email you if they have questions. Organizing an ACX Everywhere meetup can be easy. Pick a time and a place (parks work well if you think there will be a lot of people, cafes or apartments work fine for fewer) and show up with a sign saying “ACX Meetup.” You don’t need to have discussion plans or a group activity. If you want to make the experience better for people, you can bring nice things like nametags/markers, food/drinks, or games. Meetups Czar Skyler can reimburse you for the nametags, markers, food, and drinks. If you feel more ambitious, collect people’s names and emails if they’re interested in future meetups. You could do this with a pen and paper, or if you’re concerned about reading people’s handwriting, you could use a QR code/bitly link to a Google Form. Here’s a short FAQ for potential meetup organizers: 1. How do I know if I would be a good meetup organizer? If you can put a name/time/date in a box on Google Forms and show up there, you have the minimum skill necessary to be a meetup organizer for your city, and I recommend you sign up. Don't worry, you signing up won't randomly take the job away from someone else. The form will ask people how excited/qualified they are about being an organizer, and if there are many options, I'll choose whoever I think is best. (Or plausibly whoever Meetup Czar Skyler thinks is best.) But a lot of cities might not have an excited/qualified person, in which case I would rather the unexcited/unqualified people sign up, than have nobody available at all. This spreadsheet shows the cities where someone has filled out the form, updated manually after a basic check. Lots of cities have existing meetup groups and we’ll probably prioritize them, but we always appreciate more options. Last time there were some people who didn’t volunteer because they just assumed their city was big enough that someone else would do it. Beware the Bystander Effect! If you are the leader of your city’s existing meetup group, please fill in the form anyway and say so. 2. How will people hear about the meetup? You give me the information, and on August 23 (or so), I’ll post it on ACX. An event will also be created on LessWrong’s Community page. 3. When should I plan the meetup for? Since I’ll post the list of meetup times and dates around August 23, please choose sometime after that. Any day September 1st through October 31st is okay. I recommend a weekend, since it's when most people are available. You’ll probably get more attendance if you schedule for at least one week out, but not so far out that people will forget - so mid September or early October would be best. Check your local calendar for holidays where people might be busy: If you're in the US, that probably means avoid Labor Day and Halloween. 4. How many people should I expect? The last time we tried this, meetups ranged from one person to over a hundred. Meetups in big US cities (especially ones with universities or tech hubs) had the most people; meetups in non-English-speaking countries had the fewest. You can see a list of every city and how many people most of them got last time here. Plan accordingly. 5. Where should I hold the meetup? A good venue should be easy for people to get to, not too loud, and have basic things like places to sit, access to toilets, and the option of acquiring food and water. City parks and mall common areas work well. If you want to hold the meetup at your house, remember that this will involve me posting your address on the Internet. 6. What should I do at the meetup? Mostly people just show up and talk. If you’re worried about this not going well, here are some things that can help: Have people indicate topics they’re interested in by writing something on their nametag
Google Imagen

Google Imagen is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 12, 2022 and July 08, 2025. The archive places it in contexts such as "Google Imagen announced May 2022"; "In September 2022, I got some good results from Google Imagen"; "when Google Imagen produced the following". It most often appears alongside DALL-E2, Gary Marcus, GPT.

Article page
Google Imagen
Mention count
2
Issue count
2
First seen
September 12, 2022
Last seen
July 08, 2025
September 12, 2022 · Original source
Google Imagen announced May 2022.
Imagen: 3/5
Imagen got 3/5 and so I would say it wins the bet. There was one snafu, which was that for trust-and-safety reasons, Imagen will not represent the human form (maybe it’s a good Muslim?) We got around this by replacing all humans in the prompts with robots. It still registered surprisingly many trust-and-safety violations for these innocuous prompts, but here’s what we got (slightly edited to always include the best picture of 10):
July 08, 2025 · Original source
In September 2022, I got some good results from Google Imagen and announced I had won the three-year bet in three months. Commenters yelled at me, saying that Imagen still hadn’t gotten them quite right and my victory declaration was premature. The argument blew up enough that Edwin Chen of Surge, an “RLHF and human LLM evaluation platform”, stepped in and asked his professional AI data labelling team. Their verdict was clear: the AI was bad and I was wrong. Rather than embarrass myself further, I agreed to wait out the full length of the bet and re-evaluate in June 2025.
Three months later, I declared premature victory when Google Imagen produced the following:
User askwho on the Bayesian Conspiracy Discord claimed that Google Imagen passed the test in September 2024 (he said Imagen 2, but based on the timing it may have been Imagen 3). But he didn’t post it publicly and couldn’t remember all details, so I’ll evaluate this related claim, also about Imagen 3, from December:
GrubHub

GrubHub is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 30, 2021 and April 22, 2025. The archive places it in contexts such as "every time I order food from GrubHub"; "I’m giving GrubHub drivers $3"; "Now that I think about it, I haven’t heard much from GrubHub or UberEats lately". It most often appears alongside UberEats, 80,000 Hours, @msamalam.

Article page
GrubHub
Mention count
2
Issue count
2
First seen
August 30, 2021
Last seen
April 22, 2025
August 30, 2021 · Original source
One more example: every time I order food from GrubHub, I get a menu like this:
I find I usually click the third box on both. I want to tip generously, but giving the maximum possible tip seems profligate. Surely the third box is the right compromise. I recently noticed that this is insane. For a $35 meal, I’m giving GrubHub drivers $3 and UberEats drivers $7 for the same service (or maybe there’s some difference between their services which makes UberEats suggest the higher tip - but if there is, I don’t know about it and it doesn’t affect my decision). Again, this is Behavioral Economics 101 - in particular, one of the many biases lumped together under menu effects. Instead of being a rational economic actor who values food delivery at a certain price, I’m trying to be a third-box-of-four kind of guy. That means that whoever is in charge of this menu has lots of power over the specific dollar amount I give. Not infinite power - if the third box said $1000 I would notice and refuse. But enough power that “nudging” seems like a fair description. Nobody believes studies anymore, which is fair. I trust in a salvageable core of behavioral economics and “nudgenomics” because I can feel in my bones that they’re true for me and the people around me. Let’s move on to Hreha’s article and see if we can square it with my belief in a “salvageable core”. II. Yechaim’s Historical Detective Story Hreha writes: The biggest replication failures relate to the field's most important idea: loss aversion. To be honest, this was a finding that I lost faith in well before the most recent revelations (from 2018-2020). Why? Because I've run studies looking at its impact in the real world—especially in marketing campaigns. If you read anything about this body of research, you'll get the idea that losses are such powerful motivators that they'll turn otherwise uninterested customers into enthusiastic purchasers. The truth of the matter is that losses and benefits are equally effective in driving conversion. In fact, in many circumstances, losses are actually *worse* at driving results. Why? Because loss-focused messaging often comes across as gimmicky and spammy. It makes you, the advertiser, look desperate. It makes you seem untrustworthy, and trust is the foundation of sales, conversion, and retention. "So is loss aversion completely bogus?" Not quite. It turns out that loss aversion does exist, but only for large losses. This makes sense. We *should* be particularly wary of decisions that can wipe us out. That's not a so-called "cognitive bias". It's not irrational. In fact, it's completely sensical. If a decision can destroy you and/or your family, it's sane to be cautious. "So when did we discover that loss aversion exists only for large losses?" Well, actually, it looks like Kahneman and Tversky, winners of the Nobel Prize in Economics, knew about this unfortunate fact when they were developing Prospect Theory—their grand theory with loss aversion at its center. Unfortunately, the findings rebutting their view of loss aversion were carefully omitted from their papers, and other findings that went against their model were misrepresented so that they would instead support their pet theory. In short: any data that didn't fit Prospect Theory was dismissed or distorted. I don't know what you'd call this behavior... but it's not science. This shady behavior by the two titans of the field was brought to light in a paper published in 2018: "Acceptable Losses: The Debatable Origins of Loss Aversion". I encourage you to read the paper. It's shocking. This line from the abstract sums things up pretty well: "...the early studies of utility functions have shown that while very large losses are overweighted, smaller losses are often not. In addition, the findings of some of these studies have been systematically misrepresented to reflect loss aversion, though they did not find it." When the two biggest scientists in your field are accused of "systemic misrepresentation", you know you've got a serious problem. Which leads us to another paper, published in 2018, entitled "The Loss of Loss Aversion: Will It Loom Larger Than Its Gain?". The paper's authors did a comprehensive review of the loss aversion literature and came to the following conclusion: "current evidence does not support that losses, on balance, tend to be any more impactful than gains." Yikes. But given the questionable origins of the field, it's not surprising that its foundational finding is *also* dubious. If loss aversion can't be trusted, then no other idea in the field can be trusted. This argument relies on two papers - Yechaim’s Acceptable Losses and Gal & Rucker’s Loss Of Loss Aversion. Yechaim’s paper is a historical detective story. It looks at how Kahneman and Tversky first “discovered” and popularized the idea of loss aversion from earlier 1950s and 1960s research. It concludes they did a bad job summarizing this earlier research; looked at carefully, it doesn’t support the strong conclusions they drew. From one perspective, nobody should care about this. All the 1950s and 1960s research was terrible - one of the most important studies it discusses had n = 7. Since then, we’ve had much more rigorous studies of tens of thousands of people. All that hinges on Yechaim’s paper is whether Kahneman and Tversky were personally bad people. Hreha thinks they were. He calls their behavior “shady”, “shocking”, and says they “systematically misrepresented findings to support their pet theory…I don't know what you'd call this behavior... but it's not science.” Again, nothing important really hinges on this, but I feel like fighting about it, so let’s look deeper anyway. Here’s how Yechaim summarizes his accusation against K&T: In addition, the results of several studies seem to have been misrepresented by Fishburn and Kochenberger (1979) and Kahneman and Tversky (1979). Galenter and Pliner (1974) were wrongly cited as showing loss aversion, whereas, in fact, they did not observe an asymmetry in the pleasantness ratings of gains and losses. Likewise, in Green (1963), the results were argued to show loss aversion, even though this study did not involve any losses. In addition, the objective outcomes for some of the participants in Grayson (1960) were transformed by Fishburn and Kochenberger (1979) so as to better support a model assuming different curvatures for gains and losses (see Table 1). Finally, studies showing no loss aversion or suggesting aversion to large losses were not cited in Fishburn and Kochenberger (1979) or in Kahneman and Tversky (1979). Yechaim bases his argument on three sets of early studies of loss aversion: Galenter and Plinter (1974), Fishburn and Kochenberger’s review (1979) and miscellaneous others. —Galenter and Plinter— is actually really neat! It explores “cross-modal” perceptions of gains versus losses. That is, if you ask how much a certain loss hurt, people will probably just say something like “I dunno, a little?” and then it will be hard to turn that into a p-value. G&P solve this by making people listen to loud noises, and asking questions like “is the difference between how much loss A and loss B hurt greater or lesser than the difference between the volume of noise 1 and noise 2?” The idea is that the brain uses a bunch of weird non-numerical scales for everything, and we understand its weird-non-numerical scale for noise volume pretty well, and so maybe we can compare it to how people think about gains or losses. I don’t know why people in 1974 were doing anything this complicated instead of inventing the basic theory of loss aversion the way Kahneman and Tversky would five years later, but here we are. Anyway, Yechaim concludes that this study failed to find loss aversion: Summing up their findings, Galenter and Pliner (1974) reported as follows: “We now turn to the question of the possible asymmetry of the positive and negative limbs of the utility function. On the basis of intuition and anecdote, one would expect the negative limb of the utility function to decrease more sharply than the positive limb increases... what we have observed if anything is an asymmetry of much less magnitude than would have been expected ... the curvature of the function does not change in going from positive to negative” (p. 75). Thus, our search for the historical foundations of loss aversion turns into a dead end on this particular branch: Galenter and Pliner (1974) did not observe such an asymmetry; and their study was quoted erroneously [by Kahneman and Tversky]. I looked for the full text of Galenter and Pliner, but could not find it. I was however able to find the first two pages, including the abstract. The way Galenter and Pliner summarize their own research is: Cross-modality matching of hypothetical increments of money against loudness recover the previously proposed exponent of the utility function for money within a few percent. Similar cross-modality matching experiments for decrements give a disutility exponent of 0.59, larger than the utility exponent for increments. This disutility exponent was checked by an additional cross-modality matching experiment against the disutility of drinking various concentrations of a bitter solution. The parameter estimated in this fashion was 0.63. If I understand the bolded part right, the abstract seems to be saying that they did find loss aversion! I was also able to find the Google Books listing for the book that the study was published in. Its summary is: Three experiments were conducted in which monetary increments and decrements were matched to either the loudness of a tone or the bitterness of various concentrations of sucrose octa-acetate. An additional experiment involving ratio estimates of monetary loss is also reported. Results confirm that the utility function for both monetary increments and decrements is a power function with exponents less than one. The data further suggest that the exponent of the disutility function is larger than that of the utility function, i.e., the rate of change of 'unhappiness' caused by monetary losses is greater than the comparable rate of 'happiness' produced by monetary gains. (Author). Again, the way the book is summarized (apparently by the author) says this study does prove loss aversion. Without being able to access the full study, I’m not sure what’s going on. Possibly the study found loss aversion, but it was less than expected? Still, I feel like Yechaim should have mentioned this. At the very least, it decreases Kahneman and Tversky’s crime from “lied about a study to support their pet theory” to “credulously believed the authors’ own summary of their results and didn’t dig deeper”. But also, why did the authors believe their study showed loss aversion? Why does Yechaim disagree? Without being able to access the full paper, I’m not sure. —Green 1963— is the second study that Yechaim accuses K&T of misrepresenting. Here’s how K&T cite this study in their paper: It is of interest that the main properties ascribed to the value function have been observed in a detailed analysis of von Neumann-Morgenstern utility functions for changes of wealth (Fishburn and Kochenberger [14]). The functions had been obtained from thirty decision makers in various fields of business, in five independent studies [5, 18, 19, 21, 40]. Most utility functions for gains were concave, most functions for losses were convex, and only three individuals exhibited risk aversion for both gains and losses. With a single exception, utility functions were considerably steeper for losses than for gains. Green 1963 is footnote 19. So K&T don’t even mention it by name. They mention it as one of several studies that a review article called Fishburn and Kochenberger analyzes. F&K are reviewing a bunch of studies of executives. In each study, a very small number of executives (usually about 5-10 per study) make a hypothetical business decision comparing gains and losses, for example: Suppose your company is being sued for patent infringement. Your lawyer’s best judgement is that your chances of winning the suit are 50–50; if you win, you will lose nothing, but if you lose, it will cost the company $1,000,000. Your opponent has offered to settle out of court for $200,000. Would you fight or settle? Then they ask the same question with a bunch of other numbers, and plot implied utility functions for each executive based on the answer. Green is one of these five studies, and it does superficially find loss aversion. But Fishburn and Kochenberger have done something weird. They argue that “loss” and “gain” aren’t necessarily objective, and usually correspond to “loss relative to some reference frame” (so far, so good). In order to figure out where the reference frame is, they assume that the neutral point is wherever “something unusual happens to the individual’s utility function” (F&K’s words). So they shift the zero point separating losses and gains to wherever the utility function looks most interesting! After doing this, they find “loss aversion”, ie the utility curve changes its slope at the transition between the loss side and the gain side. But since the transition was deliberately shifted to wherever the utility curve changed slope, this is almost tautological. It isn’t quite tautological: it’s interesting that most of the utility curves had a sharp transition zone, and it’s interesting that the transition was in the direction of loss-aversion rather than gain-seeking. But it’s tautological enough to be embarrassing. Still, this is Fishburn and Kochenberger’s embarrassment, not Kahneman and Tversky’s. And Fishburn and Kochenberger included this study in their review alongside several other studies that didn’t do this to the same degree. Kahneman and Tversky just cited the review article. I don’t think citing a review article that does weird things to a study really qualifies as “systematic misrepresentation.” I guess I’m having a hard time figuring out how angry to be, because everything about Fishburn and Kochenberger is terrible. The average study in F&K includes results from 5-10 executives. But the studies are pretty open about the fact that they interviewed more executives than this, threw away the ones who gave boring answers, and just published results from the interesting ones. Then they moved the axes to wherever looked most interesting. Then they used all this to draw sweeping generalizations about human behavior. Then F&K combined five studies that did this into a review article, without protesting any of it. And then K&T cited the review article, again without protesting. I have to imagine that all of this was normal by the standards of the time. I have looked up all these people and they were all esteemed scientists in their own day. And I believe the evidence shows K&T summarized F&K faithfully. Shouldn’t they have avoided citing F&K at all? Seems like the same kind of question as “Shouldn’t Pythagoras have published his theorem in a peer-reviewed journal, instead of moving to Italy, starting a cult, and exposing his thigh at the Olympic Games as part of a scheme to convince people he was the god Apollo?” Yes, but the past was a weird place. As best I can tell, K&T’s citation of G&P agrees with the authors’ own assessment of their results. Their citation of F&K agrees with the reviewers’ assessment and with a charitable reading of most of the studies involved, although those studies are terrible in many ways which are obvious to modern readers. I would urge people interested in the whodunit question to read Kahneman and Tversky’s original paper. I think it paints the picture of a team very interested in their own results and in theory, and citing other people only incidentally, and in accordance with the scientific standards of their time. I don’t feel a need to tar them as “misrepresenters”. III. Okay, But Is Loss Aversion Real? Remember, all that is about the personal deficiencies of Kahneman and Tversky. Realistically there have been hundreds of much better studies on loss aversion in the forty years since they wrote their article, so we should be looking at those. Here Hreha cites Gal & Rucker: The Loss Of Loss Aversion: Will It Loom Larger Than Its Gain? It’s a great 2018 paper that looks at recent evidence and concludes that loss aversion doesn’t exist. But it’s a very specific, interesting type of nonexistence, which I think the Hreha article fails to capture. G&R are happy to admit that in many, many cases, people behave in loss-averse ways, including most of the classic examples given by Kahneman and Tversky. They just think that this is because of other cognitive biases, not a specific cognitive bias called “loss aversion”. They especially emphasize Status Quo Bias and the Endowment Effect. Status Quo Bias is where you prefer inaction to action. Suppose you ask someone “Would you bet on a coin flip, where you get $60 if heads and lose $40 if tails?”. They say no. This deviates from rational expectations, and one way to think of this is loss aversion; the prospect of losing $40 feels “bigger” than the prospect of gaining $60. But another way to think of it is as a bias towards inaction - all else being equal, people prefer not to make bets, and you’d need a higher payoff to overcome their inertia. Endowment Effect is where you value something you already have more than something you don’t. Suppose someone would pay $5 to prevent their coffee mug from being taken away from them, but (in an alternative universe where they lack a coffee mug) would only pay $3 to buy one. You can think of this as loss aversion (the grief of losing a coffee mug feels “bigger” than the joy of gaining one). Or you can think of it as endowment (once you have the coffee mug, it’s yours and you feel like defending it). These are really fine distinctions; I had to read the section a few times before the difference between loss aversion and endowment effect really made sense to me. Kahneman and Tversky just sort of threw all all this stuff out and saw what stuck and didn’t necessarily try super hard to make sure none of the biases they discovered were entirely explainable as combinations of some of the others. G&R think maybe loss aversion is. They do some clever work setting up situations that test loss aversion but not status quo or endowment - for example, offering a risky bet vs. a safer bet. Here they find no evidence for loss aversion as a separate force from the other two biases. Somewhere in this process, they did an experiment where they gave participants a quarter minted in Denver and asked them if they wanted to exchange it for a quarter minted in Philadelphia. 60% of people very reasonably didn’t care, but another 35% had grown attached to their Denver quarter, with only 5% actively seeking the novelty of Philadelphia. Psychology is weird. I understand why some people would summarize this paper as “loss aversion doesn’t exist”. But it’s very different from “power posing doesn’t exist” or “stereotype threat doesn’t exist”, where it was found that the effect people were trying to study just didn’t happen, and all the studies saying it did were because of p-hacking or publication bias or something. People are very often averse to losses. This paper just argues that this isn’t caused by a specific “loss aversion” force. It’s caused by other forces which are not exactly loss aversion. We could compare it to centrifugal force in physics: real, but not fundamental. Also, you can’t use this paper to argue that “behavioral economics is dead”. At best, the paper proves that loss aversion is better explained by other behavioral economic concepts. But you can’t get rid of behavioral econ entirely! The stuff you have to explain is still there! It’s just a question of which parts of behavioral econ you use to explain it. Complicating this even further is Mrkva et al, Loss Aversion Has Moderators, But Reports Of Its Death Are Greatly Exaggerated (h/t Alex Imas, who has a great Twitter thread about this). This is an even newer paper, 2019, which argues that Gal and Rucker are wrong, and loss aversion does have an independent existence as a real force. There are many things to like about this paper. Previous criticisms of loss aversion argue that most experiments are performed on undergrads, who are so poor that even small amounts of money might have unusual emotional meaning. Mrkva collects a sample of thousands of millionaires (!) and demonstrates that they show loss aversion for sums of money as small as $20. On the other hand, I’m not sure they’re quite as careful as G&R at ruling out every other possible bias (although I don’t have a great understanding of where the borders between biases are and I can’t say this for sure). The main point I want to make is that all the scientists in this debate seem smart, thoughtful, and impressive. This isn’t like social priming experiments where one person says a crazy thing, nobody ever replicates it at scale, and as soon as someone tries the whole thing collapses. These have been replicated hundreds of times, with the remaining arguments being complicated semantic and philosophical ones about how to distinguish one theory from a very slightly different theory. If that takes replicating your result on a sample of thousands of millionaires, people will gather a sample of thousands of millionaires and get busy on the replication. Just overall really impressive work. I don’t feel qualified to take a side in the G&R vs. Mkrva debate, but both teams make me really happy that there are smart and careful people considering these questions. And this is just a drop in the bucket. Alex Imas also links Replicating patterns of prospect theory for decision under risk, which says: Though substantial evidence supports prospect theory, many presumed canonical theories have drawn scrutiny for recent replication failures. In response, we directly test the original methods in a multinational study (n = 4,098 participants, 19 countries, 13 languages), adjusting only for current and local currencies while requiring all participants to respond to all items. The results replicated for 94% of items, with some attenuation. Twelve of 13 theoretical contrasts replicated, with 100% replication in some countries. Heterogeneity between countries and intra-individual variation highlight meaningful avenues for future theorizing and applications. We conclude that the empirical foundations for prospect theory replicate beyond any reasonable thresholds. Beyond any reasonable thresholds! IV. Do Nudges Work? or, How Small Is Small? Continuing through the Hreha article: For a number of years, I've been beating the anti-nudge drum. Since 2011, I've been running behavioral experiments in the wild, and have always been struck by how weak nudges tend to be. In my experience, nudges usually fail to have *any* recognizable impact at all. This is supported by a paper that was recently published by a couple of researchers from UC Berkeley. They looked at the results of 126 randomized controlled trials run by two "nudge units" here in the United States. I want you to guess how large of an impact these nudges had on average... 30%? 20%? 10%? 5%? 3%? 1.5%? 1%? 0%? If you said 1.5%, you'd be right (the actual number is 1.4%, but if I had written that out you would have chosen it because of its specificity). According to the academic papers these nudges were based upon, these nudges should have had an average impact of 8.7%. But, as you probably understand by now, behavioral economics is not a particularly trustworthy field. I actually emailed the authors of this paper, and they thought the ~1% effect size of these interventions was something to be applauded—especially if the intervention was cheap & easy. Unfortunately, no intervention is truly cheap or easy. Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. Uber infamously had a team of behavioral economists working on its product, trying to “nudge” people in the right direction. Relatedly, Uber makes $10 billion in yearly revenue. If they can “nudge” people to spend 1% more, that’s $100 million. That’s not much relative to revenue, but it’s a lot in absolute terms. In particular, it pays the salary of a lot of behavioral economists. If you can hire 10 behavioral economists for $100,000 a year and make $100 million, that’s $99 million in profit. Or what if you’re a government agency, trying to nudge people to do prosocial things? There are about 90 million eligible Americans who haven’t gotten their COVID vaccine, and although some of them are hard-core conspiracy theorists, others are just lazy or nervous or feel safe already. (source) Whoever decided on that grocery gift card scheme was nudging, whether or not they have an economics degree - and apparently they were pretty good at it. If some sort of behavioral econ campaign can convince 1.5% of those 90 million Americans to get their vaccines, that’s 1.4 million more vaccinations and, under reasonable assumptions, maybe a few thousand lives saved. Hreha says that: Every single intervention requires, at the very minimum, administrative overhead. If you're going to do something, you need someone (or some system) to implement and keep track of it. If an intervention is only going to get you a 1% improvement, it's probably not even worth it. This depends on scale! 1% of a small number isn’t worth it! 1% of a big number is very worth it, especially if that big number is a number of lives! A few caveats. First, a small number only matters if it’s real. It’s very easy to get spurious small effects, so much so that any time you see a small effect you should wonder if it’s real. I’m ready to be forgiving here because behavioral economics is so well-replicated and common-sensically true, but I wouldn’t blame anyone who steers clear. Second, Hreha says: To be honest, you can probably use your creativity to brainstorm an idea that will get you a 3-4% minimum gain, no behavioral economics "science" required. Which leads me to the final point I'd like to make: rules and generalizations are overrated. The reason that fields like behavioral economics are so seductive is because they promise people easy, cookie-cutter solutions to complicated problems. Figuring out how to increase sales of your product is hard. You need to figure out which variables are responsible for the lackluster interest. Is the price the issue? Is the product too hard to use? Is the design tacky? Is the sales organization incompetent? Is the refund/return policy lacking? etc. Exploring these questions can take months (or years) of hard work, and there's no guarantee that you'll succeed. If, however, a behavioral economist tells you that there are nudges that will increase your sales by 10%, 20%, or 30% without much effort on your part... Whoa. That's pretty cool. It's salvation. Thus, it's no surprise that governments and companies have spent hundreds of millions of dollars on behavioral "nudge" units. Unfortunately, as we've seen, these nudges are woefully ineffective. Specific problems require specific solutions. They don't require boilerplate solutions based on general principles that someone discovered by studying a bunch of 19 year old college students. However, the social sciences have done a good job of convincing people that general principles are better solutions for problems than creative, situation-specific solutions. In my experience, creative solutions that are tailor-made for the situation at hand *always* perform better than generic solutions based on one study or another. Hreha is a professional in this field, so presumably he’s right. Still, compare to medicine. A thoughtful doctor who tailors treatment to a particular patient sounds better (and is better) than one who says “Depression? Take this one all-purpose depression treatment which is the first thing I saw when I typed ‘depression’ into UpToDate”. But you still need medical journals. Having some idea of general-purpose laws is what gives the people making creative solutions something to build upon. (also, at some point your customers might want to check your creative solution to see whether it actually gives a “3-4% minimum gain, no behavioral economics required”, and that would be at least vaguely study-shaped.) Third, everyone who said nudging had vast effects is still bad and wrong. Many of them were bad and wrong and making fortunes consulting for companies about how to implement the policies they were claiming were super-powerful. This is suspicious and we should lower our opinion of them accordingly. In a previous discussion of growth mindset, I wrote: Imagine I claimed our next-door neighbor was a billionaire oil sheik who kept thousands of boxes of gold and diamonds hidden in his basement. Later we meet the neighbor, and he is the manager of a small bookstore and has a salary 10% above the US average... Should we describe this as “we have confirmed the Wealthy Neighbor Hypothesis, though the effect size was smaller than expected”? Or as “I made up a completely crazy story, and in unrelated news there was an irrelevant deviation from literally-zero in the same space”? All the people talking about oil sheiks deserve to get asked some really uncomfortable questions. And a lot of these will be the most famous researchers - the Dan Arielys of the world - because of course the people who successfully hyped their results a lot are the ones the public knows about. Still, the neighbor seems like a neat guy, and maybe he’ll give you a job at his bookstore. V. Conclusion: Musings On The Identifiable Victim Effect I actually skipped the very beginning of Hreha’s article. I want to come back to it now. It begins: The last few years have been particularly bad for behavioral economics. A number of frequently cited findings have failed to replicate. Here are a couple of high profile examples: The Identifiable Victim Effect (featured in the workbooks I wrote with Dan Ariely and Kristen Berman in 2014)
April 22, 2025 · Original source
6: Why did Doordash win? Now that I think about it, I haven’t heard much from GrubHub or UberEats lately. The article speculates that DoorDash started with some good strategic choices (organizing their own delivery fleet, starting in suburbs), then executed better than their competitors.
Huawei

Huawei is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 26, 2025 and February 25, 2026. The archive places it in contexts such as "the government will make Huawei sell at minimal profit margins"; "useful it is in dealing with Huawei". It most often appears alongside Anthropic, Claude, Dean Ball.

Article page
Huawei
Mention count
2
Issue count
2
First seen
November 26, 2025
Last seen
February 25, 2026
November 26, 2025 · Original source
Future developments may threaten these people’s China hawkery even further. NVIDIA has a 90% profit margin on every advanced chip sold in the US. China is still working on developing advanced chips, but once they get them, the government will make Huawei sell at minimal profit margins, to support the national interest of winning the AI race. That means that at technological parity, US chips will cost 10x Chinese chips, and it may become a live topic of debate whether the US government should force NVIDIA to cut its own profit margins. I can only vaguely predict who will take which side of these debate, but I bet it won’t line up with current levels of China hawkery.
February 25, 2026 · Original source
the nuclear option, designating Anthropic a “supply chain risk”. This would ban US companies that use Anthropic products from doing business with the military2. Since many companies do some business with the military, this would lock Anthropic out of large parts of the corporate world and be potentially fatal to their business3. The “supply chain risk” designation has previously only been used for foreign companies like Huawei that we think are using their connections to spy on or implant malware in American infrastructure. Using it as a bargaining chip to threaten a domestic company in contract negotiations is unprecedented.
Isn’t Hegseth just doing his job of trying to ensure the military has the best weapons possible? The idea of declaring a US company to be a foreign adversary, potentially destroying it, just because it’s not allowing the Pentagon to unilaterally renegotiate its contract is not normal practice. It’s insane Third World bullshit that nobody would have considered within the Overton Window a week ago. It will rightly chill investment in the US, make future companies scared to contract with the Pentagon (lest the Pentagon unilaterally renegotiate their contracts too), and give the Trump administration a no-legal-review-necessary way to destroy any American company that they dislike for any reason. Probably the mere fact that a government official has considered this option is reason to take the “supply chain risk” law off the books, no matter how useful it is in dealing with Huawei etc, since the government has proven it can’t use it responsibly. Every American company ought to be screaming bloody murder about this. If they aren’t, it’s because they’re too scared they’ll be next.
Huel

Huel is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 20, 2025 and January 16, 2026. The archive places it in contexts such as "bottles of Huel"; "an intern who came once a week to bring him whiteboards, markers, and bottles of Huel"; "a frustrated groping towards meal replacements like Soylent or Huel". It most often appears alongside Elon Musk, MAGA, Adams.

Article page
Huel
Mention count
2
Issue count
2
First seen
February 20, 2025
Last seen
January 16, 2026
February 20, 2025 · Original source
St. Promentius shut himself in an eremite’s cell and vowed not to leave until he had figured out the secrets of AI corrigibility. He stayed in the cell for nine years, speaking to nobody except an intern who came once a week to bring him whiteboards, markers, and bottles of Huel. At the end of nine years, the intern told him that the city planned to build an apartment tower over his cell. St. Promentius refused to break his vow and leave the cell. But he also refused his intern’s offer to inform the city of his presence, saying that “he who delays a building for any reason shall be judged with the NIMBYs”. His cell was demolished during the construction and it is assumed that he died, although others say that he only sleeps within the masonry, and will return during Crunch Time.
January 16, 2026 · Original source
Okay, “I am cleverer than everyone else”, got it. His next venture (c. 1999) was the Dilberito, an attempt to revolutionize food via a Dilbert-themed burrito with the full Recommended Daily Allowance of twenty-three vitamins. I swear I am not making this up. A contemporaneous NYT review said it “could have been designed only by a food technologist or by someone who eats lunch without much thought to taste”. The Onion, in its twenty year retrospective for the doomed comestible, called it a frustrated groping towards meal replacements like Soylent or Huel, long before the existence of a culture nerdy enough to support them. Adams himself, looking back from several years’ distance, was even more scathing: “the mineral fortification was hard to disguise, and because of the veggie and legume content, three bites of the Dilberito made you fart so hard your intestines formed a tail.”
hydroxychloroquine

hydroxychloroquine is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 17, 2021 and December 22, 2021. The archive places it in contexts such as "Group B got hydroxychloroquine"; "ibvermectin plus hydroxychloroquine"; "all the hype about ivermectin and hydroxychloroquine". It most often appears alongside COVID, ivermectin, ivermectin.

Article page
hydroxychloroquine
Mention count
2
Issue count
2
First seen
November 17, 2021
Last seen
December 22, 2021
November 17, 2021 · Original source
Click to expand. # is how many people were in the smallest relevant group (eg if there were 20 people in placebo and 10 in ivermectin, it was 10). Dose is ivermectin dose x number of days. Tested w/ is what drugs were given alongside ivermectin; compare is what drugs were in the “placebo” group (I excluded some very common things like paracetamol). %-PCR7 is what percent of patients had a negative PCR test (indicating recovery) after 7 days (though if 7 wasn’t available, I accepted anything from 6-12); the (I) and (P) are ivermectin and placebo groups. R is the ratio - green if statistically significant, red otherwise. DaysPCR is how many days it took to get a negative PCR test. Days to -sym are how many days it took symptoms to resolve. -outc is some serious negative outcome in the study, either clinical worsening, hospitalization, or death. I was inconsistent which one I chose, trying to pick whichever I thought struck a balance between high sample size and severity. Since this was almost never significant, I made it blue if it favored ivermectin and orange if it favored placebo (which it never did; there is no orange). Lowest p is the lowest p-value in the study for one of the headline results. 1o+ is whether the primary outcome was positive or not. I made this very quickly and unprincipledly and I am sure there are a lot of errors; please forgive me. Of studies that included any of the endpoints I recorded, ivermectin had a statistically significant effect on the endpoint 13 times, and failed to reach significance 8 times. Of studies that named a specific primary endpoint, 9 found ivermectin affected it significantly, and 12 found it didn’t. But that’s still pretty good. And “doesn’t affect to a statistically significant degree” doesn’t mean it doesn’t work. It might just mean your study is too small for a real and important effect to achieve statistical significance. That’s why people do meta-analyses to combine studies. And the ivmmeta people say they did that and it was really impressive. All of this is still basically what things would look like if ivermectin worked. But of course we can’t give every study one vote. We’ve got to actually look at these and see which ones are good and which ones are bad. So, God help us, let’s go over all thirty of the ivermectin studies in this top panel of ivmmeta.com. (if you get bored of this, scroll down to the section called “The Analysis”) The Studies Elgazzar et al: This one isn’t on the table above, but we can’t start talking about the others until we get it out of the way. 600 Egyptian patients were randomized into six groups, including three that got ivermectin. The ivermectin groups did substantially better: for example, 2 vs. 20 deaths in ivermectin group 3 vs. non-ivermectin group 4. There were various other equally impressive outcomes. Unfortunately, it’s all false. Some epidemiologists and reporters were able to obtain the raw data (it was password-protected, but the password was “1234”), and it was pretty bizarre. Some patients appeared to have died before the trial started; others were arranged in groups of four such that it seemed like the authors had just copy-pasted the same four patients again and again. Probably either the study never happened, or at least the data were heavily edited afterwards. You can read more here. A lot of the apparent benefit of ivermectin in meta-analyses disappeared after taking out this paper (though remember, this isn’t even on the table at the top of the post, so it doesn’t directly affect that). Since the Elgazzar debacle, a group of researchers including Gideon Meyerowitz-Katz, Kyle Sheldrake, James Heathers, Nick Brown, Jack Lawrence, etc, have been trying to double-check as many other ivermectin studies as possible. At least three others - Samaha, Carvallo, and Niaee - have similar problems and have been retracted. Those studies were all removed before I screenshotted the table above, and they’re not on there. But everybody is pretty paranoid right now and looking for fraud a lot harder than they might be in normal situations. Moving on: Chowdury et al: Bangladeshi RCT. 60 patients in Group A got low-dose ivermectin plus the antibiotic doxycycline, 56 in Group B got hydroxychloroquine (another weird COVID treatment which most scientists think doesn’t work) plus the antibiotic azithromycin. No declared primary outcome. Ivermectin group got to negative PCR a little faster than the other (5.9 vs. 7 days) but it wasn’t statistically significant (p = 0.2). A couple of other non-statistically-significant things happened too. 2 controls were hospitalized, 0 ivermectin patients were. This is a boring study that got boring results, so nobody has felt the need to assassinate it, but if they did, it would probably focus on both groups getting various medications besides ivermectin. None of these other medications are believed to work, so I don’t really care about this, but you could tell a story where actually doxycycline works great at addressing associated bacterial pneumonias, or where HCQ causes lots of side effects and that makes the ivermectin group look good in comparison, or whatever. Espitia-Hernandez et al: Mexican trial which is probably not an RCT - all it says is that “patients were voluntarily allocated”. 28 ended up taking a cocktail of low-dose ivermectin, vitamin D, and azithromycin; 7 were controls. On day ten, everyone (!) in the experimental group was PCR negative; everyone (!) in the control group was still positive. Also, symptoms in the experimental group lasted an average of three days; in the control group, more like 10. These results make ivermectin look amazingly super-good, probably better than any other drug for any other disease, except maybe stuff like vitamins for treatment of vitamin deficiency. Any issues? We don’t know how patients were allocated, but they discuss patient characteristics and they don’t look different enough to produce this big an effect size. The experimental group got a lot of things other than ivermectin, but I would be equally surprised if vitamin D or azithromycin cured COVID this effectively. It deviated from its preregistration in basically every way possible, but you shouldn’t be able to get “every experimental patient tested negative when zero control patients did” by garden-of-forking-paths alone! But this has to be false, right? Even the other pro-ivermectin studies don’t show effects nearly this big. In all other studies combined, ivermectin patients took an average of 8 days to recover; in Espitia-Hernandez, they took 3. Also, it’s pretty weird that the entire control group had positive PCRs on day 10 - in most other studies, a majority of people had negative PCRs by day 7 or so, regardless of whether they were control or placebo. Everything about this is so shoddy that I can easily believe something went wrong here. I don’t have a great understanding of this one but I don’t trust it at all. Luckily it is small and non-randomized so it will be easy to ignore going forward. I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
December 22, 2021 · Original source
In the midst of all the hype about ivermectin and hydroxychloroquine, scientists put together the giant 4,000-person TOGETHER trial, intended to test all these exciting COVID early treatments. You know what happened next: ivermectin and hydroxychloroquine crashed and burned.
IBM

IBM is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 22, 2022 and December 04, 2024. The archive places it in contexts such as "When IBM got sick of antitrust fights"; "a sort of “nobody ever got fired for buying IBM” type of standard". It most often appears alongside 3D printing, Abercrombie & Fitch, Adam Neumann.

Article page
IBM
Mention count
2
Issue count
2
First seen
September 22, 2022
Last seen
December 04, 2024
September 22, 2022 · Original source
The last big antitrust case involved Microsoft. When IBM got sick of antitrust fights, they decided to outsource the operating system for their PCs. This was like throwing a monopoly bouquet at a wedding and Bill Gates was the bridesmaid who jumped highest and snatched the prize. His plan was to leverage this operating system monopoly into an internet monopoly, and the scheme was working before the Clinton administration sued. The reason I am writing this on Substack and not some Microsoft comment board is because of an antitrust lawsuit.
December 04, 2024 · Original source
One clue is that not everywhere went modern at the same rate. The average suburban house is still built in traditional styles, because home-buyers have no need to justify them to anyone but themselves. But corporations and governments have a more complicated mandate. When executive or bureaucrats make decisions, they’re supposed to be catering to more than their personal aesthetic taste. They’re supposed to be following best practices and doing what’s responsible, maybe as judged by a sort of “nobody ever got fired for buying IBM” type of standard. In architecture, the responsible-person standard was for big institutions that needed buildings to convene a Selection Committee including some representatives of the institution and at least one prestigious architect. But the representatives of the institution were out of their depth, and the prestigious architect could usually bully them into submission. So modernism it was.
Ikea

Ikea is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 07, 2021 and November 03, 2023. The archive places it in contexts such as "Ikea comes from Denmark"; "grudgingly accepting reality and buying IKEA". It most often appears alongside 23andme, ABBA, ACX Grants.

Article page
Ikea
Mention count
2
Issue count
2
First seen
July 07, 2021
Last seen
November 03, 2023
July 07, 2021 · Original source
All of this gets really confusing and I think everyone on all sides of this debate should agree to just never mention Sweden again. Not just with respect to coronavirus policy. At all. If anyone asks, there are only two Scandinavian countries, Ikea comes from Denmark, and ABBA was just a weird dream. In conclusion, the weaker Swedish lockdown in the early phase of the pandemic probably increased the death rate by a factor of two (using other European countries as a counterfactual/control) to five (using other Scandinavian countries as a counterfactual/control). These people investigate this question more formally and find something similar. These changes in death rate mean the policy caused an extra 1,000 to 3,000 deaths in the early phase of the pandemic. There was probably less effect in the later phases of the pandemic because Sweden’s lockdown policy was closer to everyone else’s.
November 03, 2023 · Original source
If all of this is too ambitious, come up with a roadmap for how to start with small achievable victories and build up to cathedrals and concert halls. For example, maybe we should start by getting someone to produce the sort of Art Nouveau furniture everyone wistfully lists on their Pinterest before grudgingly accepting reality and buying IKEA. If that works, we can leverage what we’ve learned and the publicity we’ve gained to start working on bigger targets.
Illumina

Illumina is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 01, 2022 and July 03, 2025. The archive places it in contexts such as "Illumina’s suspected-of-being-sinister monopoly on sequencing"; "Illumina short-read sequencing/SNP panels have been the major source of data"; "TOPMED dataset, which is from Illumina short reads". It most often appears alongside Wikipedia, 23andme, @a_centrism.

Article page
Illumina
Mention count
2
Issue count
2
First seen
July 01, 2022
Last seen
July 03, 2025
July 01, 2022 · Original source
34: New-ish startup Ultima Genomics claims to have lowered full genome sequencing costs by an order of magnitude, to $100/genome (and incidentally to have broken Illumina’s suspected-of-being-sinister monopoly on sequencing). Here’s some fair criticism, but overall I find this exciting.
July 03, 2025 · Original source
Sequencing technology doesn't get discussed nearly enough in this area. Illumina short-read sequencing/SNP panels have been the major source of data for all of these studies, and they are absolutely delightful at finding SNPs but are crap at anything else. I think it will be appreciated that generally things that impact function aren't SNPs, they are broad changes, and so much human genomics seems to be hoping that the thing that is contributing to a change is able to spotted by being close to a SNP, instead of actually looking at the thing that is causing the change.
Genomes aren't lists of SNPs, they are mostly repeats and 2x150bp isn't going to get anywhere near close to capturing that variation, no matter how 'deep' you sequence. Long-read sequencing (PacBio & ONT, not Illumina's synthetic tech) is clearly better, and continues to demonstrate that there is massive variation that is easy to see when you have a bunch of 20kbp fragment, while almost impossible when you're just aligning little chunks of text to a 3gbp genome.
I work in non-model genomics and long-read sequencing is such a clear winner I keep getting surprised when Illumina gets contracts for these massive human studies. The Human Pangenome Consortium is going to be providing a dataset that is way more useful than anything that's come before. Anecdotally, I hear that for some non-European genomic data they know that ~10% of the data from an individual DOESN'T EVEN MAP to the human reference (but is human genomic data). This is all invisible to analysis, or even worse, just confounds things, as the 'true' causal SNP is somewhere in the data that doesn't get analysed, and so we're stuck looking at noise and trying to make sense of it.
Instacart

Instacart is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 04, 2024 and January 11, 2024. The archive places it in contexts such as "the next Instacart has a 6% RoI"; "He chooses Instacart as his exemplar of capitalism"; "investing $1M in Instacart means "you can give 2,000 people a great deal on grocery delivery."". It most often appears alongside ACX Grants, capitalism, Charter Cities Institute.

Article page
Instacart
Mention count
2
Issue count
2
First seen
January 04, 2024
Last seen
January 11, 2024
January 04, 2024 · Original source
Do something like donating to charity, but the donation should go to charities that promote capitalism somehow, or be an investment in companies doing charitable things (impact investing) I agree that overall capitalism has produced more good things than charity. But when I try to think at the margin, in Near Mode, I can’t make this argument hang together. Here’s my basic objection: Consider some company. I’m going to pick Instacart, because I like it and use it often. Instacart is like Uber for groceries. It delivers them to your house, so you don’t have to go shopping. It’s great if you’re lazy, or if you’re sick and don’t want to leave the house. I’m not putting my finger on the scales by choosing Instacart here. Instacart is great. Instacart makes yearly profit of $500 million, yearly revenue of $2.5 billion, and has 10 million yearly customers (who I guess pay $250 each per year?) and a market cap of $10 billion. For complicated reasons I’ll relegate to a footnote1, I’m going to summarize the deal that Capitalism offers by allowing Instacart to exist to “For $1 million, you can give 2,000 people a great deal on grocery delivery”. Compare this to a good charity, like GiveWell’s pick Dispensers For Safe Water. If I understand their claim right, per $1 million they can give 50,000 people clean water for ten years, which would probably save about 1,500 lives. So which is a better use of $1 million? Give it to Capitalism, and give 2,000 people a great deal on grocery delivery? Or give it to Charity, and give 50,000 people clean water and save 1,500 lives? Even without being able to exactly quantify the value of grocery delivery deals vs. clean water, common-sensically Charity wins on first-order effects. So the argument for Capitalism must go through something about second-order effects. But what are these? I can think of a few possibilities: Job creation: Along with helping its customers, Instacart employs 10,000 full-time employees and 600,000 gig workers, so our $1 million investment might produce a few dozen jobs. That still doesn’t seem to counterbalance the advantage of Charity. But also (and I admit I have trouble thinking about this), it doesn’t seem obvious that Instacart “causes” jobs. Suppose Instacart had never been founded. Then people would spend whatever money they now spend on Instacart on something else (let’s say booze and porn), which would also create jobs (for brewers, bartenders, and porn stars). There’s no particular reason to think spending the money on Instacart creates more jobs than spending it on those other things would. So how many jobs does Instacart create over replacement? I’m not sure but I think it must be much less than the official number of employees.
Job creation: Along with helping its customers, Instacart employs 10,000 full-time employees and 600,000 gig workers, so our $1 million investment might produce a few dozen jobs. That still doesn’t seem to counterbalance the advantage of Charity. But also (and I admit I have trouble thinking about this), it doesn’t seem obvious that Instacart “causes” jobs. Suppose Instacart had never been founded. Then people would spend whatever money they now spend on Instacart on something else (let’s say booze and porn), which would also create jobs (for brewers, bartenders, and porn stars). There’s no particular reason to think spending the money on Instacart creates more jobs than spending it on those other things would. So how many jobs does Instacart create over replacement? I’m not sure but I think it must be much less than the official number of employees.
Replaceability: I actually think this one favors Charity. If nobody had invested in Instacart, surely “grocery delivery” wouldn’t remain an unfilled niche forever. But there’s lots of room for more money in Dispensers For Safe Water, and I think any money you don’t send to them simply won’t be spent on water dispensing.
January 11, 2024 · Original source
He never really addresses why plugging the cash into an index like the S&P 500 isn't a better use of funds than GiveWell's recommended charity. He chooses Instacart as his exemplar of capitalism, but then concludes that investing $1M in Instacart means "you can give 2,000 people a great deal on grocery delivery." But the whole point of investing is that it isn't one-and-done, that instead it grows exponentially over the long term, building wealth in the form of new and better companies which provide products, services, innovation and technology that are responsible for basically all of the good things you see on Steven Pinker's up-and-to-the-right charts illustrating the improvement of the human condition over time. These are the things that, if all goes well, will eventually lift humanity to the heavens, slay the demons (disease, death, etc.) that have haunted us forever, and awaken the dead matter of the cosmos into flourishing sentience.
Second, I care a lot about marginal utility of money. I think a (consumption) dollar goes much further in the developing world than the developed world. If you invest in high-growth companies, it may create more total wealth, but most of that wealth stays in the developed world. If you donate to charity, you will create less numerical wealth, but it will go to people who need it more. Which matters more? This is what the Instacart vs. clean water example was meant to provide intuitions for.
Third, how does company wealth compound vs. philanthropic “wealth”? If you give your money to a company, they’ll expand operations and grow at some rate (on average the market rate of return). If you spend your money curing tropical diseases, then some people will survive, and those people will build wealth / do labor / grow the economy (also you’ll save money that would otherwise have been spent treating those diseases). As I said on the subreddit, whatever else is bad about an 18 year old dying, you've lost ~50 years worth of productive labor that you invested eighteen years building up. Once you consider how much human effort it took raise and educate 2,000 eighteen-year-olds, and how much you can get done with a 2,000-person labor force, then letting those 2,000 people die starts to feel like a giant economic waste even in addition to the humanitarian cost (not to mention the amount of money saved by not building hospitals to treat the diseases that would otherwise have killed them). Probably those 2,000 people don't create more compounding wealth than an investment of the same amount of money into Instacart would, but I think the diminishing marginal utility of money case makes it likely that they produce more utility-adjusted wealth.
liraglutide

liraglutide is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 30, 2022 and March 12, 2025. The archive places it in contexts such as "Saxenda (liraglutide) for weight loss"; "Liraglutide (Victoza®, Saxenda®)". It most often appears alongside Eli Lilly, FDA, Novo Nordisk.

Article page
liraglutide
Mention count
2
Issue count
2
First seen
November 30, 2022
Last seen
March 12, 2025
November 30, 2022 · Original source
First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.
March 12, 2025 · Original source
Liraglutide (Victoza®, Saxenda®)
Liraglutide (Victoza®, Saxenda®) …but liraglutide is noticeably worse than the others, and most people prefer either semaglutide or tirzepatide. These cost about $1000/month and are rarely covered by insurance, putting them out of reach for most Americans. …if you buy them from the pharma companies, like a chump. For the past three years, there’s been a shortage of these drugs. FDA regulations say that during a shortage, it’s semi-legal for compounding pharmacies to provide medications without getting the patent-holders’ permission. In practice, that means they get cheap peptides from China, do some minimal safety testing in house, and sell them online. So for the past three years, telehealth startups working with compounding pharmacies have sold these drugs for about $200/month. Over two million Americans have made use of this loophole to get weight loss drugs for cheap. But there was always a looming question - what happens when the shortage ends? Many people have to stay on GLP-1 drugs permanently, or else they risk regaining their lost weight. But many can’t afford $1000/month. What happens to them? Now we’ll find out. At the end of last year, the FDA declared the shortage over. The compounding pharmacies appealed the decision, but the FDA recently confirmed its decision is final. As of March 19 (for tirzepatide) and April 22 (for semaglutide), compounding pharmacies can no longer sell cheap GLP-1 drugs. Let’s take a second to think of the real victims here: telehealth company stockholders. Some compounding pharmacies are already telling their customers to look elsewhere, but not everyone is going gently into the good night. I’m seeing telehealth companies float absolutely amazing medicolegal theories, like: Compounding pharmacies are allowed to provide patients with a drug if they can’t tolerate the commercially available doses and need a special compounding dose. Perhaps our patients who were previously on semaglutide 0.5 mg now need, uh, semaglutide 0.51 mg. In fact, they need exactly 0.51 mg or they’ll die! Since the pharma companies don’t make 0.51 mg doses, it has to be compounded and we can still sell it.
Lundbeck

Lundbeck is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 18, 2022 and May 31, 2023. The archive places it in contexts such as "gotten money from Lundbeck"; "a Danish team affiliated with the pharma company Lundbeck discovered an entirely new way to get into fights about this". It most often appears alongside benzodiazepines, ADHD, Angelini.

Article page
Lundbeck
Mention count
2
Issue count
2
First seen
May 18, 2022
Last seen
May 31, 2023
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
May 31, 2023 · Original source
Recently a Danish team affiliated with the pharma company Lundbeck discovered an entirely new way to get into fights about this. I found their paper, Determining maximal achievable effect sizes of antidepressant therapies in placebo-controlled trials, more enlightening than most other writing on this issue. They ask: what if the skeptics’ preferred effect size number is impossible to reach?
Luvox

Luvox is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 22, 2021 and December 22, 2021. The archive places it in contexts such as "get the FDA to approve Luvox for COVID"; "Here’s my pitch for fluvoxamine (Luvox) for COVID"; "the risk from adding a few extra Luvox prescriptions for COVID is still much less". It most often appears alongside budesonide, FDA, fluvoxamine.

Article page
Luvox
Mention count
2
Issue count
2
First seen
December 22, 2021
Last seen
December 22, 2021
December 22, 2021 · Original source
Here’s my pitch for fluvoxamine (Luvox) for COVID.
But a different drug, the SSRI antidepressant fluvoxamine, actually did really well! It decreased COVID hospitalizations by about 30% - not the perfect cure rate the rumors attributed to ivermectin, but a substantial decrease. Given the size and professionalism of this study, and another smaller one that also got positive results, I and many others take Luvox pretty seriously. At this point I’d give it 60-40 it works.
What are the risks? Like every medication, including Tylenol, aspirin, etc, Luvox has some common minor side effects and some rare major ones. But let’s step back a second. Fluvoxamine is a bog-standard SSRI. Its side effects are generic SSRI side effects. We give SSRIs to 30 million people a year, or about 10% of all Americans. As a psychiatrist, I’m not supposed to say flippant things like “we give SSRIs out like candy”. We do careful risk-benefit analysis and when appropriate we screen patients for various risk factors. But after we do all that stuff, we give them to 10% of Americans, compared to 12% of Americans who got candy last Halloween. So you can draw your own conclusion about how severe we think the risks are.
December 22, 2021 · Original source
In my post yesterday, I quoted a Vox article describing work by Dr. Ed Mills and others to get the FDA to approve Luvox for COVID. As of that point, the FDA didn’t know how to process an application without a sponsoring drug company:
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
But it looks like just as I published, he and his colleagues found a way around the problem: #IDTwitter we submitted EUA Application for #Fluvoxamine for #COVID19 to @US_FDA with the assistance of @EricLenze2 @AngelaReiersen @drklausner @ShohamTxID, and Ed Mills \nIf you want to sign a letter of support forms.gle/3mDgxxgMgtVDNS…\n(names are not public &amp; will be reviewed) ","username":"boulware_dr","name":"David Boulware, MD MPH","profile_image_url":"","date":"Tue Dec 21 21:14:24 +0000 2021","photos":[],"quoted_tweet":{"full_text":"#IDTwitter For those in the medical community who would want to sign on to a letter of support for @US_FDA EUA Application for #Fluvoxamine please go here: https://t.co/7K0OCSSm3O \n\n(I ask others to not spam this, as this creates more work for me in reviewing the list).","username":"boulware_dr","name":"David Boulware, MD MPH"},"reply_count":0,"retweet_count":36,"like_count":122,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":false}" data-component-name="Twitter2ToDOM"> …though so far I’m having trouble figuring out their exact strategy:
Magic: the Gathering

Magic: the Gathering is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 16, 2021 and December 31, 2025. The archive places it in contexts such as "Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp"; "head designer of Magic: the Gathering". It most often appears alongside capitalism, China, Germany.

Mention count
2
Issue count
2
First seen
April 16, 2021
Last seen
December 31, 2025
April 16, 2021 · Original source
By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
December 31, 2025 · Original source
“Players are great at identifying problems but terrible at coming up with solutions.” This is from Mark Rosewater, the head designer of Magic: the Gathering. His point is that when playing a game, it’s easy to tell that you aren’t having fun, but not always so easy to know exactly why or how to fix it. And in my experience, it’s very true--people will repeat platitudes they’ve heard from others about what makes a game fun or not fun, but the complaint manifestly does not apply to the situation they’re describing. Or there’s another situation which totally resolves the complaint but they’re still not having fun.
match.com

match.com is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 05, 2022 and February 14, 2023. The archive places it in contexts such as "the founder of match.com"; "then Match.com bought it, murdered it, and gutted the corpse". It most often appears alongside OKCupid, abundance liberalism, Aella.

Article page
match.com
Mention count
2
Issue count
2
First seen
November 05, 2022
Last seen
February 14, 2023
November 05, 2022 · Original source
Apparently our incumbent representative on the Santa Clara Valley Water District is the founder of match.com?? I feel like I have to vote against him because I'm still mad about OKCupid.
But in case that isn’t enough for you, said match.com founder - Gary Kremen - is also accused of “bullying” and “mistreating” workers and creating a “culture of fear” at the water district. He is additionally accused of sending unsolicited nude photos to employees and of “deceiving voters” in order to extend his term limits.
February 14, 2023 · Original source
Somehow this never happens. OKCupid managed it for a few years, and then Match.com bought it, murdered it, and gutted the corpse. Now it’s just a wasteland of Tinder clones, forever. Sure, Luna’s rectification of the financial incentives is clever, but it seems like there’s been some kind of more fundamental failure. Why can’t we have the normal low-tech version? Why are things so bad that the people I know have been reduced to manually making profiles on Google Docs and listing them on an online spreadsheet?
(I’m not making up these examples - the site for clowns is here, communists here, cowboys here)
McDonald's

McDonald's is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 07, 2023 and March 25, 2025. The archive places it in contexts such as "National franchise stores, such as McDonald’s, Hardee’s, and Kentucky Fried Chicken"; "in front of McDonalds". It most often appears alongside Iowa, Japan, South Korea.

Article page
McDonald's
Mention count
2
Issue count
2
First seen
June 07, 2023
Last seen
March 25, 2025
June 07, 2023 · Original source
No direct inline source block was recovered for this mention.
March 25, 2025 · Original source
Contact: David Reis Contact Info: davidreis[a t]gmail[period]com Time: Saturday, April 12th, 04:00 PM Location: Diamond Mall 1rst Floor Food Court, in front of McDonalds. Address Av. Olegário Maciel, 1600 Coordinates: https://plus.codes/58GR33C3+R4J Group Link: https://chat.whatsapp.com/C0S [remove this bit] Ze8fdU8O1WgLd4GsST6
McDonald’s

McDonald’s is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 07, 2023 and September 12, 2025. The archive places it in contexts such as "es, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken"; "I was McDonald’s biggest money maker". It most often appears alongside 747, A Change of Heart, Abraham.

Article page
McDonald’s
Mention count
2
Issue count
2
First seen
June 07, 2023
Last seen
September 12, 2025
June 07, 2023 · Original source
The two parties are the most willing to have others fight under their banner. You can do whatever you want as long as you play under my banner and negotiate certain terms. National franchise stores, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken, are available nationwide. The head office has no idea what they are doing other than selling the same goods. Americans implement the same ideas in politics and economics. The two parties are like a National franchise, with each branch doing its own thing to sell its products. . . It is sometimes unbelievable that two major parties that can dominate politics are so loosely organized.
September 12, 2025 · Original source
“I hate meat now. I can’t stand it. I was McDonald’s biggest money maker, and now meat makes me throw up. Actually, when I even smell it, my heart starts to race.”
Metamask

Metamask is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 22, 2021 and November 07, 2024. The archive places it in contexts such as "There’s also apparently an easier way with a Metamask wallet"; "a Metamask wallet". It most often appears alongside Coinbase, Metaculus, Polymarket.

Article page
Metamask
Mention count
2
Issue count
2
First seen
June 22, 2021
Last seen
November 07, 2024
June 22, 2021 · Original source
I’m happy to report that getting money into Polymarket has gone from impossible to merely annoying. Non-Americans can apparently do it directly with a credit card; Americans will have to send USDC, separately send Ethereum to a different address to cover transaction fees, then wait ~10 minutes for everything to percolate through. My level of crypto knowledge is “can use Coinbase” and I was able to figure it out. There’s also apparently an easier way with a Metamask wallet, which I didn’t try.
November 07, 2024 · Original source
Why not? In order for an American to use Polymarket, you have to get a VPN, a Coinbase account, and a Metamask wallet, use the VPN, get crypto on the Coinbase account, transfer it to the Metamask wallet, connect the Metamask wallet to Polymarket, and buy the shares you want. Ability to do this rules out 99% of the US population.
molnupiravir

molnupiravir is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 22, 2021 and December 22, 2021. The archive places it in contexts such as "evidence for molnupiravir is in many ways weaker than fluvoxamine"; "communications about Merck’s drug molnupiravir". It most often appears alongside budesonide, FDA, fluvoxamine.

Article page
molnupiravir
Mention count
2
Issue count
2
First seen
December 22, 2021
Last seen
December 22, 2021
December 22, 2021 · Original source
But according to Kelsey Piper at Vox, that’s where they are right now:
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
December 22, 2021 · Original source
In my post yesterday, I quoted a Vox article describing work by Dr. Ed Mills and others to get the FDA to approve Luvox for COVID. As of that point, the FDA didn’t know how to process an application without a sponsoring drug company:
[Professor Ed] Mills, who thinks that fluvoxamine and budesonide are both appropriate to prescribe to patients sick with Covid-19, compares public messaging on fluvoxamine to communications about Merck’s drug molnupiravir. The evidence for molnupiravir is in many ways weaker than the evidence for fluvoxamine, but molnupiravir was produced by a major pharmaceutical company that can shepherd it through the process of becoming a recommended drug. On a call last week, Mills said, the FDA told him “they don’t know how to deal with submissions where there isn’t someone to be responsible for it.”
Mounjaro

Mounjaro is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 24, 2022 and November 30, 2022. The archive places it in contexts such as "Mounjaro sounds like the playful animal sidekick in a Disney movie"; "Eli Lilly’s coupon for Mounjaro was less restrictive at first"; "I am on Mounjaro, and have been for four months". It most often appears alongside Canada, Eli Lilly, FDA.

Article page
Mounjaro
Mention count
2
Issue count
2
First seen
November 24, 2022
Last seen
November 30, 2022
November 24, 2022 · Original source
The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Neuralink

Neuralink is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 04, 2022 and January 30, 2024. The archive places it in contexts such as "Imagine Elon Musk replaces his brain with a Neuralink computer"; "the first Neuralink has been implanted into a human being". It most often appears alongside Metaculus, 2013, 538.

Article page
Neuralink
Mention count
2
Issue count
2
First seen
April 04, 2022
Last seen
January 30, 2024
April 04, 2022 · Original source
Chess AI performance over time. Why does this matter? If there’s a slow takeoff (ie gradual exponential curve), it will become obvious that some kind of terrifying transformative AI revolution is happening, before the situation gets apocalyptic. There will be time to prepare, to test slightly-below-human AIs and see how they respond, to get governments and other stakeholders on board. We don’t have to get every single thing right ahead of time. On the other hand, because this is proceeding along the usual channels, it will be the usual variety of muddled and hard-to-control. With the exception of a few big actors like the US and Chinese government, and maybe the biggest corporations like Google, the outcome will be determined less by any one agent, and more by the usual multi-agent dynamics of political and economic competition. There will be lots of opportunities to affect things, but no real locus of control to do the affecting. If there’s a fast takeoff (ie sudden FOOM), there won’t be much warning. Conventional wisdom will still say that transformative AI is thirty years away. All the necessary pieces (ie AI alignment theory) will have to be ready ahead of time, prepared blindly without any experimental trial-and-error, to load into the AI as soon as it exists. On the plus side, a single actor (whoever has this first AI) will have complete control over the process. If this actor is smart (and presumably they’re a little smart, or they wouldn’t be the first team to invent transformative AI), they can do everything right without going through the usual government-lobbying channels. So the slower a takeoff you expect, the less you should be focusing on getting every technical detail right ahead of time, and the more you should be working on building the capacity to steer government and corporate policy to direct an incoming slew of new technologies. Yudkowsky Contra Christiano Eliezer counters that although progress may retroactively look gradual and continuous when you know what metric to graph it on, it doesn’t necessarily look that way in real life by the measures that real people care about. (one way to think of this: imagine that an AI’s effective IQ starts at 0.1 points, and triples every year, but that we can only measure this vaguely and indirectly. The year it goes from 5 to 15, you get a paper in a third-tier journal reporting that it seems to be improving on some benchmark. The year it goes from 66 to 200, you get a total transformation of everything in society. But later, once we identify the right metric, it was just the same rate of gradual progress the whole time. ) So Eliezer is much less impressed by the history of previous technologies than Paul is. He’s also skeptical of the “GDP will double in 4 years before it doubles in 1” claim, because of two contingent disagreements and two fundamental disagreements. The first contingent disagreement: government regulations make it hard to deploy imperfect things, and non-trivial to deploy things even after they’re perfect. Eliezer has non-jokingly said he thinks AI might destroy the world before the average person can buy a self-driving car. Why? Because the government has to approve self-driving cars (and can drag its feet on that), but the apocalypse can happen even without government approval. In Paul’s model, sometime long before superintelligence we should have AIs that can drive cars, and that increases GDP and contributes to a general sense that exciting things are going on. Eliezer says: fine, what if that’s true? Who cares if self-driving cars will be practical a few years before the world is destroyed? It’ll take longer than that to lobby the government to allow them on the road. The second contingent disagreement: superintelligent AIs can lie to us. Suppose you have an AI which wants to destroy humanity, whose IQ is doubling every six months. Right now it’s at IQ 200, and it suspects that it would take IQ 800 to build a human-destroying superweapon. Its best strategy is to lie low for a year. If it expects humans would turn it off if they knew how close it was to superweapons, it can pretend to be less intelligent than it really is. The period when AIs are holding back so we don’t discover their true power level looks like a period of lower-than-expected GDP growth - followed by a sudden FOOM once the AI gets its superweapon and doesn’t need to hold back. So even if Paul is conceptually right and fundamental progress proceeds along a nice smooth curve, it might not look to us like a nice smooth curve, because regulations and deceptive AIs could prevent mildly-transformative AI progress from showing up on graphs, but wouldn’t prevent the extreme kind of AI progress that leads to apocalypse. To an outside observer, it would just look like nothing much changed, nothing much changed, nothing much changed, and then suddenly, FOOM. But even aside from this, Eliezer doesn’t think Paul is conceptually right! He thinks that even on the fundamental level, AI progress is going to be discontinuous. It’s like a nuclear bomb. Either you don’t have a nuclear bomb yet, or you do have one and the world is forever transformed. There is a specific moment at which you go from “no nuke” to “nuke” without any kind of “slightly worse nuke” acting as a harbinger. He uses the example of chimps → humans. Evolution has spent hundreds of millions of years evolving brainier and brainier animals (not teleologically, of course, but in practice). For most of those hundreds of millions of years, that meant the animal could have slightly more instincts, or a better memory, or some other change that still stayed within the basic animal paradigm. At the chimp → human transition, we suddenly got tool use, language use, abstract thought, mathematics, swords, guns, nuclear bombs, spaceships, and a bunch of other stuff. The rhesus monkey → chimp transition and the chimp → human transition both involved the same ~quadrupling of neuron number, but the former was pretty boring and the latter unlocked enough new capabilities to easily conquer the world. The GPT-2 → GPT-3 transition involved centupling parameter count. Maybe we will keep centupling parameter count every few years, and most times it will be incremental improvement, and one time it will conquer the world. But even talking about centupling parameter points is giving Paul too much credit. Lots of past inventions didn’t come by quadrupling or centupling something, they came by discovering “the secret sauce”. The Wright brothers (he argues) didn’t make a plane with 4x the wingspan of the last plane that didn’t work, they invented the first plane that could fly at all. The Hiroshima bomb wasn’t some previous bomb but bigger, it was what happened after a lot of scientists spent a long time thinking about a fundamentally different paradigm of bomb-making and brought it to a point where it could work at all. The first transformative AI isn’t going to be GPT-3 with more parameters, it will be what happens after someone discovers how to make machines truly intelligent. (this is the same debate Eliezer had with Ajeya over the Biological Anchors post; have I mentioned that Ajeya and Paul are married?) Fine, Let’s Nitpick The Hell Out Of The Chimps Vs. Humans Example This is where the two of them end up, so let’s follow. Between chimps and humans, there were about seven million years of intermediate steps. These had some human capabilities, but not others. IE homo erectus probably had language, but not mathematics, and in terms of taking over the world it did make it to most of the Old World but was less dominant than moderns. But if we say evolutionary history started 500 million years ago (the Cambrian), and AI history started with the Dartmouth Conference in 1955, then the equivalent of 7 million years of evolutionary history is 1 year of AI history. In the very very unlikely and forced comparison where evolutionary history and AI history go at the same speed, there will be only about a year between chimp-level and human-level AIs. A chimp-level AI probably can’t double GDP, so this would count as a fast takeoff by Paul’s criterion. But even more than that, chimp → human feels like a discontinuity. It’s not just “animals kept getting smarter for hundreds of millions of years, and then ended up very smart indeed”. That happened for a while, and then all of sudden there was a near-instant phase transition into a totally different way of using intelligence with completely new abilities. If AI worked like this, we would have useful toys and interesting specialists for a few decades, until suddenly someone “got it right”, completed the package that was necessary for “true intelligence”, and then we would have a completely new category of thing. Paul admits this analogy is awkward for his position. He answers: Chimp evolution is not primarily selecting for making and using technology, for doing science, or for facilitating cultural accumulation. The task faced by a chimp is largely independent of the abilities that give humans such a huge fitness advantage. It’s not completely independent—the overlap is the only reason that evolution eventually produces humans—but it’s different enough that we should not be surprised if there are simple changes to chimps that would make them much better at designing technology or doing science or accumulating culture […] So I don’t think the example of evolution tells us much about whether the continuous change story applies to intelligence. This case is potentially missing the key element that drives the continuous change story—optimization for performance. Evolution changes continuously on the narrow metric it is optimizing, but can change extremely rapidly on other metrics. For human technology, features of the technology that aren’t being optimized change rapidly all the time. When humans build AI, they will be optimizing for usefulness, and so progress in usefulness is much more likely to be linear. That is, evolution wasn’t optimizing for tool use/language/intelligence, so we got an “overhang” where chimps could potentially have been very good at these, but evolution never bothered “closing the circuit” and turning those capabilities “on”. After a long time, evolution finally blundered into an area where marginal improvements in these capacities improved fitness, so evolution started improving them and it was easy. Imagine a company which, through some oversight, didn’t have a Sales department. They just sat around designing and manufacturing increasingly brilliant products, but not putting any effort into selling them. Then the CEO remembers they need a Sales department, starts one up, and the company goes from moving near zero units to moving millions of units overnight. It would look like the company had “suddenly” developed a “vast increase in capabilities”. But this is only possible when a CEO who is weirdly unconcerned about profit forgets to do obvious profit-increasing things for many years. This is Paul’s counterargument to the chimp analogy. Evolution isn’t directly concerned about various intellectual skills; it only wants them in the unusual cases where they’ll contribute to fitness on the margin. AI companies will be very concerned about various intellectual skills. If there’s a trivial change that can make their product 10x better, they’ll make it. So AI capabilities will grow in a “well-rounded” way, there won’t be any “overhangs”, and there won’t be any opportunities for a sudden overhang-solving phase transition with associated new-capability development like with chimps → humans. Eliezer answers: Chimps are nearly useless because they're not general, and doing anything on the scale of building a nuclear plant requires mastering so many different nonancestral domains that it's no wonder natural selection didn't happen to separately train any single creature across enough different domains that it had evolved to solve every kind of domain-specific problem involved in solving nuclear physics and chemistry and metallurgy and thermics in order to build the first nuclear plant in advance of any old nuclear plants existing. Humans are general enough that the same braintech selected just for chipping flint handaxes and making water-pouches and outwitting other humans, happened to be general enough that it could scale up to solving all the problems of building a nuclear plant - albeit with some added cognitive tech that didn't require new brainware, and so could happen incredibly fast relative to the generation times for evolutionarily optimized brainware. Now, since neither humans nor chimps were optimized to be "useful" (general), and humans just wandered into a sufficiently general part of the space that it cascaded up to wider generality, we should legit expect the curve of generality to look at least somewhat different if we're optimizing for that. Eg, right now people are trying to optimize for generality with AIs like Mu Zero and GPT-3. In both cases we have a weirdly shallow kind of generality. Neither is as smart or as deeply general as a chimp, but they are respectively better than chimps at a wide variety of Atari games, or a wide variety of problems that can be superposed onto generating typical human text. They are, in a sense, more general than a biological organism at a similar stage of cognitive evolution, with much less complex and architected brains, in virtue of having been trained, not just on wider datasets, but on bigger datasets using gradient-descent memorization of shallower patterns, so they can cover those wide domains while being stupider and lacking some deep aspects of architecture. It is not clear to me that we can go from observations like this, to conclude that there is a dominant mainline probability for how the future clearly ought to go and that this dominant mainline is, "Well, before you get human-level depth and generalization of general intelligence, you get something with 95% depth that covers 80% of the domains for 10% of the pragmatic impact". ...or whatever the concept is here, because this whole conversation is, on my own worldview, being conducted in a shallow way relative to the kind of analysis I did in Intelligence Explosion Microeconomics, where I was like, "here is the historical observation, here is what I think it tells us that puts a lower bound on this input-output curve". Here Eliezer sort of kind of grants Paul’s point that AIs will be optimized for generality in a way chimps aren’t, but points to his previous “Intelligence Explosion Microeconomics” essay to argue that we should expect a fast takeoff anyway. IEM has a lot of stuff in it, but one key point is that instead of using analogies to predict the course of future AI, we should open that black box and try to actually reason about how it will work, in which case we realize that recursive self-improvement common-sensically has to cause an intelligence explosion. I am sort of okay with this, but I feel like a commitment to avoiding analogies should involve not bringing up the chimp-human analogy further, which Eliezer continues to do, quite a lot. I do feel like Paul succeeded in convincing me that we shouldn’t place too much evidential weight on it. The Wimbledon Of Reference Class Tennis “Reference class tennis” is an old rationalist idiom for people throwing analogies back and forth. “AI will be slow, because it’s an economic transition like the Agricultural or Industrial Revolution, and those were slow!” “No, AI will be fast, because it’s an evolutionary step like chimps → humans, and that was fast!” “No, AI will be slow, because it’s an invention, like the computer, and computers were invented piecemeal and required decades of innovation to be useful.” “No, AI will be fast, because it’s an invention, like the nuclear bomb, and nuclear bombs went from impossible to city-killing in a single day.” “No, AI will be slow, because it will be surrounded by a shell-like metallic computer case, which makes it like a turtle, and turtles are slow.” “No, AI will be fast, because it’s dangerous and powerful, like a tiger, and tigers are fast!” And so on. Comparing things to other things is a time-tested way of speculating about them. But there are so many other things to compare to that you can get whatever result you want. This is the failure mode that the term “reference class tennis” was supposed to point to. Both participants in this debate are very smart and trying their hardest to avoid reference-class tennis, but neither entirely succeeds. Eliezer’s preferred classes are Bitcoin (“there wasn't a cryptocurrency developed a year before Bitcoin using 95% of the ideas which did 10% of the transaction volume”), nukes, humans/chimps, the Wright Brothers, AlphaGo (which really was a discontinuous improvement on previous Go engines), and AlphaFold (ditto for proteins). Paul’s preferred classes are the Agricultural and Industrial Revolutions, chess engines (which have gotten better along a gradual, well-behaved curve), all sorts of inventions like computers and ships (likewise), and world GDP. Eliezer already listed most of these in his Intelligence Explosion Microeconomics paper in 2013, and concluded that the space of possible analogies was contradictory enough that we needed to operate at a higher level. Maybe so, but when someone lobs a reference class tennis ball at you, it’s hard to resist the urge to hit it back. Recursive Self-Improvement This is where I think Eliezer most wants to take the discussion. The idea is: once AI is smarter than humans, it can do a superhuman job of developing new AI. In his Microeconomics paper, he writes about an argument he (semi-hypothetically) had with Ray Kurzweil about Moore’s Law. Kurzweil expected Moore’s Law to continue forever, even after the development of superintelligence. Eliezer objects: Suppose we were dealing with minds running a million times as fast as a human, at which rate they could do a year of internal thinking in thirty-one seconds, such that the total subjective time from the birth of Socrates to the death of Turing would pass in 20.9 hours. Do you still think the best estimate for how long it would take them to produce their next generation of computing hardware would be 1.5 orbits of the Earth around the Sun? That is: the fact that it took 1.5 years for transistor density to double isn’t a natural law. It’s pointing to a law that the amount of resources (most notably intelligence) that civilization focused on the transistor-densifying problem equalled the amount it takes to double it every 1.5 years. If some shock drastically changed available resources (by eg speeding up human minds a million times), this would change the resources involved, and the same laws would predict transistor speed doubling in some shorter amount of time (naively 0.000015 years, although realistically at that scale other inputs would dominate). So when Paul derives clean laws of economics showing that things move along slow growth curves, Eliezer asks: why do you think they would keep doing this when one of the discoveries they make along that curve might be “speeding up intelligence a million times”? (Eliezer actually thinks improvements in the quality of intelligence will dominate improvements in speed - AIs will mostly be smarter, not just faster - but speed is a useful example here and we’ll stick with it) Paul answers: Summary of my response: Before there is AI that is great at self-improvement there will be AI that is mediocre at self-improvement. Powerful AI can be used to develop better AI (amongst other things). This will lead to runaway growth. This on its own is not an argument for discontinuity: before we have AI that radically accelerates AI development, the slow takeoff argument suggests we will have AI that significantly accelerates AI development (and before that, slightly accelerates development). That is, an AI is just another, faster step in the hyperbolic growth we are currently experiencing, which corresponds to a further increase in rate but not a discontinuity (or even a discontinuity in rate). The most common argument for recursive self-improvement introducing a new discontinuity seems be: some systems “fizzle out” when they try to design a better AI, generating a few improvements before running out of steam, while others are able to autonomously generate more and more improvements. This is basically the same as the universality argument in a previous section. Eliezer: Oh, come on. That is straight-up not how simple continuous toy models of RSI work. Between a neutron multiplication factor of 0.999 and 1.001 there is a very huge gap in output behavior. Outside of toy models: Over the last 10,000 years we had humans going from mediocre at improving their mental systems to being (barely) able to throw together AI systems, but 10,000 years is the equivalent of an eyeblink in evolutionary time - outside the metaphor, this says, "A month before there is AI that is great at self-improvement, there will be AI that is mediocre at self-improvement." (Or possibly an hour before, if reality is again more extreme along the Eliezer-Hanson axis than Eliezer. But it makes little difference whether it's an hour or a month, given anything like current setups.) This is just pumping hard again on the intuition that says incremental design changes yield smooth output changes, which (the meta-level of the essay informs us wordlessly) is such a strong default that we are entitled to believe it if we can do a good job of weakening the evidence and arguments against it. And the argument is: Before there are systems great at self-improvement, there will be systems mediocre at self-improvement; implicitly: "before" implies "5 years before" not "5 days before"; implicitly: this will correspond to smooth changes in output between the two regimes even though that is not how continuous feedback loops work. I got a bit confused trying to understand the criticality metaphor here. There’s no equivalent of neutron decay, so any AI that can consistently improve its intelligence is “critical” in some sense. Imagine Elon Musk replaces his brain with a Neuralink computer which - aside from having read-write access - exactly matches his current brain in capabilities. Also he becomes immortal. He secludes himself from the world, studying AI and tinkering with his brain’s algorithms. Does he become a superintelligence? I think under the assumptions Paul and Eliezer are using, eventually maybe. After some amount of time he’ll come across a breakthrough he can use to increase his intelligence. Then, armed with that extra intelligence, he’ll be able to pursue more such breakthroughs. However intelligent the AI you’re scared of is, Musk will get there eventually. How long will it take? A good guess might be “years” - Musk starts out as an ordinary human, and ordinary humans are known to take years to make breakthroughs. Suppose it takes Musk one year to come up with a first breakthrough that raises his IQ 1 point. How long will his second breakthrough take? It might take longer, because he has picked the lowest-hanging fruit, and all the other possible breakthroughs are much harder. Or it might take shorter, because he’s slightly smarter than he was before, and maybe some extra intelligence goes a really long way in AI research. The concept of an intelligence explosion seems to assume the second effect dominates the first. This would match the observation that human researchers, who aren’t getting any smarter over time, continue making new discoveries. That suggests the range of possible discoveries at a given intelligence level is pretty vast. Some research finds that the usual pattern in science is constant rate of discovery from exponentially increasing number of researchers, suggesting strong low-hanging fruit effects, but these seem to be overwhelmed by other considerations in AI right now. I think Eliezer’s position on this subject is shaped by assumptions like: If you have an AI as intelligent as Elon Musk today, then tomorrow you can run it on more hardware with a bit of normal human algorithmic progress, and get one twice as intelligent. So even if it would take Elon years to make a breakthrough, long before those years are up you’ll have an AI that can make breakthroughs much faster.
January 30, 2024 · Original source
Both 15% and 32% are low numbers, but Israelis in the comments bring up that there aren’t scheduled elections in 2024. So if Bibi didn’t resign and his coalition partners didn’t desert him, he could potentially cling on. And nobody clings to power more ferociously than Benjamin Netanyahu. That recent spike comes from Musk’s claim three hours ago that the first Neuralink has been implanted into a human being.
That recent spike comes from Musk’s claim three hours ago that the first Neuralink has been implanted into a human being.
Omegaven

Omegaven is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 06, 2021 and August 08, 2021. The archive places it in contexts such as "a fish-oil-based infant nutritional fluid called Omegaven"; "Europe had a fish-oil based fluid, Omegaven"; "Fresenius, who held the rights to Omegaven". It most often appears alongside Dr. Gura, Europe, FDA.

Article page
Omegaven
Mention count
2
Issue count
2
First seen
August 06, 2021
Last seen
August 08, 2021
August 06, 2021 · Original source
In my recent post on the FDA, I mentioned a story about a fish-oil-based infant nutritional fluid called Omegaven. The FDA took too long to approve it, and lots of infants died.
After more research, I’ve concluded that the story I told is basically true, although I got a few details wrong. I want to go over it at more length here to set the record straight and see what we can learn from it. My main source will be Dr. Kathleen Gura, the pharmacist most responsible for getting Omegaven approved. She won an award for her work, she gave a very long acceptance speech describing her adventure, and the transcript of her speech is where I’m getting most of this information.
Omegaven is a fluid for parenteral nutrition. If your digestive tract doesn’t work (a problem frequently associated with newborn babies), then you risk starving to death. Doctors can avert this by pumping nutrients directly into your veins through an IV. This is notoriously hard, because food has lots of nutrients, and if you try to put together a complete replacement for food you will probably miss something. The US standard is a nutrient fluid called Intralipid, which uses soybean oil as its main fat. Because of the usual random cross-national differences in medicine, Europe used a formulation with fish oil as the main fat (though I’m not sure whether they used it along with soybean or on its own). In the early 2000s, nobody thought there was any interesting difference between these.
August 08, 2021 · Original source
That story would be wrong. In 2013, NBC ran an article called Drug Treatment Omegaven That Could Save Infant Lives Not Yet Approved By FDA. In 2014, libertarian blogs were using it as an example of excessive FDA delay - here’s one of them (search for “Bureaucratic Delay Endangers Lives”). Also in 2014, I personally learned about this for the first time, when writing my review of The Perfect Health Diet (I thought the book was generally bad, but it did alert me to this issue and the evidence supporting Omegaven). In 2016, my friend Eliezer Yudkowsky started writing a book about bureaucratic inefficiency that used the FDA failure to approve Omegaven as one of its central cases; in 2017, he published it as Inadequate Equilibria and I reviewed it here, including a mention of the Omegaven story. In January 2018, my friend Kelsey Piper also blogged about the FDA’s failure to approve Omegaven. Finally, in July 2018, the FDA finally approved the drug. I’ve been hearing about this story for so long that I thought I could recite it from memory (I was wrong, which is why I screwed up so many details in the original).
I think this history might be one of the reasons Drum and I interpret this story so differently. Drum hears about Omegaven, checks and sees that it’s FDA approved, and thinks “well, things worked out well in the end, what’s he complaining about?” I heard about it years ago, saw it wasn’t FDA approved, was able to confirm that it was revolutionary and life-saving, thought “well, I guess a lot of people are going to die from not being able to get this”, and read a gradual stream of articles over the next few years confirming that babies were still dying. Then, long afterwards, the FDA approved it. I guarantee you this is less fun and more enraging than hearing about it after the fact.
I got this from a book and haven’t been able to figure out exactly what it’s referring to - there doesn’t seem to be a corresponding entry in Dr. Gura’s notes. I suspect it’s true, since I find a lot of “compassionate use of Omegaven” studies from around this time, but I can’t find the actual FDA document involved. In any case, if true it slightly exonerates the FDA, so it’s probably not one of my points of contention with Drum.
Ozempic®

Ozempic® is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 24, 2022 and March 12, 2025. The archive places it in contexts such as "the brand names Ozempic® (for the injectable)"; "Semaglutide (Ozempic®, Wegovy®, Rybelsus®)". It most often appears alongside Eli Lilly, Eli Lilly, FDA.

Article page
Ozempic®
Mention count
2
Issue count
2
First seen
November 24, 2022
Last seen
March 12, 2025
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
March 12, 2025 · Original source
Semaglutide (Ozempic®, Wegovy®, Rybelsus®)
Others are turning amateur chemist. You can order GLP-1 peptides from China for cheap. Once you have the peptide, all you have to do is put it in the right amount of bacteriostatic water. In theory this is no harder than any other mix-powder-with-water task. But this time if you do anything wrong, or are insufficiently clean, you can give yourself a horrible infection, or inactivate the drug, or accidentally take 100x too much of the drug and end up with negative weight and float up into the sky and be lost forever. ACX cannot in good conscience recommend this cheap, common, and awesome solution.
PALM

PALM is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 18, 2022 and March 12, 2024. The archive places it in contexts such as "Second, PALM, a new and very impressive language AI:"; "he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa"; "twelve LLMs - including ... PaLM". It most often appears alongside Eliezer Yudkowsky, Metaculus, Asterisk.

Article page
PALM
Mention count
2
Issue count
2
First seen
April 18, 2022
Last seen
March 12, 2024
  • 22 April 18, 2022
  • 24 March 12, 2024
April 18, 2022 · Original source
Second, PALM, a new and very impressive language AI:
PALM explaining jokes (source) Third, Chinchilla, a paper and associated model suggesting that people have been training AIs inefficiently all this time, and that probably a small tweak to the process could produce better results with the same computational power.
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
Paxil

Paxil is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 31, 2021 and July 15, 2021. The archive places it in contexts such as "20 mg of paroxetine (Paxil)"; "The most effective dose of every SSRI would be: Paxil: 30 mg"; "their effort to market the antidepressant Paxil". It most often appears alongside SSRIs, 1902, 1903.

Article page
Paxil
Mention count
2
Issue count
2
First seen
March 31, 2021
Last seen
July 15, 2021
March 31, 2021 · Original source
16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
Prozac: 30 mg Paxil: 30 mg Zoloft: 75 mg Celexa: 30 mg Lexapro: 15 mg
July 15, 2021 · Original source
The frame story here is about a top anthropologist invited by GlaxoSmithKline to a lavish conference at a five-star resort in Japan. They asked him a bunch of questions about the cultural construction of mental illness. He pressed deeper and learned they were trying to “raise awareness of” depression in Japan as part of their effort to market the antidepressant Paxil there. This had, Watters thinks, much the same effect as “raising awareness of” anorexia in Hong Kong.
As part of GlaxoSmithKline’s marketing work, they replaced utsubyo with a new idea, kokoro no kaze, “cold of the soul”. This was supposed to mean that depression was a minor illness (like a cold), something everyone got occasionally (like a cold), and something that was purely biological and could/should be controlled with medication (like a cold). Japanese people were extremely excited about this and bought Paxil by the bushel, and now they use SSRIs at a rate close to Americans.
I was kind of unimpressed with this chapter. It seems pretty obvious that Japanese people got depressed before Paxil’s marketing campaign, including depressed to the point of suicide. GlaxoSmithKline comes off looking a bit manipulative, but it does kind of seem like the rush to get Paxil after their advertising campaign was less “sinister pharma company invents a new disease” and more “oh my god, there’s a name for this thing that I’m suffering from and maybe someone can help me!” There’s certainly a philosophical issue here - do you shrug off depression as just a part of life, or medicalize it? - but it’s not obvious that there’s anything different or uniquely Japanese about this question, or that Westerners made anything worse by exposing Japan to our solution.
Pfizer

Pfizer is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 04, 2022 and May 18, 2022. The archive places it in contexts such as "Pfizer’s vaccine is safe"; "gotten money from Pfizer". It most often appears alongside ADHD, AGI, America.

Article page
Pfizer
Mention count
2
Issue count
2
First seen
January 04, 2022
Last seen
May 18, 2022
January 04, 2022 · Original source
But apply it to COVID, and it’s even worse. Dr. Fauci and the CDC tell me every day that Pfizer’s vaccine is safe - but Male Scientist and NASA told their victims every day that Tech Company’s comet retrieval plan was safe. Sounds like we can’t trust scientific authorities when there might be a profit motive involved, better skip the jab! I hear ivermectin looks promising…
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Photoshop

Photoshop is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 30, 2020 and May 30, 2025. The archive places it in contexts such as "Download it and check on Paint or Photoshop"; "Learning Photoshop?". It most often appears alongside 3Blue1Brown, Aella, Alasdair MacIntyre.

Article page
Photoshop
Mention count
2
Issue count
2
First seen
August 30, 2020
Last seen
May 30, 2025
August 30, 2020 · Original source
The top and bottom chess sets in this picture are exactly the same color. Download it and check on Paint or Photoshop if you don't believe me. We use "as different as black and white" to mean obviously, undeniably different. But in fact a slightly different context can confuse our brains so completely that we mistake white for black and vice versa. I believe the same laws of thought apply in the frontal lobe as in the visual cortex. The same forces that transform gray chess sets to white or black, outside our conscious control or comprehension, influence how we think about policies, coalitions, and principles, making them appear self-evidently good or viciously evil. I think this is the century where we'll either learn to understand and deal with our cognitive biases, or else all kill each other.
May 30, 2025 · Original source
Consider, instead, just how irrelevant, useless, and impractical many of the things were that you threw yourself into when you were that age. Running a D&D campaign? Modding Half-Life? Learning Photoshop? Designing a fictional language? The real concerns of people run much deeper than what we’re likely to think of when we try to make something “relevant”.
Pokémon

Pokémon is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between July 14, 2023 and April 01, 2025. The archive places it in contexts such as "Pokémon takes the tool of “collections” and turns it into an international obsession"; "it can’t even beat Pokémon yet". It most often appears alongside England, Erik Hoel, Pokémon.

Article page
Pokémon
Mention count
2
Issue count
2
First seen
July 14, 2023
Last seen
April 01, 2025
July 14, 2023 · Original source
That is to say: these aren’t stages we move through, they’re Pokémon we collect. And the goal — of course! — is to collect ’em all.
Pokémon takes the tool of “collections” and turns it into an international obsession. I feel like the more people learn to use these tools, the more money they can make. We’re Egan-izing everything.
April 01, 2025 · Original source
This is what I fear most about AI, at least in the immediate future. Not some superintelligence that eats the world (it can’t even beat Pokémon yet, a game many of us conquered at ten). Rather, a less noticeable apocalypse. Culture following the same collapse as community on the back of a whirring compute surplus of imitative power provided by Silicon Valley. An oversupply that satiates us at a cultural level, until we become divorced from the semantic meaning and see only the cheap bones of its structure. Once exposed, it’s a thing you have no relation to, really. Just pixels. Just syllables. In some order, yes. But who cares?
Prazosin

Prazosin is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 22, 2021 and June 16, 2022. The archive places it in contexts such as "Prazosin for PTSD nightmares? Off-label and dirt-common"; "Prazosin is the standard anti-nightmare drug, and can be taken at doses from 1 - 12 mg". It most often appears alongside Scott, Amazon, aspirin.

Article page
Prazosin
Mention count
2
Issue count
2
First seen
December 22, 2021
Last seen
June 16, 2022
December 22, 2021 · Original source
Or maybe you’re afraid of lawsuits. If you get sued for malpractice, it’s nice to be able to tell the jury “it says this drug is okay for this condition right on the label”. But this doesn’t usually stop doctors from doing off-label prescriptions. Gabapentin is the 18th most-prescribed drug in the US, almost always for nerve pain or anxiety, but its label only officially endorses use for seizures or shingles. Beta-blockers for social anxiety? Off-label and dirt common. Prazosin for PTSD nightmares? Off-label and dirt-common. How do doctors sleep at night, knowing they’re constantly at risk of getting sued for off-label prescriptions? Probably using trazodone, the #2 most popular sleeping pill in the US, whose label says it should only be used for depression. No, seriously, it’s because most doctors don’t even know these indications are off-label, plus their medical school professors all did it too so it doesn’t feel transgressive.
June 16, 2022 · Original source
Summary: Nightmares happen when the process of dream generation is biased by ambient stress - or sometimes for other reasons. Anything that decreases stress, increases comfort while sleeping, and deepens sleep quality will also improve nightmares, including colder, darker rooms, less indigestion, and treating any comorbid psychiatric or medical conditions. If that doesn’t work, several kinds of therapy - including Image Rehearsal Therapy, Systematic Desensitization, and Lucid Dreaming - may be helpful. Prazosin is the standard anti-nightmare drug, and can be taken at doses from 1 - 12 mg, but watch out for side effects.
We’ll look at a few of these further: Desensitization and LDT, the two highest-performing therapies. IRT, the best-studied therapy. And prazosin, the highest-performing medication.
The standard of care is prazosin, an alpha-blocker. Here is a good review study.
quetiapine

quetiapine is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 25, 2021 and May 18, 2022. The archive places it in contexts such as "The usual procedure is to take an SSRI and use an antipsychotic, probably aripiprazole or quetiapine, on the side"; "Quetiapine, which makes people so sleepy ... plus has various bad long-term side effects". It most often appears alongside Carlat Report, SSRIs, 2002 meta-analysis by Cochrane Collaboration.

Article page
quetiapine
Mention count
2
Issue count
2
First seen
May 25, 2021
Last seen
May 18, 2022
May 25, 2021 · Original source
Antipsychotics are a class of drugs usually used against schizophrenia, but they also seem to have some role in depression. I hate using these because they have various concerning side effects if used for too long, but I will grudgingly include them at this part of the treatment algorithm. The usual procedure is to take an SSRI and use an antipsychotic, probably aripiprazole or quetiapine, on the side. Aripiprazole might make you restless, and quetiapine will make you sleep more and gain weight. Either one when used for too long increases your risk of metabolic problems (eg diabetes) and various terrible movement disorders (eg you can’t stop smacking your lips, and this problem never goes away). I don’t like these, but they sometimes work, and I can’t leave them out of the algorithm completely.
May 18, 2022 · Original source
Quetiapine, which makes people so sleepy that they forget to be anxious, plus has various bad long-term side effects.
Quorn Meatless Roast

Quorn Meatless Roast is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 30, 2023 and May 30, 2024. The archive places it in contexts such as "best fake turkey for Thanksgiving (it’s Quorn Meatless Roast)"; "where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast )"; "where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast)". It most often appears alongside Alcoholics Anonymous, EA, EA Forum.

Mention count
2
Issue count
2
First seen
November 30, 2023
Last seen
May 30, 2024
November 30, 2023 · Original source
And I’m a terrible vegetarian. If there’s meat in front of me, I’ll eat it. Luckily I’ve cultivated an EA friend group full of vegetarians and pescetarians, and they usually don’t place meat in front of me. My friends will cook me delicious Swedish meatballs made with Impossible Burger, or tell me where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast). And the Good Food Institute (an EA-supported charity) helps ensure I get ever tastier fake meat every year.
May 30, 2024 · Original source
And I’m a terrible vegetarian. If there’s meat in front of me, I’ll eat it. Luckily I’ve cultivated an EA friend group full of vegetarians and pescetarians, and they usually don’t place meat in front of me. My friends will cook me delicious Swedish meatballs made with Impossible Burger, or tell me where to find the best fake turkey for Thanksgiving (it’s Quorn Meatless Roast). And the Good Food Institute (an EA-supported charity) helps ensure I get ever tastier fake meat every year.
Rapamycin

Rapamycin is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 02, 2021 and June 18, 2025. The archive places it in contexts such as "A suitably foreboding one, even! Rapamycin gets its name from Rapa Nui"; "Mice on rapamycin live about 10% longer than usual"; "The drug that's furthest along is boosted rapamycin". It most often appears alongside Australia, US, 1DaySooner.

Article page
Rapamycin
Mention count
2
Issue count
2
First seen
December 02, 2021
Last seen
June 18, 2025
December 02, 2021 · Original source
The main thing I remember from my biochemistry classes is that mTOR is a big oval with the word “mTOR” on it. mTOR turns off in times of deprivation, so you can keep it off by depriving yourself. That’s why the gold standard of anti-aging interventions is calorie restriction: eat less food. This isn’t just the “stay thin if you don’t want to die of a heart attack” thing, this is where you eat an absurdly low amount of food, practically starving yourself, as a desperate strategy to turn off this one protein. This kind of extreme calorie restriction extends lifespan about 50% in lemurs, and would probably work for humans too. Sinclair brings up the story of a weird Venetian merchant who took some kind of vow of temperance and ate famously little each day: he lived to 100, which is pretty good for the 1500s. And:
Suppose you’re not a mouse, can’t get genetically engineered, and you have a normal aversion to diet and exercise. Is there a pill you can take? Yes! A suitably foreboding one, even! Rapamycin gets its name from Rapa Nui aka Easter Island, where it was discovered in a fungus living beneath one of the giant stone heads. It’s a strong inhibitor of mTOR (in fact, the “TOR” in mTOR’s name stands for “Target Of Rapamycin”). Mice on rapamycin live about 10% longer than usual. Can you take rapamycin? Probably a bad idea, it’s a potent immunosuppressant. Organ recipients take it sometime to quiet their immune system down to the point where it stops rejecting the transplant, but it’s not a lot of fun.
June 18, 2025 · Original source
We have two repurposed drugs that are clinical stage. The drug that's furthest along is boosted rapamycin, which we're using for chronic kidney disease in cats. We will have safety, stability, and pharmacokinetic data by July. Combined with the recent conditional approval of generic rapamycin for feline hypertrophic cardiomyopathy, this should put us in a good place to find a strategic partner.
Rybelsus®

Rybelsus® is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 24, 2022 and March 12, 2025. The archive places it in contexts such as "and Rybelsus® (for the pill)"; "Semaglutide (Ozempic®, Wegovy®, Rybelsus®)". It most often appears alongside Eli Lilly, Eli Lilly, FDA.

Article page
Rybelsus®
Mention count
2
Issue count
2
First seen
November 24, 2022
Last seen
March 12, 2025
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
March 12, 2025 · Original source
Semaglutide (Ozempic®, Wegovy®, Rybelsus®)
selegiline

selegiline is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 16, 2022 and May 15, 2024. The archive places it in contexts such as "none of the 17 patients they found were taking selegiline"; "was he taking the selegiline and adrafinil at the same time?"; "patient who took selegiline and lisdexamfetamine". It most often appears alongside effective altruist movement, @AutismCapital, @the_megabase.

Article page
selegiline
Mention count
2
Issue count
2
First seen
November 16, 2022
Last seen
May 15, 2024
November 16, 2022 · Original source
Milky Eggs reports a claim by an employee that Sam was on “a patch for designer stimulants that mainlined them into his blood to give him a constant buzz at all times”. This could be a hyperbolic description of Emsam, a patch form of the antidepressant/antiparkinsonian agent selegiline. The detectives at the @AutismCapital Twitter account found a photo of SBF, zoomed in on a scrap of paper on his desk, and recognized it as an Emsam wrapper.
Emsam is a brand of selegiline, a medication used since the 1960s to treat Parkinson’s disease. Selegiline is a MAOB inhibitor2. MAOB is an enzyme that breaks down dopamine3. If you inhibit it, you get more dopamine. So in a very broad sense, selegiline gives you more dopamine.4
Selegiline is an even less magical bullet than usual. People call it an antidepressant, anti-Parkinsonian, and stimulant, and all of those descriptions are accurate. It also does one unrelated thing: it disables a key digestive enzyme that prevents certain foods from killing you. For boring technical reasons, some pharma companies thought this might not happen if you delivered selegiline through a patch on the skin. For other boring technical reasons, the FDA disagreed and said people on the selegiline patch still shouldn’t eat those foods. The pharma companies decided to release the patch anyway, in case some people liked patches better than pills - and so Emsam was born.
May 15, 2024 · Original source
Pearce says: solving poverty and curing disease is very hard. And even if we did, it wouldn’t end human suffering. And even if it did, that wouldn’t end animal suffering. Suffering is a fundamentally biological process which requires a biological solution. Pearce found a biological solution to his own suffering; he alleviated his severe depression with the antidepressant selegiline. Selegiline isn’t for everybody; it can take the edge off negative experience, but it hardly makes you perfectly happy forever. To make people perfectly happy forever, we need to take this principle and build on it.
A partial near-term victory would look something like a universally available drug that could make people happy and pain-free with no side effects (so, for example, it wouldn’t turn you into a lotus-eater who sat blissed out on the couch your whole life, any more than seligiline did to Pearce himself). Total victory would require some kind of long-term change to the brain/body system that let it do all its normal work - growing, learning, working, changing - without pain, suffering, or any other negative emotion.
Shingles vaccine

Shingles vaccine is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 01, 2023 and October 30, 2025. The archive places it in contexts such as "Shingles vaccine probably reduces incidence of dementia"; "shingles vaccine significantly decreases dementia risk while in effect". It most often appears alongside Anthropic, Biden, Clinton.

Article page
Shingles vaccine
Mention count
2
Issue count
2
First seen
June 01, 2023
Last seen
October 30, 2025
June 01, 2023 · Original source
2: All the ancients, from Darius the Great to Augustus Caesar, agreed that the Nisean horse was the most majestic horse breed, the horse of kings. The Chinese fought a war (the War of Heavenly Horses) just to get access to a breeding stock. Then they sort of ambiguously went extinct during the Middle Ages. But here’s a modern Iranian horse enthusiast talking about which breeds might be its descendants. 3: Remember when the global community banned whaling, but some countries (eg Japan) continued doing it under the facade of “research”? With octopus factory farms under increasing scrutiny, UNAM university in Mexico is operating a “farm disguised as a research center”. 4: Genuinely new (to me) optical illusion: what is this guy is doing with his hands? Here’s a slow motion version that shows how it’s done. And some people in the replies were speculating this only works because of his dark skin, but here’s a white person doing the exact same thing (wait for it). 5: Shingles vaccine probably reduces incidence of dementia, suggesting that VZV (virus behind shingles and chickenpox) is a contributor. Further discussion here that I’m still trying to make sense of. 6: This deserves to go down in history alongside the wittiest Socratic comebacks in the Platonic dialogues: 7: Matt Lakeman: Notes On Nigeria. Great introduction to modern Nigerian history. Read it for the visceral understanding of the “resource curse” and why poor countries stay poor, but also: A savant is basically someone who has innate mental challenges but is extremely competent in a particular narrow domain. Some savants become obsessed with trains and become great engineers. Some become obsessed with computers and build software wonders. One of Abacha’s predecessors said of him: “He might not be bright upstairs, but he knows how to overthrow governments.” Kenyon elaborates: “It was as if Abacha was an idiot savant. Dull, even gormless, he filled his days with cowboy movies and sleeping off the previous night’s indulgences in alcohol and prostitutes. But he was possessed of a prodigious flair when it came to coups.” 8: Related to my previous subscribers-only post on the psychology of fantasy: Balioc’s Taxonomy Of What Magic Is Doing In Fantasy Books. See also Eliezer’s commentary. 9: New study on the timing of human mutations confirms Greg Cochran’s 2012 post about how after leaving Africa, modern humans were limited to “Arabia and surrounding regions” for ~30,000 - 50,000 years, racking up various new mutations and becoming adapted to life outside Africa (kabbalistically equivalent to the 40 years spent wandering in Sinai?). Most mutations in “fat storage, neural development, skin physiology, and cilia function”. 10: Iron Economist on Twitter: “Desalinization was one of the big technological success stories of the 2010s”. 11: Matt Bruenig argues against the Success Sequence, whose proponents (including Bryan Caplan) describe it as: 97% of Millennials who follow what has been called the “success sequence”—that is, who get at least a high school degree, work, and then marry before having any children, in that order—are not poor by the time they reach their prime young adult years (ages 28-34). Bruenig’s argument is mostly a lot of annoying “well maybe it’s just your cultural bias that makes you care about this”, but in the middle of this it mentions some genuinely strong points, especially that the research doesn’t measure “sequence”, but rather “current status”. So if you graduated, got a job, got married, and had children, but then lost your job, your would be counted as “not following the sequence” (same if you get divorced). Also, disabled and old people and their caretakers are excluded from the analysis, which in one sense is fair (your conclusion can be “abled young adults can avoid poverty through this method”) but in another sense risks reducing all of this to the more trivial-seeming statement “if you’re young, healthy, abled, married, don’t have to support anyone else, and have a full-time job, you’re probably not poor”. But the authors (channeled by Caplan) disagree: Some critics of the success sequence have argued that marriage does not matter once education and work status are controlled. The regression results indicate that after controlling for a range of background factors, the order of marriage and parenthood in Millennials’ lives is significantly associated with their financial well-being in the prime of young adulthood. Simply put, compared with the path of having a baby first, marrying before children more than doubles young adults’ odds of being in the middle or top income. Meanwhile, putting marriage first reduces the odds of young adults being in poverty by 60% (vs. having a baby first). The main thing I would want to look at here is how much of this is causal vs. just class selection: upper-class people are more likely to marry, less likely to divorce, and more likely to wait before having children. Has anyone followed some pre-selected group of equal class people (eg the population of some low-income school district) and seen how their own success varies with sequence compliance? 12: I’ve previously linked claims that vat-grown meat, freed from the tyranny of having to grow inside animals, will include tiger steaks, lion burgers, and the like. Once again global capitalism outpaces my wildest fantasies and offers burgers with woolly mammoth protein (so far just the myoglobin, not the meat). 13: The people who believed there was lots of gender bias in STEM academia, and the people who believed there wasn’t finally did an adversarial collaboration (a study co-conducted by two groups of scientists with conflicting theories, keeping each other honest). The results: Contrary to the omnipresent claims of sexism in these domains appearing in top journals and the media, our findings show that tenure-track women are at parity with tenure-track men in three domains (grant funding, journal acceptances, and recommendation letters) and are advantaged over men in a fourth domain (hiring). For teaching ratings and salaries, we found evidence of bias against women; although gender gaps in salary were much smaller than often claimed, they were nevertheless concerning. For ten years lots of important people told us again and again that discrimination against women in STEM was a massive problem. People who questioned its extent were accused of misogyny and sometimes fired, I got harassed and insulted for pointing out reasons the standard arguments didn’t seem to hold true. Millions of dollars were spent investigating and responding to the problem. And now I expect this pretty strong evidence that women were actually advantaged in hiring and had parity in most other things (the salary is probably just the usual negotiation issue) to produce no publicity, no apologies, and no soul-searching from the people leading the current round of anti-academia and anti-STEM inquisitions. Sorry, yes I am bitter, it just bothers me how much the people claiming that it’s urgently important that nobody is ever allowed to suggest they are wrong have a consistent track record of being totally and inexcusably wrong. 14: In my response to Sam Kriss, I speculated on what would happen if someone rewrote the MCU to sound like ancient myths. Thanks to the many people who reminded me of Star Wars as Icelandic saga and Star Wars as Irish epic. And Sam has a response . 15: @AISafetyMemes on Twitter is exactly what you’d expect from the name. I especially like the fire dogs: More here: 16: More AI links from this month: Can’t even list all the new people who have come out as AI x-risk believers, but you can just read the CAIS statement. The top signatures are Geoff Hinton, Yoshua Bengio, Demis Hassabis, Sam Altman, and Dario Amodei; aside from the usual suspects, they also have Bruce Schneier (computer security expert) , Dawn Song (computer scientist and security expert), Andy Clark (professor of cognitive philosophy, wrote Surfing Uncertainty), Eliezer Yudkowsky (he didn't sign the last one because he disagreed with specifics, but he's here), and a former US Assistant Secretary of Defense for Nuclear, Chemical, and Biological Defense.
October 30, 2025 · Original source
43: Related: most people have the varicella zoster herpesvirus (aka chickenpox virus) latent in their bodies. Occasionally it reactivates in old people with bad immune systems and causes a rash called shingles, so old people are recommended to get the shingles vaccine. A new study shows that herpesvirus reactivation may be involved in dementia, and that the shingles vaccine significantly decreases dementia risk while in effect (~5 years). Celebrity epidemiologist Eric Feigl-Ding suggests that young people try getting the shingles vaccine for dementia prevention even if they don’t need it for shingles, but the exact pathway (and whether it helps preemptively) is not clear, and I think this is still a minority opinion. Here is ChatGPT’s assessment.
Somryst

Somryst is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 12, 2021 and May 14, 2021. The archive places it in contexts such as "Make sure that every use of Somryst is associated with a doctor’s prescription"; "the company behind Somryst. If you let a for-profit company charge $899 for an app"; "make an affordable and accessible version of Somryst". It most often appears alongside FDA, Pear Therapeutics, US.

Article page
Somryst
Mention count
2
Issue count
2
First seen
May 12, 2021
Last seen
May 14, 2021
May 12, 2021 · Original source
Until now! Late last year, Pear Therapeutics released a CBT-i app (formerly “SHUT-i”, now “Somryst”) which holds the patient’s hand through the complicated CBT-i process. Studies show it works as well as a real therapist, which is very well indeed. There’s only one catch: you need a doctor’s prescription.
Wait, you can prescription-gate an app? Yes! Although you can download Somryst off your normal App Store, it won’t work until a doctor writes you a prescription to “activate” it. Until then, it just shows you ads for how great CBT-i would be if you could get it.
And it’s not just Somryst. I know of at least three other prescription apps. reSET and reSET-O are 12-week courses to help addiction and opioid addiction, respectively. EndeavourRx is a video game which is supposed to help manage ADHD in kids. I guarantee you there are a lot more of these in the pipeline.
May 14, 2021 · Original source
There are a lot of studies here, but I'm going to choose two kind of random ones. Taylor et al show that in-person cognitive behavioral therapy for insomnia has an effect size of 0.98, and the same therapy delivered over the Internet has an effect size of 0.51 (both numbers significantly different from control, not significantly different from each other). Somryst itself has significantly outperformed placebo in several studies. A meta-analysis finds that "Low to moderate grade evidence suggests CBT-I has superior effectiveness to benzodiazepine and non-benzodiazepine drugs in the long term, while very low grade evidence suggests benzodiazepines are more effective in the short term".
It looks like Somryst was simultaneously assessed through the 510k pathway and some kind of lighter touch test regulatory procedure for apps from trusted vendors. Looks like they're currently running apps through both processes to compare the results (and presumably see if the new process misses anything disastrous).
https://peartherapeutics.com/pear-therapeutics-obtains-fda-authorization-for-somryst-a-prescription-digital-therapeutic-for-the-treatment-of-adults-with-chronic-insomnia/
Sora

Sora is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 20, 2024 and October 30, 2025. The archive places it in contexts such as "OpenAI’s Sora text-to-video engine"; "If the Sora app has your face". It most often appears alongside Biden, COVID, OpenAI.

Article page
Sora
Mention count
2
Issue count
2
First seen
February 20, 2024
Last seen
October 30, 2025
February 20, 2024 · Original source
The big AI excitement this month was around OpenAI’s Sora text-to-video engine. Here’s what forecasters thought would be true of it by end 2025:
The big AI excitement this month was around OpenAI’s Sora text-to-video engine. Here’s what forecasters thought would be true of it by end 2025: You can see many more (including “It was jailbroken and used to make porn: 54%”) at the link.
You can see many more (including “It was jailbroken and used to make porn: 54%”) at the link.
October 30, 2025 · Original source
2: Prediction by Jurgen Gravestein: “I don’t think people realize what kind of ads are coming. If the Sora app has your face, you will in the near future see ads of yourself wearing clothes of a certain brand.”
Spartacus.app

Spartacus.app is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between September 23, 2024 and April 06, 2026. The archive places it in contexts such as "assurance contract platform to solve coordination problems called Spartacus.app"; "Spartacus.app is urgently seeking a freelance TypeScript/Next.js/Supabase developer". It most often appears alongside ACX, Anthropic, Astralcodexten Com.

Article page
Spartacus.app
Mention count
2
Issue count
2
First seen
September 23, 2024
Last seen
April 06, 2026
September 23, 2024 · Original source
1: ACX Grantees Jordan Braunstein and TetraSpace are working on an assurance contract platform to solve coordination problems called Spartacus.app. They’ve asked me to announce:
That they’re looking for beta testers to provide feedback on some new features in development. You can join the current beta cohort here, or by going to their website and using the code 259100
That they have an open EA community choice fundraiser at Manifund to help extend their runway and pursue EA-aligned use cases. You can reach out to jordan@spartacus.app with any questions.
April 06, 2026 · Original source
6: ACX grantee Spartacus asks me to advertise that they’re looking for a developer:
Spartacus.app is urgently seeking a freelance TypeScript/Next.js/Supabase developer. Spartacus is a live platform for conditional-commitment collective action, with successful pilots involving unions and AI safety organizations. Our primary developer departed unexpectedly, and we need someone to pick up active development immediately. This is a remote, project-based contract with negotiable compensation plus possible revenue sharing (tools reimbursed). Strong TypeScript/Next.js/Supabase skills, along with fluency in AI coding tools (Claude Code, Cursor), are required. Detailed role requirements here. Reach out to jordan@spartacus.app
Stable Diffusion

Stable Diffusion is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 30, 2023 and July 18, 2025. The archive places it in contexts such as "to get my desires across to this stable diffusion model"; "not the kind generated by stable diffusion". It most often appears alongside ACX, Scott, 16th century Spain.

Article page
Stable Diffusion
Mention count
2
Issue count
2
First seen
August 30, 2023
Last seen
July 18, 2025
August 30, 2023 · Original source
But the rest was really good — consistent characters and outfits, just missing the bottom. After a few hours of experimentation and re-rolling we could generally end up with the ideal full-body image, including feet. I developed a whole toolbox of tricks, from changing the aspect ratio to be really tall to blending in an example pose as a second image. One of the tricks to get this was to get really specific about the feet. What kind of shoes and socks? Mentioning feet a few times with emphasis. Things like that. My language was one that I imagine a foot-fetishist’s google search history. "Tall woman with feet showing, high heels, extra feet please with an order of foot." Or extreme detail like "orange nikes with shoelaces and socks and shadows under the shoes" That would generally convince the AI that the feet should also be shown. Not all the time, but some combination helped. I dreamt of feet, and kept trying to come up with more synonyms to get my desires across to this stable diffusion model.
July 18, 2025 · Original source
To the extent that I’ve been able to create or replicate some of these patterns, the process reminds me of procedurally generated art — not the kind generated by stable diffusion, but the old school kind, generated by explicitly specified algorithms, autonomous systems, or the manipulation of randomness. As I understand it, there is often an experimental component: the artist begins with a vision, cooks up procedures, sees what comes out, then iterates, refining the method or sampling new random outputs with different seeds.
Starbucks

Starbucks is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 16, 2021 and May 10, 2023. The archive places it in contexts such as ""a Starbucks, a hotdog stand, are all improvements.""; "You can be a barista at Starbucks". It most often appears alongside Bay Area, California, China.

Article page
Starbucks
Mention count
2
Issue count
2
First seen
April 16, 2021
Last seen
May 10, 2023
April 16, 2021 · Original source
Will solve all our problems once and for all Why the Remedy is Just George asks, "what constitutes the rightful basis of property?" What gives you the right to say "this is mine?" George asserts as self-evident the principle that a person is entitled to the fruits of their labor. What you make on your own time with your own resources, is yours to do with as you please – use it, give it away, trade it, destroy it. You don't harm anyone else doing so. It follows that neither I nor anyone else am entitled to the product of your labor. If we're both independent hunter-gatherers, and you pick some berries from a bush, I don't have any fundamental right to demand them from you. If you improve land in some way, you're entitled to own and use that, of course. That's the product of your labor. But to claim exclusive and permanent ownership of the land itself – from which all wealth springs and without which labor is impossible – is to demand the product of other's labor. So to invoke the sanctity of private property to defend private land ownership is self-refuting. But what about the right of "I was here first?" Well, George points out that in most cases someone was there before you were, too (and often they were removed by force). Just because you arrived one second, one minute, one year, or one decade before someone else doesn't give you some fundamental right to exclude others from access to nature's free gifts. (Note: this doesn't give people the right to just come in your house and rifle through your underwear drawer at any time of day, we'll get to that). And what about native populations? Isn't this just an excuse for colonialists to come in and steal their land by denying their claim of being on the land first? By George, no – this is a good time to point out that many Native Americans already had a roughly Georgist understanding of land – treating it as common property, and it was precisely the colonialists' conception of land as private property that was the mechanism by which the indigenous population was expelled and their lands seized. The English first practiced this on their own people – once upon a time wide swaths of land in England were held in common until the government privatized those lands and gave them out to well-connected gentry in a process called Enclosure. If you've ever heard of the Luddites, you should know they weren't merely rebelling against the march of technology, they were also fighting against the forcible seizure of their lands by industrialists, who far from being salt-of-the-earth free-enterprise entrepreneurs, were in actual fact crony capitalists stealing the people's land with the aid of anti-free-market subsidies and armed thugs, all supported by Big Government™. As a practical matter though, if you want to impose a Georgist policy, that only applies to territory your state has authority over. Indian reservations in the United States are supposed to be sovereign enclaves with their own jurisdiction. Native Americans should decide for themselves whether they want to adopt any particular policy. The other reason the remedy is just, is that private ownership of land leads to serfdom. The essence of slavery is that it takes from the laborer all he produces save enough to support an animal existence, and to this minimum the wages of free labor, under existing conditions, unmistakably tend. George points out that even though Slavery was abolished, the Southern landowners just changed the brand name to "sharecropping" and were able to continue to extract tremendous wealth from "free" Black Americans in the form of rent. Okay, but excluding evil Southern plantation owners, don't landlords deserve compensation for their work? What about Ms. Nguyen, the nice lady who manages your apartment block and went the extra mile for you when your A/C went out last summer? I like Ms. Nguyen too, but let's contrast her with Mr. Slumlord, who owns the apartment block next door that's superficially identical, but who won't help you when your A/C goes out in the middle of summer. Ms. Nguyen charges higher "rent" for her much better maintained units because part of that "rent" is actually her justly compensated wages for her labor in managing them, as well as interest from returns on the capital she's invested in their ongoing improvement and maintenance. She also collects a good bit of true Georgian rent because she is, after all, a landlord. Mr. Slumlord puts in as little work as he can get away with and invests as little capital into maintenance as will keep the state off his back. His return is almost entirely rent. And the only reason he can charge rent in the first place is because of the valuable location – value the community produced, not him. And that's the real injustice of land rent – the community produces the value, but the landlord charges rent to access it. Practical Application of the Remedy Okay, land as common property, rent must die, I'm sold. How do we actually do it? George proposes a land value tax, or LVT. Note I didn't say property tax. Property tax is a tax on the value of a piece of land and it's improvements. So if you're a homeowner, when you pay property tax, you pay tax for both the value of your house and the lot it's sitting on. With land value tax you only pay tax on the "ground rent", which is the value of your land, but not the improvements. What's an improvement? By George, a little green house is an improvement. A fancy red hotel is an improvement. A garage, a sidewalk, a public park, a Starbucks, a hotdog stand, are all improvements. Installing a bunch of dikes in the Netherlands and dumping landfill into the seabed to turn wet land into dry is an improvement. All improvements come from labor, and optionally capital, and so its fair for those factors to take their return. If I "rent" you my hotdog stand (but not the lot it sits on) my return would be classified as interest in George's framework because the hotdog stand isn't land, it's capital – the stored-up fruits of my labor that I'm using to get more wealth. (Modified from source, CC BY 2.0, author: Philip Taylor) The problem with our current system is that when anyone in the community builds improvements, it makes adjoining land more valuable, and then those adjoining landlords jack up the rent. This makes things worse for everybody but the landlords. George's insight is that extra value from my improvement "spills over" from my land and is soaked up by the ground rent of your land. So under a land value tax, we can correct for the perverse economic incentives, distortions, and oppressions that come from land rent, without having to actually take your land from you. We may safely leave them the shell, if we take the kernel. It is not necessary to confiscate land — only to confiscate rent. You also are 100% the owner of the improvements on your land, which won't be taxed. This is why Georgism doesn't mean people have the right to barge into your house in the middle of the night even though land is "held in common." Your house is still private property, but the value of the land it sits on is common property. What if I plant some nice trees, and invest in some landscaping to stop erosion? Where's the line between "improvements" and "ground rent?" In most cases it's pretty straightforward to separately assess the value of a plot from the value of what sits on it (modern property tax assessors do this already), but George grants that in some edge cases with the passage of time at least some improvements will be subsumed into the land value and that's okay: But it will be said: There are improvements which in time become indistinguishable from the land itself! Very well; then the title to the improvements become blended with the title to the land; the individual right is lost in the common right. It is the greater that swallows up the less, not the less that swallows up the greater. Okay, ground rent bad. How much should we tax it? By George, One Hundred Percent. Take the rent the tenant has to pay each month, calculate the portion attributable to the value of the unimproved land itself, and send it to the taxing agency. Effects of the Remedy Wow! 100% tax rate on ground rent! Can we really do that? In practice Georgists often talk about rates closer to 85+% given real-world limitations in assessment, but the point is to hit it as hard as you possibly can. Get close enough and you still have good effects. Won't land taxes jack up land prices? No, actually - in fact it will do the opposite, because such a tax is laser-calibrated to eliminate speculation, which makes up the bulk of inflated land values, and thus rent. Tax land for the full ground rent and you make real estate more affordable, not less. Won't it enable an all-powerful centralized nanny state? Quite the opposite – land value assessment is a fundamentally bottom-up, localized task, so it naturally empowers local municipalities at the expense of distant central authorities. Also, income taxes, wealth taxes, investment taxes, etc, require an ever-vigilant centralized bureaucracy peeking into every aspect of an individual's life to catch tax evaders, who have every incentive to hide their assets or even just flee. Perversely, the IRS currently audits the poor at the same rate as the top 1%, even though higher earners are responsible for withholding the vast majority of tax money in fraud. Land can't move or hide, and nowadays we have tools like GIS to make it even easier to assess. Under land value tax, nobody needs to pry into your personal life or impose burdensome accounting rules on your small business that actually entrench the power of giant corporations (who have entire departments devoted to serving up the Double Irish with a Dutch Sandwich). A Brief Interlude From the Future Today land value tax is widely considered to be the only tax that doesn't suffer from Deadweight Loss. Deadweight Loss is the lost economic activity or value caused by some policy. It's often summarized by the phrase "If you want less of something, tax it." Look at this chart, for example: (source, CC BY-SA 2.5, author: SilverStar) The place where the demand curve (red) and supply curve (blue) meet is the equilibrium point that the market naturally tends towards. But if we impose a price control lower than what the market will bear, the yellow area of the curve shows economic activity that can't happen. If you put price controls on gasoline, for instance, you'll get shortages because there's more demand than supply, and supply can't profitably rise to meet the extra bit of demand that's willing to pay a little more. But here's how things look with a land value tax, notice that the supply curve is vertical – that's weird, what does that mean? (source, CC BY-SA 3.0, author: Explodicle) A vertical supply curve means no matter what the price of land is, the same amount will always be supplied. This is because you can't make land – the supply is effectively fixed. Remember, the Netherlands doesn't count because the sea bed is land, and filling it in is just an improvement to land that already existed. And even if we granted "The Netherlands occasionally makes land" for the sake of argument, the amount of land "created" in this way is pretty darn negligible in the grand scheme of the economy, and almost exclusively the domain of governments or state-owned actors. The supply of land being fixed has some really interesting properties. By contrast, consider oil, the supply of which is not fixed. If we tax oil, some of the more marginal wells will be too expensive to operate and make a profit, so producers shut those down and the supply of oil decreases. Deadweight loss comes from a producer's ability to change the amount of product they supply in response to price signals. You'll notice the above graph of land tax has no deadweight loss at all! Since nobody produces land, it's the one thing you can tax without getting less of it. This drives out speculators entirely. Speculators can no longer distort rents by bidding up the price of land and holding it out of use, and can no longer compete with those who actually intend to use the land. This restores the proper balance of land, labor, and capital. Now if you work harder, or invest more capital, you can actually expect to see an increasing return without it all being gobbled up by ever-increasing rent. If you think about it this way, land value tax has negative deadweight loss, because it eliminates the speculative distortion that is the unearned privilege of landownership. Okay, but won't the landlords just pass the land tax on to their tenants? By George, no. Rent is a price, and price is governed by supply and demand. Supply of land is fixed, so land value tax has no effect on supply. What about demand? Except in cases where it causes the economy to boom (a good thing), land value tax won't increase land value – what it always does, however, is reduce the demand for land by speculators. If it costs nothing to hold on to land, of course I'm going to want to grab some and HODL. If the rent I could hope to gain is taxed away, I won't bother. Consider the case of oil again, where a tax reduces the supply. Reduced supply, given unchanged demand, causes a rise in price. And you'll find the increase in price tracks very closely with the amount of tax. Land value tax is just about the only kind of tax that can't be passed off to someone else. For more on deadweight loss and the land value tax, see Welfare Economics of the Land Value Tax by BlueRepublik. So does this mean there can never be profitable landlords ever again? Of course not – they just have to earn their living honestly like everyone else. Remember, we don't tax the improvements, just the "ground rent." So Ms. Nguyen still gets paid for all her honest work and judicious investments, but Mr. Slumlord doesn't make a dime until he gets off his lazy butt and does something productive. This is really important, because aside from speculation, the principal cause of land value increase is the productivity of your neighbors. An empty lot in the middle of nowhere is worthless, but an otherwise identical empty lot in the middle of New York city is priceless. As they say in real estate - "location, location, location." The reason location is valuable is because of the activity and contributions of the community, and yet the landlord claims the right to seize it all as rent. Modern economists have some interesting things to say about George's ideas, too. In 1977 Joseph Stiglitz demonstrated that land rents have a tendency to almost perfectly equal the value of investment in public goods. He called this the Henry George Theorem. Milton Friedman famously called land value tax the "Least Worst" tax. But one of my all-time favorite endorsements will always be that one time the economist Ramin Shokrizade unwittingly re-derived land value tax from first principles to (successfully!) fix recessions in EVE Online. Okay, so we tax all the ground rent. It will remove the speculative component of the rent (because there will no longer be any incentive to jack the prices up artificially), but it won't drive the price down to zero. That's because 100% LVT is only achievable on a frictionless plane populated by spherical cows; here in the real world you'll be left with a small sliver of land value. And of course regardless of the LVT rate, houses and buildings will still have a price. And that's fine. Land in Times Square will still be a lot more valuable than land in Podunk, Saskatchewan, but both will approach the same price as the LVT rate gets closer to 100%. This encourages people to actually make use of valuable land rather than holding it out of use, blighting the urban core and forcing development to sprawl out for miles in every direction, leading to worse transportation and more pollution. But... doesn't this mean that if people aren't putting land to productive use, they'll eventually be pressured to sell it off to someone who will? George sees this as a good thing. Without land value tax you get situations where somebody can anticipate that an empty lot will become valuable in the future, buy it, HODL forever, lobby against future development that would depress their property values, and now you have the Bay Area's housing crisis. Or buy an apartment block, do the absolute minimum the tenants will tolerate without killing you, constantly jack up the rent as the city grows, and you get slums. As BlueRepublik observes in No, Georgism is Still Sane: If you look at the commercial blight in New York City (http://www.vacantnewyork.com/) 90%+ is from landlords refusing to lease out to small businesses, waiting for a larger bank or big business to pay a higher rent bill. This causes property values of nearby businesses to drop, equity value to drop, and businesses to move out from the city center, increasing urban sprawl and urban blight. It’s a massive drain on personal wealth, and is very highly linked with poverty and higher crime rates. It’s also not a great model for having a stable social fabric. In a fit of performance art, a Georgist by the name of Fay Lewis once famously bought an empty lot and stuck a big sign on it to demonstrate the principle in action: Okay, but isn't building too much stuff bad for the environment? Won't this encourage over-development? By George, no. What's bad for the environment is sprawl, which the current system encourages and which the land tax would directly attack. If you want dense, walkable cities that don't depend on cars to get around, you should eliminate land speculation. A stronger objection to land value tax is when it's not some shifty speculator or a genocidal English landlord who suffers the brunt of it, but, say, this guy: The premise of Pixar's movie Up is that Carl Fredricksen, a lovably grumpy pensioner, is the last holdout standing in the way of developers bulldozing the rest of his neighborhood in the name of Progress™. He refuses to sell because he can't bear to part with the house which for him is tied up with all the cherished memories of his departed wife. This isn't just sentimental fiction, this is something that really does happen. Isn't Georgism just going to price the poor Carl Fredricksens out of their homes so that someone with a more """productive""" use can have it instead? There's several good response to this. For starters, if you're worried about kindly old people losing their homes, that's a thing that's happening already, and most of the time it's because The Rent Is Too Damn High, and our existing system is net worse on this score. We are currently facing an unprecedented crisis of evictions in tandem with the COVID pandemic, and it's not like things were peachy before. And even though homelessness seems to be declining in the US overall, it's getting worse in the most prosperous cities, exactly as George predicted. Okay, maybe it's better for renters, but what about people who own their homes, like Carl? Isn't it unfair to stick them with land taxes that might kick them out? What if they're retired? Remember, let's not confuse land tax with land confiscation, Here's George (emphases mine): I do not propose either to purchase or to confiscate private property in land. The first would be unjust; the second, needless. Let the individuals who now hold it still retain, if they want to, possession of what they are pleased to call their land. Let them continue to call it their land. let them buy and sell, and bequeath and devise it. We may safely leave them the shell, if we take the kernel. It is not necessary to confiscate land; it is only necessary to confiscate rent. Okay, but you have to admit that even if the state isn't confiscating everybody's land, if you can't pay your land taxes you have no choice but to sell your land, right? Isn't this morally unjust to the Carl Fredricksens of the world? First, it's not a given that Mr. Fredricksen will be worse off on net: he already pays income and sales taxes, capital gains on any investments, as well as property tax which taxes both land value and the value of his house. As speculators leave the real estate market the land tax that replaces his property tax drop will drop, and his house is an improvement that goes entirely untaxed. Also, if the speculators holding onto all the most valuable real estate in the downtown districts are forced to give it up, there won't be as much competition for land and so there's a good chance developers won't be interested in trying to buy up land in a bedroom community in the first place. BlueRepublik further points out that LVT can be used to fund a Universal Basic Income, which should soften the blow considerably: Keep in mind also that the Georgist Land Value Tax is pair with a "Citizen's Dividend" or what we see as UBI, so that it's not the government claiming land rent, rather the land rent is taxed and split up equally for all men. But as a matter of political practicality, in the rare event that after all that Mr. Fredricksen still somehow finds himself in the hole after LVT is applied, Nate Blair suggests a deferment option to grandfather the Carls of the world through the transition: The LVT gets assessed annually for everyone, but owner occupiers (businesses and homeowners) can apply to defer the sum of those payments until they sell or transfer the land. Government can charge a nominal interest. A final point of modern application of land value taxes is to level the playing field between different areas by eliminating "cost of living" discrepancies that arise entirely from speculative rent. This is pretty relevant given the "location pay" debate going on in Silicon Valley right now in response to increased remote work as a direct consequence of the COVID pandemic. Back to George. Great, we've taxed ground rent at 100% and eliminated speculation and all other manner of social ills. Now what do we do with the money? Lots of things! For one, you can get rid of some other taxes. Back in George's day it was even argued that a 100% land value tax on ground rents should be the only tax – the "Single Tax," replacing all other tariffs, duties, and other taxes (keep in mind this was in the late 1800's and Federal income tax wasn't introduced until the 16th amendment in 1913). Remember, all these other taxes have deadweight loss. Income tax is a tax on labor, and so taxing it means we really do get less productive labor. The portion of property tax that targets improvements punishes you for investing in improvements, and sales tax is just straight up regressive, hitting the poor harder than the rich. There's some argument today about whether the "Single Tax" would be enough to fund the modern US budget, with some Georgists saying it would be sufficient and others saying we would still need some other taxes but could at least significantly offset what we already have. But by George, another thing we could do is just give all the money back to the people, as BlueRepublik mentioned above. This could be used as a straightforward Universal Basic Income – what George calls a Citizen's Dividend, or what Andrew Yang calls the Freedom Dividend. It could also be used for the funding of public goods. George doesn't see this as an act of charity on the state's behalf – the value of the land has its origin in the productive labors of the entire community, so it's a simple act of justice to give the returns to those who actually produced the value, which is society at large. Another effect George asserts is that once land is no longer monopolized, labor is no longer forced into one-sided competition, so wages start to go up. Even better, laborers now have far more opportunity to go into business for themselves, which spurs innovation and investment. So to sum up, if we tax the ever loving hell out of ground rent, George says we'll see the following benefits: Make housing much more affordable
May 10, 2023 · Original source
The picture on the left is Manhattan Island, NY. The picture on the right is Conanicut Island, RI. Both islands are about the same size, the same climate, the same distance from the mainland. Both are near good natural harbors. In 1600, some early European explorer would have considered them basically interchangeable. Still, the cost of housing in Manhattan is about $2000/sqft, and the cost of housing in Conanicut is about $500/sqft. Why? God didn’t create these two islands with different land value; something must have happened to make one 4x as expensive as the other. The obvious answer is “the Dutch chose to build their colonial capital on Manhattan, more and more people moved in, it became ever denser and more urban in a virtuous cycle, now it is very dense and urban, and, in the current regulatory regime, dense urban areas have higher housing prices than empty rural ones.” If back in 1624 the Dutch had decided to build their capital on Conanicut, maybe today it would be a city of 10 million people, and Manhattan would be an empty rural area. In that case, I would expect Conanicut to have 4x the house price of Manhattan. If I were a Native American living on Manhattan, and I was committed to keeping housing prices there low, I would ask the Dutch to build their capital on Conanicut instead. In fact, whenever a European came to my island seeking to build houses, I would try to fight them off. If I somehow succeeded at this for four hundred years, and Manhattan remained an empty rural area, then I would expect Manhattan prices to be much lower than they are now. So in response to all of your comments that I don’t understand basic causal inference, I answer that history provides quasi-experiments, and no, I’m pretty sure that Manhattan has high prices because lots of people moved there, rather than because of some other factor. Or, rather, both density and desirability feed into the other, but the density step is a crucial input. 2. Comments About Jobs And Amenities (And Not Density Per Se) Producing Desirability But Martin Blank writes: NYC/SF are expensive because there are MANY good jobs there and people WANT to live there. Not because of the density of housing. You could build 500,000 homes in the middle of your empty field in North Dakota, and it wouldn't do much for the demand there. You aren't going to create Manhattan by magicking 3.5 million housing units of similar quality into the Red Lake Indian reservation in Northern Minnesota. I originally found the various comments saying this annoying. Yes, there are many good jobs in NYC. You can be a barista at Starbucks, you can be an actor on Broadway, you can be a train conductor for the MTA. But why is it easier to be a barista in NYC than in North Dakota? Surely because there are millions of people in New York, those people drink a lot of coffee, and so they need a lot of baristas. Likewise, they watch a lot of plays, and ride a lot of trains, so they need actors and train conductors. If all the residents moved to North Dakota, there would be lots of demand for baristas, actors, and train conductors in North Dakota, and none in NYC. But some people gave versions of this argument that I found harder to dismiss. JSwiffer writes: The key fact your missing is if you wave a magic wand and 10x San Francisco you wouldn't 10x all jobs. You would 10x the # of waiters, and garbage men but you wouldn't 10x the # of 500k/yr Google site reliability engineers. And it's the latter not the former that are driving up prices. Other commenters analogized this to factory or coal mining towns. Here’s how I ended up thinking about this: suppose someone strikes oil in an uninhabited part of North Dakota, enough to produce 1,000 good oilman jobs. 1,000 oilmen move to the area and start a town. Because there are no NIMBYs, they build 1,000 houses. Each oilman creates demand for a certain amount of waiters (to serve them food), doctors (to treat their illnesses), teachers (to teach their children), etc. How many waiters, doctors, teachers, etc move to the town? Assume for the sake of argument that all jobs earn the same salary, $50,000. In that case, it has to be fewer than 1,000. Each oilman earns $50,000, and some of that gets spent on taxes and out-of-town goods. So he has less than $50,000 to spent on in-town goods and services, so (in this hypothetical) creates less than one other job. Each waiter needs doctors to treat their illnesses and teachers to teach their children, so each service employee creates some number of additional service employee jobs. Makeshift housing in a North Dakota oil boom town (source) If each person creates half a job, the original 1,000 oilmen attract 500 service workers, those 500 attract another 250, and so on until population stabilizes at 2,000 people. In this model, if there are fewer than 2,000 houses in the town, demand exceeds supply (no matter what is going on in the rest of the country), but if there are more than 2,000, supply exceeds demand. So if we imagine Google’s presence as an oil-like resource, the extra demand for housing in the Bay should gradually decline: at some point, you will have finished housing the Google workers and the service workers who support them. But this isn’t right either, because Google isn’t a natural resource - it’s a company founded by Bay Area residents. If you got more Bay Area residents, you would (with some delay) get more Googles. Or: Austin gets lots of jobs from Tesla. Tesla wasn’t founded by Austinites. But it moved to Austin when it became a known “tech hub”, ie a place with lots of tech companies and tech employees. It wouldn’t have moved to Austin if Austin was still an uninhabited plain or a one-horse town. So as Austin got bigger, it attracted more tech companies. So in both the Bay Area case and the Austin case, having more people attracted more tech companies, either because the residents themselves found the company or because the company gets attracted to this newly bustling city. Potential counterargument: Each new Bay Area resident gives the Bay another lottery ticket to found the next Google. If having the first Google gets it an extra 1 million people, but there are 300 million people in the US, then those extra 1 million only give it a 1/300 chance of winning the next lottery. So even though the Bay Area won the lottery once, and this made it have high demand, this doesn’t mean the high demand will cause it to win more lotteries. If you win the lottery once, spend all your winnings on more lottery tickets, and keep doing this forever, you haven’t invented an infinite money printing machine, eventually you’ll just lose. Potential counter-counter-argument: the Bay got Google, and Facebook, and Apple, and . . . so these can’t all be separate lotteries. I think you should probably model it as a high-level lottery to become the next hub of a tech-sized industry, plus many low-level lotteries where once you’re the tech hub, you’re attracting lots of techies, and each techie gives you a ticket in a lottery where the denominator is the number of techies to found the next big tech company. And the Bay might have half the US’s techie population. So maybe here there is a self-sustaining lottery-winning cycle, at least until tech plays itself out and nobody wants any more tech companies. And that might take a long time. Tom (author of Tom Thought) writes: The primary drivers of demand for living in NYC are the specific opportunities available in NYC. It is true that on long time horizons, one of the reasons these opportunities have tended to collect in NYC is that it is a dense place. But those aren't the only reasons - NYC is much more important than other, bigger cities in other parts of the world for complex historical reasons. Even if a catastrophe were to wipe out half the city, there would still be a great deal of demand to live near important institutions like Broadway, Wall Street, Port of NY & NJ, Columbia, etc (assuming those institutions survived the catastrophe). Increasing the number of housing units has a very mechanical impact on how many people can live in the place. But it has only a second-order impact on the types of institutions that drive demand to live in the city. People don't just generically crave to live near other people for the most part (a handful of urbanist freaks like myself excepted). The Bay Area is a great example of this. It is much less populated than other much cheaper cities. Density isn't why people want to live there - it's access to a specific culture and specific institutions. Demand for that is not simply a function of density - some people want to be part of Bay Area culture and others don't. Adding more units will induce some demand as a second-order effect, but will bring prices down as a first-order effect. To relate this to your model: we might be able to say that the country has a certain number of abstract "culture points" that have been allocated to different cities by various historical forces. Each culture point a city has increases demand to live in that city by a certain amount. Adding more people to the city may allow it to generate additional culture points over time, or acquire culture points from other cities, but this doesn't happen right away, and is determined by a host of factors other than just density. Under this model, we expect a place like NYC to always cost much more than North Dakota (since NYC possesses a large number of culture points), but we would also expect that adding additional housing units to NYC would bring costs down (since there are now additional housing units per culture point). Perhaps this process will over time allow NYC to steal away some culture points from Chicago, Boston, or other cities, but this is a secondary effect. This just seems to be passing the buck. Yes, people move to New York because it has Broadway, Columbia University, and Wall Street. Why does it have those things? Because one in every X New York citizens founds a good artistic/educations/financial institution, and New York has a large population of employees to work at those institutions and customers to patronize those institutions. If Conanicut Island had a population of 10 million people instead of Manhattan, there would be lots of great institutions on Conanicut and it would have more culture points. I don’t think it’s a culture-point game and population/density just sort of occasionally redistributes culture points, I think to a first approximation culture points just track population/density. Maybe they track the population/density of upper class people better than the total population/density, but I don’t think this is a big enough distinction to sink the argument. 3. Comments About Chinese Ghost Cities Some people brought these up as a good natural experiment: the Chinese really did try building millions of houses on their equivalent of a North Dakota plain. What happened? Jeremiah Johnson (author of Infinite Scroll) writes: You currently seem like you're at the stage of understanding the thought experiments pretty well, but not understanding them on a DEEP level. For example with your hypothetical, this has actually happened before! Kind of. China built a bunch of 'ghost cities' basically out of nothing, and while there was an initial craze of speculation and tons of investment and building... nobody went to live in those cities most of the time. And now they're deeply distressed assets worth basically nothing. When nobody actually lives in the ghost city, it doesn't matter that they have super dense housing. There's no demand. (the only reason they might be worth something is that the CCP very, very much does not want to pop their huge housing bubble and is likely to bail out some of the parties involved) Parmenides (author of Last House On The Left) writes: I think your mixing up the agglomeration effects of density, which is what induces the demand, and the housing supply. You can't just build a city and expect people to move in, China has tried that. But if you have the agglomeration effects of density and shortage of housing due to artificial constraints, which we have all across the US, then you get dense areas with high housing costs. sdwr writes: Think of China's ghost cities / apartment blocks. Prices surely can't be that high there. Maybe the answer is that developers are good at their job, and build supply where theres demand for it? But several other people object that although the Western press made a big deal about Chinese ghost cities a few years ago, it mostly just took a couple of years for people to move in, and now at least some of them seem to be thriving. For example, Michael quotes the Wikipedia article, Under-occupied Developments In China: Reporting in 2018, Shepard noted that "Today, China’s so-called ghost cities that were so prevalently showcased in 2013 and 2014 are no longer global intrigues. They have filled up to the point of being functioning, normal cities". Ash Lael writes: I'm sceptical of the Chinese "ghost city" phenomenon. I haven't explored the issue rigorously but my impression is that in areas that were previously dismissed as "ghost cities" like Ordos Kangbashi, the population is now large and growing. I think we in the west are so used to infrastructure bottlenecks and short sightedness and anti-construction policies that the idea of it being possible to build the housing and infrastructure to accomodate expected demand ten years in the future is completely foreign to us. Perhaps building brand new cities before they are even needed is what the YIMBY utopia looks like. See also Bloomberg: China’s Ghost Cities Are Finally Stirring To Life After Years Of Empty Streets. This wasn’t trivial. It looks like the Chinese government had to put in some work to make people move in, including opening good schools and universities there. Probably if they had just built apartments in the middle of the desert and nothing else, they would have stayed empty. But that’s even more of a reductio ad absurdum than the original ghost city plan. Kangbashi, China’s most famous ghost city. What are housing prices like in the ghost city? Again from Bloomberg: Sitting on the southern outskirts of Inner Mongolia’s Ordos City (population 2.2 million), Kangbashi was the archetypal ghost city 10 years ago, with barren boulevards and empty buildings standing forlornly in the desert. Local officials are adamant that things have changed. They say 91% of homes in the district are occupied. In fact, after a yearslong construction freeze, the government approved six housing projects in 2020 and expects 3,000 homes to be built by the end of this year. Apartments in a new development are selling for 9,500 yuan per square meter, and downtown they go for 15,000 to 16,000 yuan, according to Liu Yueyue, 28, a salesman at a new residential development in the district’s northeast. “Would houses in a ghost town sell at such high prices?” asks Liu. Half of his customers come from outside Kangbashi, and most are parents who want to send their children to the well-regarded local schools, he says. Looking at this list of real estate prices across Chinese cities, Kangbashi seems squarely in the middle - for example, Wuhan and Xian are also in the 15,000 - 16,000 range. I claim this supports my argument: surely twenty years ago, houses in this particular deserted corner of Inner Mongolia would have been dirt cheap (if any even existed). But if you build a city there, it becomes just as expensive as any other city! Here it’s very obvious that the density caused the high prices instead of the other way around. Still, the Chinese housing market is weird, with significant vacancies even in expensive, well-developed cities. Paul Botts: No official vacancy rates are published in China and no specific definition of it exists there. Various think tanks and researchers both within that country and elsewhere have published estimates ranging from as low as 11 percent to as high as 24 percent. Those estimates have been for varying samples of Chinese cities, have used various definitions of housing vacancy rate, etc. The best (as in most systematic) estimate yet produced has come from researchers at a university in Liaoning. They used night-time urban lightsheds captured by a new (2018 launch) Chinese satellite having a new level of light sensing technology which allows separating out light from parks and plazas. They covered a large sample (49 cities), and made their sample representative of city type, city size, regions within China, etc. They also crossed-referenced with local housing data to ensure accurate balancing of their sample and to confirm that the satellite was successfully identifying light coming from housing blocks. They found vacancy rates of just under 20 percent in China's Tier 1 cities, and found rates above 20 percent in 40 of the 49 cities. They found the highest vacancy rates in western and northeastern cities, which are also the newest ones; that finding is consistent with the hypothesis of significant numbers of recently-built ghost cities. https://www.researchgate.net/publication/345092218_Housing_Vacancy_Rate_in_Major_Cities_in_China_Perspectives_from_Nighttime_Light_Data And Phil H (author of the blog Tang Poetry) writes: The price of housing in China has skyrocketed over the past few decades, as all those extra apartments have been built. I live in a pleasant but unremarkable southern city, and I paid London prices (about 4.5m yuan/$650k for a 1,300 sq ft flat). That seems to match Scott's hypothesis that high density leads to high prices. House prices here have risen much faster than incomes. They've risen in rural areas, too, but the increases in price in cities have been stratospheric. 4. Comments Accusing Me Of Not Considering Tokyo, Even Though I Included A Section In The Post On Why I Didn’t Think Tokyo Was Relevant I won’t name and shame people, but for example: You excluded Tokyo from your dataset. Tokyo has much higher density than SF and much lower price per sqft. Tokyo just kills this. Tokyo is bigger than New York and has significantly lower rent because they build more housing! This is in a wealthy country with even lower interest rates than the US. I don't think you have justified excluding non-US metros, like Tokyo, or Auckland. Doesn't this lead to the natural conclusion that there is a sufficient level of housing to build, and that the problem is that the USA's many metros are structured to prevent housing? It seems like you're just arguing that US metros are bad at building housing, which is also what Matt Yglesias is arguing. "Change my mind about housing, but don't mention Tokyo" is like saying "Change my mind about gun possession, but don't mention Switzerland." You can't test the effect of allowing new housing unless you're willing to look at cities that do, in fact, allow it. Tokyo and NYC both attract tons of new residents But Tokyo's housing rents have been stable, while NYC rents keep rising. Why? Tokyo has permissive housing construction laws. NYC makes building new housing almost illegal. Yes, dense cities are attractive, and that makes them get more dense over time. But it only makes them more expensive if you forbid new housing to keep up with the new residents. Tokyo! But I’m like the 10th person to bring it up… As I wrote on the original post (not even edited in! it’s been there the whole time!): I worry someone will bring up Tokyo as a counterexample. But I think Tokyo managed to build its way to low housing prices in the context of the rest of Japan also having good housing policy. Even if that isn’t true, Tokyo on its own is a quarter of the Japanese market, so it might be able to exhaust the entire pool of Japanese house-seekers by itself! That is, yes, you’re all correct that cities are only expensive in the context of more demand for city housing than the (NIMBY-constrained) city housing market can currently supply. You are all correct that if this problem were solved at the national level, then city housing would be cheap, and every additional city house would make it cheaper. My claim is that marginal changes - like Oakland building an extra 10,000 units, but everyone else staying the same - will most likely increase Oakland prices. Yes, if Oakland unilaterally built 50 million units, that would soak up the entire excess demand and probably lower prices everywhere (including Oakland). Yes, if the entire US switched to good housing policy at the same time, that would probably lower prices everywhere (including Oakland). But if we don’t do any of that stuff, and just build another 10,000 houses in Oakland, I think it would probably increase prices in Oakland. Some other people brought up that Japan has a declining population, and it’s much easier to have low house prices when your population is declining (compared to some previous time when number of houses presumably matched number of people), but ddd pointed out that people continue to migrate from the Japanese countryside to Tokyo, so its population continues to increase. Also, Mike (I’m stitching together two comments here): In a country with a declining population, you would expect that fewer homes are being built per capita because there's little to no competition for existing homes. But it's exactly the opposite! Japan builds far more homes per capita than the US does, despite their declining population […] As a result, the average Japanese home is very new and the average house is torn down and replaced after a relatively short 30 years. They're living in nice new homes for cheaper. 5. Comments Accusing Me Of Not Understanding Economics Maximum Limelihood Estimator writes: I think you're making a very common mistake here of confusing supply/demand with *quantity* supplied or quantity demanded. (This is very common! we teach students about this in micro 101 because it's so easy to make!) What you're seeing is that the quantity supplied is correlated with housing prices (true!). But this is very different from establishing that the supply curve--i.e. the amount of housing that would be produced at any given price, and what moves up/down when we regulate/deregulate supply--is positively correlated with price. Figuring out what supply curves look like is a lot less intuitive and requires some high-grade econometrics, which is why economists had to set up a whole commission just to study this particular problem (the Cowles Commission). In terms of resources for understanding how these concepts are different, a micro 101 textbook will cover this distinction. For the econometrics side of this, I've heard good things about Scott Cunningham's *Causal Inference Mixtape*, although I haven't personally used it. My claim is that increasing density within a city shifts the demand curve for housing within that city, because of increasing desirability. MLE later gets more on point: The effect you're discussing here is kind of real in a sense. When the marginal utility of housing increases for *other* people, density arguably becomes more desirable for me, which is kind of like the demand curve shifting up. These are called bandwagon goods and discussed here: http://econfac.bsu.edu/research/workingpapers/bsuecwp200804gisser.pdf In theory, the bandwagon effect could be so strong that parts of the demand curve are upward-sloping. Solutions like this are not, technically, prohibited by the laws of mathematics, just the laws of economics. (And arguably of physics--see paper for conditions where these kinds of bandwagon effects imply the amount of housing in the city would have to be negative). In practice, this effect exists but just can't overcome the normal, non-weird economics that says "making more of a good makes the prices fall." Again, I claim the existence of Manhattan vs. Conanicut shows that sometimes it does. I cannot find the words “housing”, “real estate”, or “land value” anywhere in that paper. Alex Poterack writes: There's two things going on here: confusing shifts in demand with movement along the demand curve, and getting causation backwards. You're assuming density causes prosperity, rather than prosperity causing density. There are ways the former can happen, but the bigger thing is that, for a wide range of historical reasons, you can make a lot of money in NYC and SF, so lots of people want to live there, so they get very dense. This is the prosperity shifting demand right, so at any given price, more people want to live there; this drives prices up, and they go higher the more fixed supply is. If you built a bunch of housing in Oakland, lots of people would move there because it's cheaper, which is movement along the demand curve; it's still the same number of people who want to live there at any price. Now, it's possible that the increased number of people living there makes the city more prosperous (this is the phenomenon of induced demand), which would shift demand right, but there are way more differences between NYC/SF and Oakland than just the density, so I don't think it would shift demand enough to offset this. In particular, if it's just a small increase in small, it's also a small increase in density, so there's almost no shift in demand (but there is movement along the curve). I still think this is missing my point, but I present it here in case anyone else is enlightened by it and wants to try further to convince me I’m making this mistake. 6. Comments By Famous People Who Potentially Have Good Opinions Scott Sumner is an economist and blogger; he writes: It is certainly the case that building more housing can make a city more desirable, and that this effect could be so strong that it overwhelms the price depressing impact of a greater quantity supplied. But studies suggest that this is not generally the case. Texas provides a nice case study. Among Texas’s big metro areas, Austin has the tightest restrictions on building and Houston is the most willing to allow dense infill development. Even though Houston is the larger city, house prices are far higher in Austin: Houston pretty much describes the “Oakland with more housing” outcome that Alexander views as somewhat far-fetched. Only in this case, it’s Austin with more housing. Alexander seems too quick to accept the, “If you build it they will come” idea—that you can build more housing and thereby boost demand so much that prices actually rise. I started the post with a graph of about 50 cities, showing a positive correlation between density and price. I’m having trouble seeing how Sumner’s point isn’t just “if you remove 48 of those cities and cherry-pick two, the relationship is negative”. My attempt to place Austin and Houston on the original graph, using Sumner’s data plus a few other things available online. Why weren’t they on there already? Maybe because the graph is metro areas and Sumner was talking about Austin and Houston as cities, but I’m not sure and agree this is confusing. Everyone knows Austin is more expensive than Houston because Austin is a trendy tech and culture hub and Houston isn’t (and relatedly, because Austin’s median family income is 50% higher than Houston’s). Unless someone wants to claim that its failure to build housing helped turn it into a trendy tech and culture hub, I don’t think there’s much point to this comparison. It’s true that Houston’s bigger size didn’t let it leapfrog over Austin to become a trendy tech and culture hub, which goes against some of what I claimed in the first part of this post. But I never claimed there would be a perfect 1-1 correlation between city size and trendiness, or that you could never find a pair of cities where one was bigger but the other was more trendy. Just that there would be a correlation. Moving on: Here’s the problem with this argument. It mixes up population change due to economic effects such as the benefits of agglomeration, with population changes due to regulatory changes such as less strict zoning. If you look at things this way, then the stylized facts work against Alexander’s argument. Over the past 50 years, increasingly strict zoning has reduced housing construction on big cities like New York and San Francisco. As a result, their populations have increased by less than in cities with less strict zoning, such as Houston. If Alexander were correct, then the price gap between the tightly controlled cities on the coast and the more laissez-faire cities of Middle America should have shrunk over time. Instead, the price gap has widened. New York and San Francisco were always more expensive than other cites, but with tighter zoning and less new construction the gap has become far wider. During the last fifty years, there was also deindustrialization and demographic sorting. This is just the Austin vs. Houston story all over again. Alexander is implicitly viewing this outcome as a “problem” for the city that builds more housing. They must sacrifice so that the rest of the country can gain. But in his scenario, Oakland is better off. Indeed if it were not better off, then why would more people choose to live in Oakland? In order for it to be true that building more housing boosts housing prices, it must also be true that the quality of existing houses (including neighborhood effects) rises by more than enough to offset the increase in supply. That means the new housing construction must make Oakland such a desirable place to live that the amenity effect overwhelms the quantity effect [...] Of course, economic change always has winners and losers. Here’s how I would describe the impact of allowing more housing construction in Oakland, in the unlikely event that this did raise housing prices: 1. America would benefit. 2. Oakland would benefit. 3. Poor people in America would benefit, in aggregate. 4. Affluent people in America would benefit, in aggregate. 5. Homeowners in Oakland would benefit. 6. Some renters in Oakland would benefit (from a more economically dynamic city.) 7. Some renters in Oakland would suffer from higher rents. In the much more likely case where new housing construction would lower prices, the impact described in #5 and #7 might reverse. Either way, there is no defensible argument for not building more housing in Oakland, regardless of the impact on price. If building more housing reduces its price, then there is a strong argument for allowing more housing construction. If building more housing raises its price, then the argument for more construction is even stronger. I agree with all this. Jeremiah Johnson is a co-founder of the Center for New Liberalism, host of the Neoliberal Podcast, and a YIMBY activist (not to be confused with Jeremiah “Liver-Eating” Johnson, who killed 300 Native Americans and ate their livers). He writes: Here's why you're wrong in a single sentence: Demand causes high prices, not new units. Prices are high in SF and NYC because those are desirable places to live for a huge number of people. People all over the country and the world would live there if they could, and prices reflect that. The fact that the densest cities are the most expensive is true. But the high prices are not caused by density - rather, the density and the high prices are both a consequence of crushingly high demand […] There's a feedback loop, but what matters here is the elasticity, which is less than one. We can measure this empirically. New housing lowers prices via the mechanism of adding supply, which is basic economics and how we expect markets to work. New housing could raise prices if it also made the city a more desirable place to live and shifted people's preferences, such that there was more demand to live there after the new housing is built. If you think it's unclear which of these effects would dominate, luckily we have empirical data that over and over and over shows adding housing supply does indeed lower prices on a local level. This is a fairly well established result that replicates well. edit: I'm actually thinking about drawing out the weighted DAG graphs here to make the conceptual stuff easier, but it would be pretty long. I'd love to do this as a guest post. I’m skeptical of the empirical results because they don’t match the much stronger “Manhattan vs. Conanicut island” empirical results, and if I try to think about why, the best explanation I can think of is that the Manhattan experiment has been going on longer (ie long enough for Manhattan’s extra residents to found businesses and institutions that attract new people). I’ve told him he can try pitching this guest post to me; in either case, I would be interested in seeing the graphs. Several other people also posted this graph that Johnson helped make famous: Hopefully by now you can predict my objection: the places in the southeast corner are mostly unfashionable red state Sun Belt cities; the places in the northwest corner are mostly trendy liberal coastal cities. My conclusion is that trendy liberal coastal cities are both more NIMBY and more desirable, and if you use this to draw any conclusions about housing policy you’ll just end up confused. But maybe I should take this same lesson to heart myself. Dense cities are mostly trendy liberal coastal cities; uninhabited tundra in North Dakota isn’t. Maybe the demand is just for trendy liberal coastal cities, and once you attain that status, extra density doesn’t matter that much. Maybe Oakland has already maxed out its “trendy liberal coastal city” status, and even if it became Manhattan-sized, it wouldn’t get any trendier, or would get trendier only with a long time lag. There are a few very trendy small coastal villages in California (think eg Sea Ranch); maybe these (rather than North Dakota) are the natural control group for San Francisco. I think they are still cheaper than SF, but maybe not by very much. Cameron Murray is a housing economist whose work some other commenters recommended; he also writes the blog Fresh Economic Thinking. He very kindly showed up and wrote: I think you are in general right that agglomeration effects are real, which is why bigger cities have higher value to residents. I agree that people move locations. But I think you can go a step further. If one city is growing faster and densifying, surely those people are not demanding homes in other cities and those cities build slower. This is part of the spatial equilibrium story that further makes claims about “build density and get cheap homes” less plausible. 7. My Final Thoughts + Poll Thanks to everyone who commented on this post and helped me refine my thoughts. I’m willing to concede the following points: It might be that only attracting the sort of educated people who found companies, universities, etc will make housing prices go up. Less educated people will take more jobs than they create and not ratchet up the city’s desirability level. (I’d previously told commenters talking about “gentrification” that it was irrelevant to the mechanism I was talking about here, but maybe it isn’t - maybe “gentrifiers” are the people creating more jobs and institutions than they consume, and so homes that attract them in particular will increase demand more than they increase supply? Maybe this discussion does reduce to the gentrification discussion?)
Starship

Starship is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between January 07, 2022 and September 18, 2023. The archive places it in contexts such as "If John has more time, I’m interested in knowing how Starship changes the equation"; "To do that we need to build a heavy lift rocket (Starship)". It most often appears alongside America, Chicxulub, Earth.

Article page
Starship
Mention count
2
Issue count
2
First seen
January 07, 2022
Last seen
September 18, 2023
January 07, 2022 · Original source
If John has more time, I’m interested in knowing how Starship changes the equation.
But also, Tech CEO kind of randomly builds a starship, complete with a 2,000 person passenger capacity and working cryosleep pods, in the space of six months. Was the starship peer-reviewed?
If some comet disassembly mission is run by a bunch of Nobel-winning scientists and led by a guy who builds starships as a hobby, I feel like asking “okay, but did he also do a Google search for ‘journal with low standards’ and then get Reviewer #3 to sign off on it?” is not a high bar.
September 18, 2023 · Original source
I understand the frustration... but my impression is that space exploration is one of the fields where very thorough, very systematic planning with very conservative change cycles is the most promising approach to get something that works at the first attempt - even if it takes longer and costs more than planned. Compare the JWST to the most recent "Starship" launch for illustration.
This would sound plausible, except that Musk has succeeded by doing the opposite. I think this is why so many people are in love with Musk: he’s proven that valuing good ideas, moving fast, and not having bureaucracy can work, sort of, in a weird little bubble of his own creation. Yeah, the first Starship exploded, but most people predict Starship will eventually work, and when it does it will be a much more impressive feat of engineering than JWST or anything else created the “proper” way.
Coming at the same issue from the bottom-up direction, technical ICs often don't have the context of the full strategic vision, and non-technical leaders often struggle to communicate it downwards in ways that are meaningful to the technical implementors. This is another thing Musk is better than almost anyone at; taking a lofty objective and chaining it down to an individual's role. I heard a SpaceX employee giving an answer in an interview like "Our mission is to become an inter-planetary species. To do that we must first colonize Mars. To do that we need to build a heavy lift rocket (Starship). To do that we need to build a more powerful engine. To build our new engine we need this valve assembly to work; my mission is to optimize this valve to X performance requirement".
statins

statins is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 23, 2021 and November 24, 2022. The archive places it in contexts such as "he is very skeptical of preventative medicine, where you give drugs (eg statins) to healthy people"; "We saw this with cholesterol and statins,". It most often appears alongside Britain, 2008 crisis, A Failure, But Not Of Prediction.

Article page
statins
Mention count
2
Issue count
2
First seen
March 23, 2021
Last seen
November 24, 2022
March 23, 2021 · Original source
This isn’t always true. Healthy people are fragile (increased variance can mostly make them worse), very sick people are antifragile (increased variance can mostly make them better). So it is reasonable to give a terminal cancer patient an experimental drug - the worst that happens is they die (which would happen anyway) and the best that happens is they recover - it's all upside and no downside. For the same reason, he is very skeptical of preventative medicine, where you give drugs (eg statins) to healthy people. To justify statins, you have to be both very sure the studies showing they work are right, and very sure the studies showing they don't have serious side effects are right.
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
tianeptine

tianeptine is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 25, 2021 and March 08, 2022. The archive places it in contexts such as "I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US"; "People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid". It most often appears alongside FDA, ketamine, serotonin.

Article page
tianeptine
Mention count
2
Issue count
2
First seen
May 25, 2021
Last seen
March 08, 2022
May 25, 2021 · Original source
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
March 08, 2022 · Original source
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
TikTok

TikTok is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between May 14, 2021 and May 15, 2025. The archive places it in contexts such as "TikTok-sponsored video telling me to stop scrolling"; "What about the age of TikTok and Instagram?". It most often appears alongside Amazon, YouTube, ACX survey.

Article page
TikTok
Mention count
2
Issue count
2
First seen
May 14, 2021
Last seen
May 15, 2025
May 14, 2021 · Original source
I was scrolling through TikTok videos a few weeks ago when I came across a TikTok-sponsored video telling me to stop scrolling and go outside. I was confused. Here I was, perfectly willing (nay, wanting) to spend hours watching dance routines and drawing tutorials I had no intention of copying, but TikTok wanted me to stop? Why? Shouldn’t they have been taking advantage of me to maximize “eyeballs,” “time per session,” and “user engagement”?
One explanation is that TikTok is a good corporate citizen that helps its users maintain responsible screen time habits. Another explanation comes from Natasha Dow Schüll’s excellent book Addiction by Design: Machine Gambling in Las Vegas (2012). Schüll talks about gambling machines, people who use them, and the addictions that develop between the two. I think the conclusions she draws are applicable not only to the gambling industry, but also to other peddlers of vice like TikTok.
I’ve felt the attraction of this dark flow when I’m searching for something to escape from real life for just an hour or two. For me, it takes the form of scrolling through a social media feed. It could be Facebook, Twitter, Reddit, TikTok, or YouTube. I don’t look for anything in particular. I just want the comfort of scrolling through endless meaningless content. Sometimes, I don’t even fully absorb the content. If you took my phone away from me and asked me to name five things I saw, I doubt I’d be able to answer. The content just flows through me while I escape into a zone where real life doesn’t matter.
May 15, 2025 · Original source
Wise words - in 2011, when SRTHMK was written. What about the age of TikTok and Instagram?
USDC

USDC is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between August 16, 2022 and March 03, 2026. The archive places it in contexts such as "Hedgehog Markets is a crypto betting site using USDC and Solana"; "MNX uses the stablecoin USDC". It most often appears alongside Kalshi, Manifold, Manifold Markets.

Article page
USDC
Mention count
2
Issue count
2
First seen
August 16, 2022
Last seen
March 03, 2026
August 16, 2022 · Original source
Hedgehog Markets is a crypto betting site using USDC and Solana. Most of its markets are about sports. I’m featuring them here because they are, as far as I know, the first group to do something I’ve been waiting for a long time - allow users to create real-money prediction markets.
March 03, 2026 · Original source
(the other technological sea change is that this is possible at all. Five years ago, cryptocurrency prediction markets were too complicated. In the late 2010s, a group called Augur raised $5 million for the project but never managed to create usable software. FTX flirted with prediction-like contracts but never got them off the ground even with all their billions. Polymarket was the first to really solve this, making $10 billion in the process, but even they were barely usable in the early days. But Stephen’s making MNX with his own money and a team of 1-2 people. He benefits partly from the vibecoding revolution, and partly from all of the billions of dollars spent on improving cryptocurrency rails - MNX uses the stablecoin USDC).
Visa

Visa is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 08, 2022 and February 14, 2023. The archive places it in contexts such as "the CEO of Visa is personally opposed to weird supplements"; "using normal microtransactions with Visa or Stripe or whatever". It most often appears alongside facebook, Twitter, ACX.

Article page
Visa
Mention count
2
Issue count
2
First seen
December 08, 2022
Last seen
February 14, 2023
December 08, 2022 · Original source
Recently I’ve seen this expand from sex work to erotic fiction to medical marijuana to expressing opinions dubbed “misinformation”. One weird supplement company I liked almost had to shut down, not because the government said anything they were selling was illegal, but because payment processors thought it was the kind of thing that someone wouldn’t like, and refused to take their money. I don’t think the CEO of Visa is personally opposed to weird supplements, I think it’s the same kind of soft government collusion that’s been revealed to be going on at Twitter and Facebook and everywhere else.
February 14, 2023 · Original source
You could probably solve both problems just by cutting out the cryptocurrency angle and using normal microtransactions with Visa or Stripe or whatever. I think there’s still a risk that “get paid for [thing related to dating]” seems too creepy and sex-work adjacent and respectable women might avoid it; maybe you should instead let the woman donate the money to a charity of her choice?
vitamin D

vitamin D is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 17, 2021 and November 25, 2021. The archive places it in contexts such as "vitamin D or azithromycin cured COVID this effectively"; "Big trial on Vitamin D for depression finds null result". It most often appears alongside ACE-2 receptor, ACSH, Ahmed et al.

Article page
vitamin D
Mention count
2
Issue count
2
First seen
November 17, 2021
Last seen
November 25, 2021
November 17, 2021 · Original source
Click to expand. # is how many people were in the smallest relevant group (eg if there were 20 people in placebo and 10 in ivermectin, it was 10). Dose is ivermectin dose x number of days. Tested w/ is what drugs were given alongside ivermectin; compare is what drugs were in the “placebo” group (I excluded some very common things like paracetamol). %-PCR7 is what percent of patients had a negative PCR test (indicating recovery) after 7 days (though if 7 wasn’t available, I accepted anything from 6-12); the (I) and (P) are ivermectin and placebo groups. R is the ratio - green if statistically significant, red otherwise. DaysPCR is how many days it took to get a negative PCR test. Days to -sym are how many days it took symptoms to resolve. -outc is some serious negative outcome in the study, either clinical worsening, hospitalization, or death. I was inconsistent which one I chose, trying to pick whichever I thought struck a balance between high sample size and severity. Since this was almost never significant, I made it blue if it favored ivermectin and orange if it favored placebo (which it never did; there is no orange). Lowest p is the lowest p-value in the study for one of the headline results. 1o+ is whether the primary outcome was positive or not. I made this very quickly and unprincipledly and I am sure there are a lot of errors; please forgive me. Of studies that included any of the endpoints I recorded, ivermectin had a statistically significant effect on the endpoint 13 times, and failed to reach significance 8 times. Of studies that named a specific primary endpoint, 9 found ivermectin affected it significantly, and 12 found it didn’t. But that’s still pretty good. And “doesn’t affect to a statistically significant degree” doesn’t mean it doesn’t work. It might just mean your study is too small for a real and important effect to achieve statistical significance. That’s why people do meta-analyses to combine studies. And the ivmmeta people say they did that and it was really impressive. All of this is still basically what things would look like if ivermectin worked. But of course we can’t give every study one vote. We’ve got to actually look at these and see which ones are good and which ones are bad. So, God help us, let’s go over all thirty of the ivermectin studies in this top panel of ivmmeta.com. (if you get bored of this, scroll down to the section called “The Analysis”) The Studies Elgazzar et al: This one isn’t on the table above, but we can’t start talking about the others until we get it out of the way. 600 Egyptian patients were randomized into six groups, including three that got ivermectin. The ivermectin groups did substantially better: for example, 2 vs. 20 deaths in ivermectin group 3 vs. non-ivermectin group 4. There were various other equally impressive outcomes. Unfortunately, it’s all false. Some epidemiologists and reporters were able to obtain the raw data (it was password-protected, but the password was “1234”), and it was pretty bizarre. Some patients appeared to have died before the trial started; others were arranged in groups of four such that it seemed like the authors had just copy-pasted the same four patients again and again. Probably either the study never happened, or at least the data were heavily edited afterwards. You can read more here. A lot of the apparent benefit of ivermectin in meta-analyses disappeared after taking out this paper (though remember, this isn’t even on the table at the top of the post, so it doesn’t directly affect that). Since the Elgazzar debacle, a group of researchers including Gideon Meyerowitz-Katz, Kyle Sheldrake, James Heathers, Nick Brown, Jack Lawrence, etc, have been trying to double-check as many other ivermectin studies as possible. At least three others - Samaha, Carvallo, and Niaee - have similar problems and have been retracted. Those studies were all removed before I screenshotted the table above, and they’re not on there. But everybody is pretty paranoid right now and looking for fraud a lot harder than they might be in normal situations. Moving on: Chowdury et al: Bangladeshi RCT. 60 patients in Group A got low-dose ivermectin plus the antibiotic doxycycline, 56 in Group B got hydroxychloroquine (another weird COVID treatment which most scientists think doesn’t work) plus the antibiotic azithromycin. No declared primary outcome. Ivermectin group got to negative PCR a little faster than the other (5.9 vs. 7 days) but it wasn’t statistically significant (p = 0.2). A couple of other non-statistically-significant things happened too. 2 controls were hospitalized, 0 ivermectin patients were. This is a boring study that got boring results, so nobody has felt the need to assassinate it, but if they did, it would probably focus on both groups getting various medications besides ivermectin. None of these other medications are believed to work, so I don’t really care about this, but you could tell a story where actually doxycycline works great at addressing associated bacterial pneumonias, or where HCQ causes lots of side effects and that makes the ivermectin group look good in comparison, or whatever. Espitia-Hernandez et al: Mexican trial which is probably not an RCT - all it says is that “patients were voluntarily allocated”. 28 ended up taking a cocktail of low-dose ivermectin, vitamin D, and azithromycin; 7 were controls. On day ten, everyone (!) in the experimental group was PCR negative; everyone (!) in the control group was still positive. Also, symptoms in the experimental group lasted an average of three days; in the control group, more like 10. These results make ivermectin look amazingly super-good, probably better than any other drug for any other disease, except maybe stuff like vitamins for treatment of vitamin deficiency. Any issues? We don’t know how patients were allocated, but they discuss patient characteristics and they don’t look different enough to produce this big an effect size. The experimental group got a lot of things other than ivermectin, but I would be equally surprised if vitamin D or azithromycin cured COVID this effectively. It deviated from its preregistration in basically every way possible, but you shouldn’t be able to get “every experimental patient tested negative when zero control patients did” by garden-of-forking-paths alone! But this has to be false, right? Even the other pro-ivermectin studies don’t show effects nearly this big. In all other studies combined, ivermectin patients took an average of 8 days to recover; in Espitia-Hernandez, they took 3. Also, it’s pretty weird that the entire control group had positive PCRs on day 10 - in most other studies, a majority of people had negative PCRs by day 7 or so, regardless of whether they were control or placebo. Everything about this is so shoddy that I can easily believe something went wrong here. I don’t have a great understanding of this one but I don’t trust it at all. Luckily it is small and non-randomized so it will be easy to ignore going forward. I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
November 25, 2021 · Original source
Boris Johnson (left) is 5’9, so the guy in the middle must be gigantic. Who is he? Looks like it’s Milo Djukanovic, President of Montenegro, who’s 6’6 (198 cm). Is he the tallest world leader? It seems like he’s tied with his colleague across the border, Serbian president Aleksandar Vucic. Why are Balkan leaders so tall? As usual, the answer is “genetics”. This article says: It has been noted that men from Herzegovina are taller on average than men in other places—the average male height is just over six feet...Putting all the data together, researchers concluded that the most likely cause of larger-than-average height of Herzegovinian men is lifestyle during the Paleolithic—men hunted large animals such as mammoth for survival—such a diet, heavy in protein, combined with small population densities, would have provided ideal conditions for height selection, resulting in increasingly taller men who passed the trait down through their I-M170 chromosome to future generations. Some sources note that they manage to beat the Dutch despite the latter country’s much higher human development index. The Dutch are probably tall through a combination of nature and nurture; Balkan people are tall through nature alone. 7: Eliezer Yudkowsky doesn’t need more ego boosts, but an idea he had a couple of years ago - using strings of bright lights to provide a better and brighter experience for Seasonal Affective Disorder sufferers than regular light boxes - spread from him to the rationalist community to the wider world, and has finally gotten tested in a formal study (see Acknowledgments section). Results seem vaguely positive: "SAD symptoms of both groups improved similarly and considerably...exploratory analyses indicate that a higher illuminance is associated with a larger symptom improvement in the BROAD light therapy group" 8: Percent of people who choose woke options on polls very tentatively and preliminarily seems to be going down post-Trump (h/t Richard Hanania). 9: Twitter conspiracy theories 10: Did you know: all those reconstructions of “how classical art would have looked with the original paint” are probably inaccurate. There is no reason to think the Greeks and Romans used garish technicolor hues on their statues; what evidence we have suggest they were good at shading, and the statues were probably colored very tastefully. 11: Complaints about how Karl Friston uses the term “Markov blanket” 12: Trevor Klee on the claim that cyclosporine patients don’t get dementia. Apparently there was a big study where basically nobody on the immunosuppressant cyclosporine ever got dementia, and there are some theoretical reasons why cyclosporine might prevent neurodegeneration. But another study found people on cyclosporine got dementia at the usual rate. I think in a situation like this you should have a really high prior on “the people who got the crazy result bungled their study somehow”, but I’m interested in hearing what other people think. 13: Also from Trevor: a history of fluvoxamine treatment for COVID. 14: To tide you over until the next book review contest, here is awanderingmind’s review of The Conquest Of Bread. 15: Claims: cnbc.com/2021/11/05/sam…\nft.com/content/dcb75a… (better article, but paywalled)","username":"moskov","name":"Dustin Moskovitz","profile_image_url":"","date":"Fri Nov 05 15:49:46 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":184,"like_count":1188,"impression_count":0,"expanded_url":{"url":"https://www.ft.com/content/dcb75a56-ca23-439c-96db-56483979bf34","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/80a58c96-c72f-4301-b571-aa9384f132bd_2400x1350.jpeg","title":"Subscribe to read | Financial Times","description":"News, analysis and comment from the Financial Times, the worldʼs leading global business publication","domain":"ft.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> 16: Big trial on Vitamin D for depression finds null result. Peter Attia tries to tear it apart here, but I am unconvinced, especially in the context of Vitamin D never working for any of the things people say it does besides the most boring aspects of bone health. 17: “California is actively considering the adoption of flawed and inequitable guidance on math curricula based on misleading data and inaccurate success metrics reported by San Francisco Unified School District (SFUSD)...Based on our review of the data, we found misleading, unsupported, and cherry-picked assertions of success for the new math program. We noted that overall test scores are down and enrollments in UC-approved advanced math classes have dropped as well.” It looks like San Francisco is trying the good old “lower standards, then when more kids meet the standards, claim your school reform plan worked” trick again. 18: A new study claims that self-reported “Long COVID” symptoms are more associated with believing you’ve had COVID than with actually having it (as measured by serologic testing), which sounds like pretty strong evidence that it’s psychsomatic. Expert reactions are mixed-to-negative, although the only one of these that doesn’t sound like excuse-making is Dr. Rossman’s about the unreliability of the tests. I haven’t confirmed test reliability stats but Philippe Lemoine also thinks this is a plausible confounder. 19: Noahpinion: What If Xi Jinping Just Isn’t That Competent? I appreciated this for making me think, and for underlining the extent of the difference between the Deng/Jiang/Hu era and what Xi’s doing. I especially appreciated this line, which I’d never thought about before: Xi presided over the end of China’s hypergrowth. To some extent this is not his fault. No country can grow at 10% forever, and there were many structural forces pushing downward on China’s numbers — the end of the demographic dividend, the exhaustion of rural surplus labor (the Lewis Turning Point), the saturation of export markets, and so on. But China is also slowing down earlier than South Korea, Taiwan, or Japan did in their day. China’s per capita GDP (at PPP) is still only about 1/3 that of a developed country, so if they stop catching up at about half of developed-country levels, that will not be a great showing. A big lesson of the past twenty years has been “actually liberal democracy isn’t necessary to reach developed-country status”, so it would be quite the twist if it turned out you needed liberal democracy to reach developed-country status. This gets pretty close to the great mystery of why some less-developed countries “catch up” and others don’t; whatever happens in China is going to be a really useful data point. 20: Variations on the fable of The Frog And The Scorpion. 21: You’ve probably heard about the University of Austin, the new project by a bunch of wokeness-critical academics to start a new university that won’t cancel people or force conformity (New York Post article, Politico article - these were the two least “you need to be super-outraged about this right now” articles I could find). Tyler Cowen and Larry Summers are involved; Steven Pinker was supposed to be but left for unclear reasons. My thoughts, in no particular order: Even forgetting the political aspect, attempts to start new universities are always welcome.
Walgreens

Walgreens is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between June 23, 2022 and May 26, 2023. The archive places it in contexts such as "Walgreens pretends to be concerned about shoplifting as part of a dastardly plot"; "pharmaceuticals that I buy from ... Walgreens". It most often appears alongside Boston, CVS, New York.

Article page
Walgreens
Mention count
2
Issue count
2
First seen
June 23, 2022
Last seen
May 26, 2023
June 23, 2022 · Original source
The very big spike at the end might be a change in reporting by one or two stores - you can find the argument here. But it does look like shoplifting went from about 125 incidents/month in the early 2010s to more like 250/month just before the pandemic. Why is this graph so different from the other one? It looks like the top one came from the Department of Justice, and the bottom one came from SFPD. I’m not sure why these report differently. When you multiply out by 800K people in SF, by 12 months/year, and 30ish days/month, the first graph corresponds to 4 shoplifting incidents per day, and the second to 6. As LouB’s analysis here points out, that seems suspiciously low for a city of 800,000 people where stores are constantly closing because of shoplifting. Maybe off by a factor of a few hundred from what we’d expect. LouB writes: The SFPD report only references shoplifting offenses that required SFPD officers to prepare an incident report. That means either the shoplifter fought security, committed additional crimes, or stole more than $950 worth of items. It’s not that SFPD’s report is erroneous, it’s just not a representative statistic. In a parallel statistic, SFPD only completes incident reports for traffic accidents when there is an injury. Therefore, thousands of noninjury accidents are handled civilly without SFPD reports the same way thousands of shoplifting offenses are handled without reports. An insurance company would not determine premium rates based solely on SFPD incident reports, nor should readers interpret SFPD shoplifting reports as anywhere near the total picture of the shoplifting epidemic in San Francisco. (this would also explain why one or two stores changing their reporting policy can produce a spike equal to everyone else in San Francisco combined) But comparing incident reports from 2010 to incident reports from 2020 should still be apples-to-apples, unless the likelihood of reporting any given incident changed in the meantime. Did it? This news article quotes a San Franciscan who says that when they try to report shoplifting incidents, the cops tell them not to because “it doesn’t make a difference”. If cops say that now more often than they used to, it would make all these statistics meaningless. (Applied Divinity Studies claims to have an argument that shows this can’t be true. It goes something like: if San Francisco was a better place to shoplift than its neighbors - eg Oakland - then shoplifters would leave Oakland to go to San Francisco, and we would see Oakland shoplifting rates falling. Oakland shoplifting rates are falling, but no more so than the rest of the state, so there can’t be increased tolerance for shoplifting in San Francisco. I find this dubious for many reasons. First of all, many of the same reasons shoplifting is up in San Francisco - like Prop 47 or soft-on-crime progressive policies - also apply to Oakland. Second, given that shoplifting fell massively everywhere because of the pandemic, it feels dubious to try to compare different cities; maybe one city had stricter pandemic lockdowns than others. Third, do criminals really shop around for friendly jurisdictions? If so, why are so many crimes like car break-ins, concentrated in “the bad part of town”? Why wouldn’t criminals leave the bad part of town for under-exploited areas with richer residents and less competition? Maybe criminals in fact aren’t very strategic or mobile? Maybe they don’t want to stand in the BART station and then take a half-hour train ride holding a bag of stolen goods?) Maybe a better argument against this being true is how stable the shoplifting rates have been over time. Wouldn’t it be weird if (let’s say) a tripling of the real shoplifting rates was matched by a third-ing of the reporting rates (rather than a halving or a quartering or whatever)? On the other hand, here’s Shellenberger with some helpful data: Some of this is probably because of Proposition 47, which made some forms of shoplifting punishable with citation rather than arrest (but wouldn’t that be a clear discontinuity rather than a gradual trend?) But overall it sure seems like shoplifting is being taken less seriously, which might encourage people to report less. Another statistic I see is that only 2.3% of shoplifting cases result in an arrest; I don’t know how this is different from the graph above with numbers in the 30s; maybe it involves different levels of what makes something a “case”. I accept that the data don’t consistently show a spike in shoplifting. But what’s the alternative? My patient who works in loss prevention in SF stores is lying to me? The nice elderly Chinese man who sold me my last pair of glasses and chatted to me about the rampant shoplifting in his mall was lying? The San Francisco police are lying? Walgreens pretends to be concerned about shoplifting as part of a dastardly plot to close a bunch of stores for no reason? Target and CVS pretend to care about shoplifting as part of a plot to restrict their stores’ opening hours for no reason? Every big store near me has suddenly gotten a security guard at the front as part of some corporate-sponsored jobs program? Maybe the conservative narrative that soft-on-crime San Francisco must be experiencing rising crime rates took on a life of its own. Maybe it infiltrated not just the usual suspects like the SF police unions, but even such supposedly-liberal bastions as the New York Times. Maybe lots of big corporations took advantage of the fake narrative to make unpopular business decisions they were planning on making anyway. And maybe ordinary San Franciscans, confronted with everyone telling them they were in a shoplifting epidemic, started paying more attention to security guards and petty criminals who had always been there, a sort of mass hallucination that gripped everyone in the city. I can’t rule this out. Americans thought crime was rising all throughout the early 2000s, when it was in fact way down. Or maybe some statistics that we already know are off by several orders of magnitude got off by an additional factor of two or so. I think this one is more likely, but I’m genuinely not sure. Other Crime From the Economist: The Center on Juvenile And Criminal Justice puts it even more starkly, arguing that “San Francisco’s ‘Crime Wave’ Is Just One Crime”: This are potentially susceptible to the same reporting bias as shoplifting. So what about homicide? Homicide is practically always reported and investigated, making it a gold standard in crime measurement. (source) Looks pretty good until 2019. I don’t expect to gain useful information post-2020; the pandemic and the post-George-Floyd murder surge will make it impossible to evaluate for local variation. What about compared to other places? For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
May 26, 2023 · Original source
Another theme that Davies frequently revisits throughout the book is the mechanisms that fraudsters use. There is a certain amount of "trust by proxy" that happens within every system: whenever I withdraw cash from an ATM or bank, I don't inspect each bill to ensure it's not a counterfeit, because I presume that the bank has already done that at some point (and I also assume that the bank is far better at detecting counterfeits than I am). Ditto for any pharmaceuticals that I buy from CVS or Walgreens (if I'm paying for the high cost of a highly-vetted drug supply chain, I might as well trust it).
warfarin

warfarin is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between February 05, 2021 and December 06, 2023. The archive places it in contexts such as "Drug 2 is warfarin, which causes 40,000 ER visits a year"; "Does this include warfarin, where getting the dose slightly wrong makes you bleed to death?". It most often appears alongside Adderall, anarcho-primitivists, Anthony Fauci.

Article page
warfarin
Mention count
2
Issue count
2
First seen
February 05, 2021
Last seen
December 06, 2023
February 05, 2021 · Original source
Drug 1 is aspirin. Drug 2 is warfarin, which causes 40,000 ER visits a year and is widely considered one of the most dangerous drugs in common use. I challenge anyone to figure out, using WebMD's side effects list alone, that warfarin is more dangerous than aspirin. I think this is because if WebMD said "aspirin is pretty safe and most people don't need to worry about it", people might use aspirin irresponsibly, die, and then their ghosts might sue WebMD. Or if WebMD said "warfarin can be dangerous, be careful with this one", people might refuse to take warfarin because "the Internet said it was dangerous", die of the stuff warfarin is supposed to treat, and then their ghosts might sue WebMD. WebMD solves this by never giving the tiniest shred of useful information to anybody.
December 06, 2023 · Original source
And if we eliminate prescriptions, are all medications freely available at the corner store? Does this include warfarin, where getting the dose slightly wrong makes you bleed to death? Does it include MAOIs, where eating cheese after use makes your blood vessels explode? Obviously you put these things on the label, but is it in bigger or smaller print than “this blood-vessel-exploding medication contains chemicals known to the state of California to cause cancer”? Don’t all reasonable people ignore labels because they’re useless? And who decides what side effects are so bad you need to put them on the label? (right now it’s the FDA)
WeChat

WeChat is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 28, 2022 and September 18, 2023. The archive places it in contexts such as "I posted the NPC joke in a language-related chat group on WeChat (China's F"; "„I posted the NPC joke in a language-related chat group on WeChat (China's Facebook)“"; "WeChat was created in a very specific Chinese context that simply doesn't translate to the US". It most often appears alongside China, Foreign Policy, Scott.

Article page
WeChat
Mention count
2
Issue count
2
First seen
April 28, 2022
Last seen
September 18, 2023
April 28, 2022 · Original source
I posted the NPC joke in a language-related chat group on WeChat (China's Facebook). There were no consequences for two days, because Chinese censors don't waste their time analyzing jokes in English language chat. But after a couple of days the American moderators of the group (resident in China, like me) decided to eject me from the group and break off all communication.
September 18, 2023 · Original source
I wrote a piece for Foriegn Policy about why the vision of an 'Everything App' in the US market is essentially impossible. WeChat was created in a very specific Chinese context that simply doesn't translate to the US
https://foreignpolicy.com/2023/07/31/elon-musk-wechat-twitter-x-united-states-everything-apps/
Wegovy

Wegovy is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 24, 2022 and November 30, 2022. The archive places it in contexts such as "this report claiming “20,000 weekly US prescriptions” of Wegovy"; "The FDA says Wegovy is indicated for obesity,"; "but Wegovy isn’t controlled". It most often appears alongside Canada, Eli Lilly, FDA.

Article page
Wegovy
Mention count
2
Issue count
2
First seen
November 24, 2022
Last seen
November 30, 2022
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
November 30, 2022 · Original source
Second, spending on Wegovy might not fully capture use of semaglutide for weight loss, because some people might be taking Ozempic primarily for weight loss benefits. Ozempic sales are huge, and it is a top-20 spending drug in Medicare. After the clinical trial was published showing sustained weight loss benefits from semaglutide, Ozempic sales growth accelerated (though sales were already growing fast). Even though Ozempic is approved for the diabetes indication, it makes sense that people would take it for weight loss, because (1) there is a big overlap between the obese and diabetic population and (2) Ozempic is more likely to be covered by insurance.
2) while I can’t speak to the legality of sourcing the active ingredient, preparing the compound is probably legally fine. Wegovy and Ozempic has been in a shortage state for nearly 2 years now. In cases of shortages, I CAN legally compound products, including those protected by a patent or otherwise theoretically available. Patient access comes first- if I can’t source a finished product due to the manufacturer not having adequate supply, I’m good. I have to maintain documentation of my inability to source the patented products or the otherwise available product, but this is accepted practice. See, for example, this week’s FDA GFI re: compounding amoxicillin suspension for kids.
Practical update. I recently found that some varieties of Blue Cross Blue Shield insurance (through the federal employee program, at least) will now cover Wegovy (Ozempic) for weight loss, starting in January 2023. https://www.fepblue.org/open-season/whats-new-2023
Wegovy®

Wegovy® is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 24, 2022 and March 12, 2025. The archive places it in contexts such as "In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®"; "Semaglutide (Ozempic®, Wegovy®, Rybelsus®)". It most often appears alongside Eli Lilly, Eli Lilly, FDA.

Article page
Wegovy®
Mention count
2
Issue count
2
First seen
November 24, 2022
Last seen
March 12, 2025
November 24, 2022 · Original source
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
March 12, 2025 · Original source
Semaglutide (Ozempic®, Wegovy®, Rybelsus®)
YouTube

YouTube is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between April 06, 2022 and December 17, 2024. The archive places it in contexts such as "Facebook, Google, YouTube, and Twitter were already blocked"; "blocking Russian YouTube channels". It most often appears alongside Google, NYT, Trump.

Article page
YouTube
Mention count
2
Issue count
2
First seen
April 06, 2022
Last seen
December 17, 2024
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
December 17, 2024 · Original source
2: Russia fines Google $20,000,000,000,000,000,000,000,000,000,000,000 for blocking Russian YouTube channels.
14: Tessa Barton tries to see how long she can go without learning the results of the US election (series of YouTube videos). The Manifold Market is a spoiler for the results but has some good discussion.
Yugo

Yugo is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 25, 2021 and June 12, 2024. The archive places it in contexts such as "Point A is Yugo (or if you know a more modern example of a terrible car company, use that)"; "a Yugo is inferior to a Cadillac". It most often appears alongside @VividVoid_, Amazon, Antifragile.

Article page
Yugo
Mention count
2
Issue count
2
First seen
March 25, 2021
Last seen
June 12, 2024
March 25, 2021 · Original source
What about Distribution 2? Now Point B is Tesla, making revolutionary new environmentally-friendly cars. In fact, let's say it's some super-Tesla that's even better than the real Tesla, plus their cars are affordable even for the poorest people. Point A is Yugo (or if you know a more modern example of a terrible car company, use that). Now which distribution would you rather have?
Distribution 2, definitely! You can buy the super-Tesla and be very happy, without ever worrying about Yugo. In fact, after a few years Yugo will go out of business, super-Tesla will dominate the market, and everyone will be very happy.
June 12, 2024 · Original source
(Some people will object that nobody is “genetically inferior”, because “inferior” means “worse in every possible way”, and nobody is worse in all ways - maybe the person with cystic fibrosis has a gene for great memory or something. But first of all, if we come up with a contrived example where this isn’t true - eg identical twins who have exactly the same genes, except one has a somatic mutation causing cystic fibrosis - I’m still reluctant to say the mutated twin is “genetically inferior”. And second of all, this isn’t how we use the word “inferior” anywhere else - we might say that eg a Yugo is inferior to a Cadillac, even if the Yugo is better on some trivial dimension like having a slightly longer tire life.)
zinc

zinc is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 23, 2021 and February 01, 2023. The archive places it in contexts such as "there are plausible arguments (though no proof) for a few less-used options like zinc"; "The control group (which they seem to think can also be called 'the white group') took zinc, paracetamol, and maybe azithromycin". It most often appears alongside Alexandros Marinos, Carvallo, COVID.

Article page
zinc
Mention count
2
Issue count
2
First seen
November 23, 2021
Last seen
February 01, 2023
November 23, 2021 · Original source
This is false and I don't know where they're getting it from. Corticosteroids, fluvoxamine, and Paxlovid seem provisionally great. I haven't looked into the monoclonal antibodies but if western health authorities say they're fine I have no reason to doubt that. I even think there are plausible arguments (though no proof) for a few less-used options like zinc.
February 01, 2023 · Original source
Gideon (correctly) phrased this as a non-sinister albeit potentially weird misstep by the study authors, but in trying to summarize Gideon, I (incorrectly) phrased it as a sinister attempt to inflate results. After looking into it, I think Alexandros is completely right and I was completely wrong. Although I sometimes get details wrong, this one was especially disappointing because I incorrectly tarnished the reputation of Biber et al and implicitly accused them of bad scientific practices, which they were not doing. I believed I was relaying an accusation by Gideon (who I trust), but I was wrong and he was not accusing them of that. I apologize to Biber et al, my readers, and everyone else involved in this. My only reservation is that I don’t want to say too strongly that Gideon’s critique is wrong: I haven’t looked through the study documents enough to say with certainty that Alexandros’ reanalysis of the protocol issues is correct (though the superficial check I’ve done looks that way). But my mistakes are completely separate from anything Gideon did and definitely real and egregious. Cadegiani et al (Alexandros 50% right) Flavio Cadegiani did several studies on ivermectin in Brazil; I edited this section in response to criticism by Marinos and others, but the earliest version I can find on archive.is (I can’t guarantee it was the first I wrote) said: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. Also in Cadegiani news: he apparently has the record for completing one of the fastest PhDs in Brazilian history (7 months), he was involved in a weird scandal where the Brazilian government tried to create a COVID recommendation app but it just recommended ivermectin to everybody regardless of what input it got, and he describes himself as: …the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . Which sounds great, except that it looks like most of this is that the control group had a shockingly high mortality rate, much higher than makes sense even in the context of severe COVID. I think the charitable explanation here is that he made this data up too. But the Brazilian Parliament seems to be going with an uncharitable explanation, seeing as they have recommended that Cadegiani be charged with crimes against humanity. Anyway, let’s not base anything important on the results of this study. You can find Alexandros’ full critique here, but again I’ll try to summarize it as best I can. Alexandros is unhappy with my portrayal of Cadegiani’s background. I cite details that make him look strange and maybe fake, but there are other details that make him seem more impressive, like that he won gold medals at a Brazilian Scientific Olympiad.
Carvallo said that zero people in the treatment group of his study got COVID, compared to 58% of people in the control group. This is a pretty implausibly big effect, even by the standards of other pro-ivermectin studies, although I don’t know if anyone else tried the exact same preventative protocol as Carvallo. I think this is a more nuanced story than Alexandros’ version where Buzzfeed just doesn’t know that sometimes studies happen at more than one hospital. Is fraud the best explanation? I think Alexandros thinks of Carvallo as just not keeping very good records, so he doesn’t have raw data, and probably mixed up his numbers a few times or gave false numbers, and didn’t have anything to send his collaborators when they asked. I think this is maybe possible, although it seems suspicious that he falsely said Dr. Lombardo was involved, falsely claimed the hospital involved was doing a different trial, and got very implausible results. I can imagine weird chains of events that would cause all of these things through honest misunderstandings. But they don’t seem like the best explanation. After discussing this with Alexandros, he objects to my use of the term “known fraudster”. Perhaps I should have said “highly credibly suspected fraudster” instead, although in a Bayesian sense nothing can ever be 100% and at some point plausibility shades imperceptibly into knowledge. Still, I feel like my description here was more accurate than Alexandros’, which just mentions the hospital approval issue and says nothing about any of the rest of this in a thousand word subsection about this study in particular. I did err in saying the Carvallo paper was retracted. According to the article: After BuzzFeed News raised questions about how the study’s data was collected and analyzed, a representative from the Journal of Biomedical Research and Clinical Investigation, which published the results, said late Monday, “We will remove the paper temporarily.” A link was removed from the table of contents — but was reinstated by Thursday. The journal’s explanation, provided after this story was published, was that the author “informed us that he has already provided the evidence of his study to the media.” I apologize for the error. Elalfy et al (still disagree with Alexandros) I described this as: As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable […] There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. In the summary post, Alexandros’ entire criticism of my coverage of this trial, one of the seven trials he focuses on as most unfairly covered and uses as the lynchpin of his argument that I am morally culpable for disastrously bad reporting, is: [Elalfy et al] are accused of incompetence for failing to randomize their groups multiple times in Scott’s piece. The paper writes in six separate places that it is not reporting on a randomized trial, amongst them on a diagram that Scott included in his own essay. Hard to imagine how else they could have made it clear. In his full post on this, he goes line by line to point out all the places they say they are non-randomized, pausing to snark about how dumb I am for not noticing each time4. But he never addresses the actual source of my confusion, which is the part of the paper where it says that: Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment. If this was done as described, it should be an (almost) random trial; patients who come in on Wednesdays shouldn’t systematically differ from patients who come in on Thursdays5. But in fact, it looks (assuming I am understanding a very ambiguous table correctly) like there are very large pre-existing differences between the groups, sufficient to explain the entire result. If they in fact followed their days-of-the-week protocol, and it was random as expected, then I’m misunderstanding the table seeming to show very large differences, and they have indeed found evidence for ivermectin’s efficacy. If they didn’t follow their day-of-the-week protocol and it’s non-random, then maybe I’m understanding the table correctly and their groups had large differences to begin with and the fact that they had large differences at the end of the trial doesn’t demonstrate anything about ivermectin. This is all I was trying to say in the post, and instead of having any opinion on it Alexandros just makes fun of me for saying it. I think our actual crux is that Alexandros thinks a table of big differences between the groups has to be post-treatment (based on how big the differences are), whereas I’m not sure (because it’s unclear in the study, and also because the authors describe what could be a randomization method but also go on and on about how nonrandom they are). This is why I thought it mattered how random it was! Maybe instead of mocking me for this, you can admit it’s an important and relevant question! Ghauri et al (still disagree with Alexandros) I describe this as: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. Alexandros notes that these are three differences between experimental/control groups, out of 33 listed characteristics that could have been different. There is approximately a 23% chance (he calculates) that you could get these differences by chance. He accuses me of failing to do a formal Carlisle test - the usual test you would use to determine whether weird differences between randomized groups are because of fraud - instead eyeballing it and getting it wrong. Here I do want to defend myself: I am not accusing Ghauri et al of fraud. In fact, this would be nonsensical: they admit they are assigning patients nonrandomly. Carlisle tests are usually done to show that something about group assignment is impossible (and therefore fraudulent) in a fair random assignment. But these people aren’t claiming to have done a fair random assignment, so I’m not sure what a Carlisle test would prove. My argument is more like: this is nonrandom, therefore we should expect it to be unfair. It is unnecessary, but helpful, to note an actual apparent unfairness - there’s some evidence they gave the ivermectin to less severe patients (as measured by corticosteroid use). Therefore, we can’t necessarily trust this to be a fair trial (which it was never really claiming to be). In the end I kept Ghauri as an okay study, although GMK didn’t so it ended out trashed in the final analysis anyway. I think my thinking was that I never claimed to be only looking at RCTs, so this non-RCT whose between-group-differences confirmed that it was indeed a non-RCT with all the risk of bias that entails, didn’t necessarily need to be ruled out. Still, I don’t think I was wrong to mention this possibility, and I think Alexandros was wrong to suggest that I needed to do extra tests for this to be fair. Borody et al (still disagree with Alexandros) I described this as: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. Alexandros lists his full concerns here. My summary: Scott is being incredibly disrespectful to the authors, who are in fact a legendary gastroenterologist who invented life-saving h. pylori therapy and a brilliant immunologist who invented a well-regarded bronchitis vaccine (in particular, in describing their control group, I said “this is not how you control group, @#!% you”.
Zofran

Zofran is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between December 22, 2023 and August 22, 2024. The archive places it in contexts such as "I’m surprised more people don’t name their children after Zofran®"; "Tell your friendly on-staff doctor to prescribe a compounded Ozempic + Zofran (anti-nausea drug) pill". It most often appears alongside 23andme, ACX, Adderall.

Article page
Zofran
Mention count
2
Issue count
2
First seen
December 22, 2023
Last seen
August 22, 2024
December 22, 2023 · Original source
A month later - including a hunt through the kitchen to cleanse it of any shred of onion, or anything that had ever touched an onion - we agreed that actually, morning sickness was bad. Two months later, we debated bringing my wife to the ER because she hadn’t eaten anything other than plain saltine crackers in several days. We did manage to avoid the hospital, but it was rough. I’m surprised more people don’t name their children after Zofran®. Women get such positive feelings about it, right when they’re considering baby names. For a girl, you could nickname her Zoe. For a boy, Frank.
August 22, 2024 · Original source
Tell your friendly on-staff doctor to prescribe a compounded Ozempic + Zofran (anti-nausea drug) pill, and to say that it’s “medically necessary”. This is balderdash - the patient could always just take the two pills separately - but everyone is reluctant to challenge doctors about what’s really “medically necessary” or not.
zuranolone

zuranolone is a recurring brand in the Astral Codex Ten archive, appearing 2 times across 2 issues between March 08, 2022 and March 16, 2022. The archive places it in contexts such as "The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well"; "It’s Zulresso and Zuranolone"; "chemical difference between zuranolone and brexanolone". It most often appears alongside allopregnanolone, GABA, GABA-A Receptor.

Article page
zuranolone
Mention count
2
Issue count
2
First seen
March 08, 2022
Last seen
March 16, 2022
March 08, 2022 · Original source
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Zuranolone gets FDA approval for major depression: 15%
March 16, 2022 · Original source
Thanks to everyone who commented on Zounds! It’s Zulresso and Zuranolone and on the followup Progesterone Megadoses Might Be A Cheap Zulresso Substitute. I’m constantly impressed by the expertise of commenters here and on how much better the biomedical comment threads are compared to some of the others. Among the things I learned:
— Metacelsus (who writes the blog De Novo) doubts the price estimates I posted:
— Douglas (who writes the blog A Mindful Monkey) clears up some mechanism details I missed:
2,4-dinitrophenol

2,4-dinitrophenol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 02, 2021 and March 02, 2021. The archive places it in contexts such as "It contained 2,4-dinitrophenol, a mitochondrial uncoupling agent". It most often appears alongside 1938 FDA, 2,4-dinitrophenol, ADP/ATP carrier.

Reference entry
2,4-dinitrophenol
Mention count
1
Issue count
1
First seen
March 02, 2021
Last seen
March 02, 2021
March 02, 2021 · Original source
In the 1930s, a shady outfit called Isabella Laboratories made a popular over-the-counter diet pill called Formula 281 (slogan: "281 for the too weighty one"). If you're familiar with any of: the 1930s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?". Actually, no! It contained 2,4-dinitrophenol, a mitochondrial uncoupling agent.
So after 1938, US dieters stopped using 2,4-dinitrophenol. It next shows up in history books on the Eastern Front of World War 2, where Soviet soldiers would - I can’t believe I’m writing this - take it to keep warm. There’s something quintessentially Russian about this, like a cross between the Platonic essences of AK-47s and Krokodil. Still, World War 2 ended and poor DNP vanished from the history books again.
Whenever British tabloids, Vice, and the FDA all hate a thing, I’m inclined to feel at least a little fondness towards it. So is there a case for 2,4-dinitrophenol? I think the case would look like: sure, it has a very low therapeutic index. Sure, if you take just a few times the recommended dose, you could die. But if you very carefully take exactly the recommended dose, you probably won’t. You could give it out like methadone, in a way that makes it impossible to overdose. Patients might still get cataracts. But cataracts are treatable, or at least more treatable than some of the complications of obesity.
23andMe

23andMe is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 31, 2025 and July 31, 2025. The archive places it in contexts such as "Nucleus had previously offered 23andMe style genetic tests for adults". It most often appears alongside 23andme, Alex Young, anorexia.

Reference entry
23andMe
Mention count
1
Issue count
1
First seen
July 31, 2025
Last seen
July 31, 2025
July 31, 2025 · Original source
Last month, a startup called Nucleus took the plunge. They had previously offered 23andMe style genetic tests for adults. Now they announced a partnership with Genomic Prediction focusing on embryos. Although GP would continue to only test for health outcomes, you could forward the raw data from GP to Nucleus, and Nucleus would predict extra traits, including height, BMI, eye color, hair color, ADHD, IQ, and even handedness.
286

286 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 27, 2023 and April 27, 2023. The archive places it in contexts such as "owning hardware C64 ->8088 ->286". It most often appears alongside 8088, Adorno, Ant-Man.

Reference entry
286
Mention count
1
Issue count
1
First seen
April 27, 2023
Last seen
April 27, 2023
April 27, 2023 · Original source
...is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, G...
5-HTP

5-HTP is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Zembrin probably works better than 5-HTP"; "Zembrin probably works better than 5-HTP or St. John’s Wort". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, amitriptyline.

Reference entry
5-HTP
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
Tryptophan is a chemical found in food (especially eggs, seeds, and milk). In the body, it gets turned into 5-hydroxytryptophan (5-HTP) and then 5-hydroxytryptamine (5-HT), aka serotonin. Serotonin is an important mood regulatory chemical which we often try to increase during depression treatment, but if you consume serotonin directly, your body won’t be able to absorb it. The closest you can do is consume tryptophan or 5-HTP, and trust your body to absorb it and convert it into serotonin. Both of these chemicals are used for depression, and the few studies that have been done are mostly positive, for example this 2002 meta-analysis by Cochrane Collaboration. A more recent study finds 5-HTP works approximately as well as traditional antidepressants. Everyone agrees these studies are weak and low-quality and we can’t be sure of anything yet, but welcome to the world of depression supplementation. Early concerns about this potentially causing severe eosinophilic reactions don’t seem to have panned out, and might have been based on defective manufacturing processes which have since been fixed. A reasonable dose of 5-HTP would be to start at 100 mg daily, then go up to 200 and finally 300 mg daily after a few weeks. Don’t take this with any other serotonin-related medications without clearing it by your doctor first. You can find a reasonable brand of 5-HTP here.
Regimen 1B: Person with no access to a doctor, low time/energy budget: Take 5-HTP 100 mg, increase after one week to 200 mg, increase after three weeks to 300 mg. If that doesn’t work, stop 5-HTP, wait one week, start St. John’s Wort, 900 mg daily, for one month. If that doesn’t work, you may need to either get a doctor or increase the time/energy budget you’re willing to commit.
55-gal drum

55-gal drum is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "a scaled-up, ruggedized version built around a 55-gal drum". It most often appears alongside 538, 750k horny men, About Here.

Reference entry
55-gal drum
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#39: Portable Urinal For Disabled Adults 1 in 3 adults over 30 wake two or more times to pee each night, and 70% of them are bothered by this. 1 in 7 US adults have a mobility disability. Yuri is a portable urinal that sits next to a bed, couch, or desk to eliminate wakeful or painful walks to the bathroom. It is a funnel, drain trap, and vented holding tank on wheels, and it does not smell. Emptying is infrequent, and is done by a graywater pump that connects to the tank and empties into an existing drain, like a sink, toilet, or shower. Yuri could help a lot of people who don’t move well in the 70%+ of voidings that are urine-only. My name is Matt Voda, and I am a programmer-turned-maker working on Yuri full-time. I’ve prototyped five versions of it so far and am close to an MVP. Future paths include a scaled-up, ruggedized version built around a 55-gal drum for places and people without plumbing, and a Roomba-esque wheelbase and docking station capable of pumping itself empty. Seeking mentors who can advise on the industrial design of the unit, how to engineer it for manufacturing, and the development and compliance of medical devices. Please also reach out if you or a loved one want to receive a unit at-cost in exchange for feedback on how to improve it. Email m@ttvoda.com
747

747 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2023 and June 07, 2023. The archive places it in contexts such as "world leaders - iPhones, 747s, GPTs - are mostly still designed in the US". It most often appears alongside America, America Against America, American.

Reference entry
747
Mention count
1
Issue count
1
First seen
June 07, 2023
Last seen
June 07, 2023
June 07, 2023 · Original source
So far. China hasn’t quite caught up to America. Their GDP per capita is still less than a quarter of ours. Although they make many excellent products, the world leaders - iPhones, 747s, GPTs - are mostly still designed in the US, even if Chinese factories churn out the parts. Other Asian tigers like South Korea and Taiwan liberalized politically around the point where they started approaching developed-country GDP; in his analysis of their rise, Joe Studwell suggests that this might have been a necessary component. And Japan, despite all the virtues that made Wang think they would overtake the US, has stagnated instead.
8088

8088 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 27, 2023 and April 27, 2023. The archive places it in contexts such as "owning hardware C64 ->8088 ->286". It most often appears alongside 286, Adorno, Ant-Man.

Reference entry
8088
Mention count
1
Issue count
1
First seen
April 27, 2023
Last seen
April 27, 2023
April 27, 2023 · Original source
…where Sam fills in the northwest and southeast squares, then claims a correlation, draws a line, and points to high-status/deep-engagement as a single unified concept. But the southwest square could be “writes a wacky Shakespeare fanfiction, Romeo & Juliet II, in blank verse and period-appropriate language”, and the northeast square could be “publishes a dissertation on some irrelevant aspect of word frequency changes across English plays to prove something about linguistics”. And then having conflated these two things, he goes on to conflate a third thing, Shakespeare vs. Marvel. I’m not up to date on what goes on in academic literature departments, but Freddie de Boer says they’re increasingly offering “Spiderman Studies” classes in attempts to stay culturally relevant; probably Spiderman professors engage with Spiderman on the same deep level that Shakespeare professors engage with Shakespeare. If we made this a cube - high-status vs. low-status forms of engagement along one axis, Shakespeare vs. Spiderman along another axis, and deep vs. shallow engagement along the third - would anything be left of the “nerd” cluster as Sam describes it? I’m not sure. 2. Comments With Strong Opinions On The Definition Of Nerds, Geeks, Etc There were many of these. One common theme was that in the 70s, “nerd” was almost synonymous with “person who is only into unpopular things”, for example sci-fi, comics, and RPGs, all of which were unpopular in the 70s. Then those things became very popular, but the people who were interested in them still get called “nerds”. So now people like Kriss use “nerd” almost synonymously with “person who is only into popular things”. So we have a word which denotes either interest in unpopular things or interest in popular things, depending on who’s using it and when they last updated their lexicon. In the 70s, it was more reasonable to group “interested in math and computers” and “interested in sci-fi and RPGs” together, because both were unpopular and tended to involve the same group of socially maladept young men. Now math is still hard and unpopular; computers are hard in the sense that it’s tough to learn programming languages, but universally used and beloved; sci-fi and RPGs are very popular, and the typical sci-fi fan is closer to a socially-adept albeit “quirky” young woman. If words are hidden inferences, the inference represented by “nerd” - that sci-fi fandom, interest in math, interest in computers, maleness, poor social skills, and nonconformity with mainstream interests all go together - is now thoroughly false, dooming us to conversations like this one. Attempts to repurpose the several different words used to refer to the math/sci-fi/awkward/unpopular cluster to represent different aspects of its successor clusters have mostly failed. Sample comments from this section: Coagulopath writes: To me, being a nerd requires a degree of swimming against the cultural tide. It's weird and unpopular to be into trains, so the fact that you are indicates you have a bit of character (or are socially oblivious, which is also kind of endearing). The problem (and I think Kriss alludes to this) is that nerd stuff went mainstream in the past few decades. Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films. There's no longer any sense that nerds are the underdog. But what does it say about you when you wear a Star Wars shirt? You're pledging allegiance to the biggest, most popular club imaginable. Is that a brave stance? Those people always make me think "if you lived in the SW universe, you'd be on the side of the Empire". In general, I am creeped out by effusive public adoration for things that are near-universally loved. Like The Beatles. Or bacon. Or dogs. Or science (Neil DeGrasse Tyson's whole shtick). Regardless of how I feel about those things on the object level, there's no glory in joining a culture war when you're signing on to the winning side. Tolaughoftenandmuch writes: All this is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, Ghatanathoah writes: I also wouldn't say that nerd stuff only went mainstream in the last decade, it's not like the first 3 Star Wars movies were obscure arthouse pictures. I think the reason Marvel took off is just innovations in storytelling: movie producers finally figured out a way to adapt the gloriously arcane and convoluted lore of superhero comics in a way that could appeal to mainstream audiences in addition to nerds (much how George Lucas figured out how to get mainstream audiences to love the space operas nerds had been enjoying for decades before 1977). And Melvin writes: Comic book movies had always been pretty popular. Superman was the top grossing movie of 1979 despite coming out in 1978. Superman 2 was the second top grossing movie of 1981. Batman was the second top grossing movie of 1989. Batman Returns was the top grossing movie of 1992. Batman Forever was the top grossing movie of 1995. Spider-man was the third top grossing movie of 2002 (behind Lord of the Rings and Harry Potter movies). That's about all I can be bothered looking up right now but you get the idea, superhero movies have been popular since the 1970s. Kaitian writes: I think being a nerd requires being a bit socially clumsy about your interest, and talking or signalling about it in situations where most people don't expect it. So being a nerd about completely mainstream stuff like pop music or football is not possible, that's just fandom. Being a nerd about very well known and relatively well-respected stuff like classical music or birdwatching is rare, because most people who are classy enough to care about the thing in the first place are also classy enough to know when to shut up about it. But comics? Star trek? Power metal? They have fairly low barriers to entry *and* most people don't care about them, so there's plenty of opportunities to bring it up to people who don't want to hear about it. So that's why I think nerdery usually attaches itself to the typical targets. J.R. Leonard has as good a terminology proposal as anyone: I think what's missing is that Kriss uses "nerds" as his foil, but what he's talking about would better be described as fan culture. Deiseach teaches us the etymology of “geek”. The very distant etymology is from German gek, a relative of “cackle” → geck, a fool/madman (who was presumably cackling all the time). But this comes down to us through the early American institution of the geek show. From Wikipedia (cw: disturbing): Geek shows were an act in traveling carnivals and circuses of early America and were often part of a larger sideshow. The billed performer's act consisted of a single geek, who stood in the center ring to chase live chickens. It ended with the performer biting the chickens' heads off and swallowing them. The geek shows were often used as openers for what are commonly known as freak shows. It was a matter of pride among circus and carnival professionals not to have traveled with a troupe that included geeks. Geeks were often alcoholics or drug addicts, and paid with liquor – especially during Prohibition – or with narcotics. More obvious but I went surprisingly long without realizing it: “fan” (as in “sports fan”) is just short for fanatic. 3. Comments About Collecting The veteran collectors in the comments said that my theory (the Internet makes collecting too easy) was only a small part of the decline. The bigger part is that most coin collecting begins with the wonder of finding a rare coin in your change, and most stamp collecting begins with the wonder of finding a rare stamp on your mail, and the rise of credit cards and emails means people aren’t handling coins and stamps as much in their daily lives. Tom Metcalf writes: I'd guess many coin collectors got their start being patient enough to sort through change to see if they had e.g. a wheat cent or silver dime, but first of all, who pays with cash and gets change, and the chances of finding something collectible are orders of magnitude smaller than, say, the '90s. And stamp collectors would have started saving the stamps on mail sent to their house, but how frequently do you get stamped mail anymore? My 79-year old father goes to stamp shows, because one of his hobbies is to buy sheets of old but common unused stamps for less than face value. They are still valid postage, and then he uses them to personalize the stamps he puts on letters he sends to various people. And most of the other people at stamp shows are about his age. He does have some stamps he thinks are interesting that he's held onto, but the dealers at the stamp shows think they're common and uninteresting. So there's a decreasing number of stamps that might be "worth something" and a net loss of collectors in the hobby, and then every time a collector dies and his heirs have no interest in his collection and that many more stamps make their way to dealers who now have one less buyer. Too bad "sending paper letters with vintage but still valid stamps" never caught on with the hipsters. Art writes: The widespread adoption of email created a world where a letter is almost certainly junk mail or a bill. Nobody looks forward to hearing from a good friend from across the country now when picking up the day’s mail. If letters are not interesting why would stamps? The same for coins. Nobody uses cash, and getting a pile of coins with no significant value (inflation) is just an annoyance. These objects have passed into irrelevance. Still, it seems like some little pieces of joy and wonder have passed from our lives. Nathan Savir writes: I collect coins and I think the description of the hobby (and its putative death) isn't quite right. 1. Rare coins are in fact hard to find, even in today's internet world. They are usually sold in auctions, which might happen online, but still not that frequently. It's not unusual for examples some specific rare coin to be sold only once every few years. If the coin is also obscure, it may not be prohibitively expensive, so this kind of situation isn't the sole province of rich people. 2. One area of collecting is to get all the rare items. Another is to get all the minor varieties of a common item. These varieties may not be very rare, but it still takes a lot of effort to be able to distinguish them and to find them. Some collectors will obtain large numbers of relatively common coins and sort through and scrutinize them to try to identify interesting varieties. 3. An important part of collecting is getting good deals. This is surely a lot harder than it used to be because sellers can more easily figure out what things are worth and you won't find something grossly underpriced in a random antique store as often these days. But filtering through buckets (or online listings) of large numbers of coins can still be fun and lead to spotting good deals. So I think there is room in the hobby for nerd-like behavior (per your definition). I would argue the decline of the hobby is more due to competition from other similar hobbies (a generation ago you could collect stamps, coins, baseball cards, or rare books/comics - now you can collect beanie babies, Pokemon cards, NFTs, funko pops, action figures, etc.). I think stamps have suffered more than coins because stamp collecting has more of an aesthetic component (which has faced stronger competition) while coins have a historical element that is less well replicated by collecting newer things. This difference isn't obvious in the google trends graphs you posted but I believe is observable from looking at prices of stamps vs coins. I asked Nathan what coins he collects that are still tough to find, and he gave the example of this Yuan dynasty coin from 1350. I guess if you want to be a collector in 2023 you need to go hard. Arrk Mindmaster writes: I used to collect US coins from every denomination, year, mint, and variety (such as large and small date 1960 pennies). It was kind of like a treasure hunt, knowing you could find something in circulation that was actually more valuable than most people thought it was. I lost interest in the late 1980s sometime, when I found the volume of new coins dwarfed older coins. For example, for Lincoln pennies, they used to make a few million per year, then a few tens of millions. In the 80s, they started making about 5 BILLION each, and it started drowning out all of the old coins, which basically stayed the same value. This comment snapped some things into place for me; I collected coins as a kid in the 90s, and older coin collectors would talk as if you could spot some pretty rare things in your pocket change. But I had much worse luck, and it’s been years since I’ve even found a wheat cent in circulation (even when I was a kid this would happen occasionally). Maybe coin collecting is dying not just because we don’t use change, but because our change is less likely to have interesting coins in it. Another victim of mass money printing! The new state quarters sort of fix this, but other commenters express contempt for this. It feels like the transition between old myths (which one can enjoy) to the Marvel Cinematic Universe (which corporations are begging you to enjoy in a pre-approved way) - now that the Mint wants you to collect their coins, it feels kind of slavish to comply. Other people point out that the collecting of things other than stamps and coins is still going strong. Drethelin: Collecting has not in the slightest died out. People collect more things than ever, like sneakers, funko pops, vintage cars, guns, antique ceramics, anime figurines, magic cards, etc. Some people also brought up NFTs - are there lots of people who truly enjoy collecting NFTs, aren’t just in it for the investment value, and have kept up through the crypto bear market? 4. Comments Insisting That Sports Are Good Aris C writes: It's a little glib to dismiss sports as bad, isn't it? Athletes display extreme skill, sometimes transcendent. I don't think watching people push the limits of human ability is obviously bad. When I said sports were bad, I didn’t mean this as a final value judgment. I meant that, by our usual standards of entertainment, sports are bad. Imagine a sitcom which had several thousand episodes, each with the exact same plot (some people try to get a ball from one side of the court to the other). At some point, surely most people would stop watching! I appreciate the something something human spirit, and I’m happy to know that, somewhere in the world, sports are happening. It’s just the decision to actually watch them that confuses me. 5. Comments About Enjoying Things Vs. Building Identities Around Them Many people complained that some combination of me and/or Sam Kriss were denying that anyone can ever enjoy anything except as an attempt to “gain status”. I would answer first that yes, I think most behavior has some status component (although it may be a small component, mixed with genuine enjoyment). But also, it doesn’t seem mysterious that some people eg like Star Wars, or even love Star Wars. What seems mysterious to me is when this expresses itself as desire to buy thousands of dollars of figurines in the original boxes, or memorize the stats of every class of ship in the Imperial Navy, or something else which doesn’t seem very fun on its own merits. I’m not criticizing others from a place of invulnerability here. When I was ~14, I got really into Star Wars, and aside from reading all the Extended Universe books - some of which were genuinely very good - for about a year I spent all of my allowance and a good fraction of my free time obtaining Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing). My parents probably still have them somewhere. I cannot at all retrace what led me to do this, but I appreciate commenters’ less cynical explanations. For example, enchantingacacia writes: I think it's honestly sort of funny how non-nerds seem to genuinely not understand that a nerd's identity becomes about [thing] because they like it so much, not the other way around. Sometimes you encounter a thing—let's say it's Minecraft, because why not—and it's just such a positive experience for you that you take every possible opportunity to keep thinking about Minecraft, even when you're not playing. You collect every scrap of information you can find about Minecraft and you compose your own original Minecraft-related songs and you decorate your room with blocky little figurines. You get into a virtuous cycle where talking and thinking about Minecraft is so rewarding that you keep enjoying all these secondary activities long after you're bored of actually playing Minecraft itself. You look out for opportunities to meet people who'd enjoy talking about Minecraft with you and make a bunch of friends with whom you mostly talk about Minecraft, and your friends and family start seeing you as "the Minecraft guy" and they get you a Minecraft hoodie for Christmas cause they know it's a safe pick. This is the obvious and intuitive explanation! There's no need to get fake-deep about "ah, they got into Minecraft so they'd have something to construct their identity around": it explains nothing, and consistently makes incorrect predictions about the internal experiences of Minecraft nerds. It's only virtue is making people feel better about being annoyed by those weirdos who won't shut up about Minecraft. It's possibly that I have unusually low social motivation (genuinely, what does it mean to "construct your identity" and why is it something people would be this comically desperate to do?) and am typical-minding, but, uh, I wonder if there's any group closely associated with "nerds" who are also known for having low social motivation? I think it's a tad more likely that people like Kriss are typical-minding, and constructing elaborate social motivations for people who just like stuff regardless of what people like him think. This is a good comment which avoids buck-passing-style “I enjoy it because it’s fun” explanations. Along the same lines, odd anon writes: It is only among nerds that enthusiasm for something corresponds to learning more and more about it. That's the core element here. Non-nerds who like something do not feel any need to read up on it, to know more and more. Of course, the producers of content notice when their audience are nerds, and they start to produce content built more for those who obsessively learn every detail. Comics can start "rewarding" readers for noticing some obscure thing. A game series can have an elaborate continuity, or a zillion details to memorize. Content that either "leans into the fandom" or simply naturally has too much for non-nerds to easily pick up, can rapidly become nerd-only, thus solidifying boundaries. And sure, there are the personality correlations, attributes most nerds also have, including being STEM-y and lacking social skills. Combined, a nerd ended up being an unpopular thing to be. Ghatanathoah is less patient: Both Kriss' essay, and Scott's response to it, remind me of the "Evil Cannot Comprehend Good" trope from TV tropes, except replace "Evil" with "Very socially motivated people" and "Good" with "Less socially motivated people" (although honestly both sets have a lot of overlap). Both essays seem obsessed with finding some deep, social reason why hipsters and nerds behave the way they do, like the supervillain who is telling the hero that they are "Not So Different." They literally can't comprehend the idea that someone could actually like something, so they try desperately to find some way that liking things isn't something people actually do. People couldn't actually like Star Wars, sportsball, the MCU, or the Beatles, they must be liking them to achieve some social goal like forming an identity or seeking status! This is one of the two giant flawed assumptions that invalidates the theses of both articles (the other one, of course, is the assumption the the MCU is bad, when it is, in fact one of the human race's greatest artistic achievements*). If you assume that it is possible to like things for non-social reasons, or even in addition to social reasons, hipsters and nerds make much more sense. The reason that nerds like both popular stuff like the MCU, and less popular stuff like postage stamps is because they don't care about if something is popular, they care about if it fascinates them. Whether that thing is popular is orthogonal to how fascinating it is. That fascination makes them invest a lot of time and effort in it, which in turn makes it part of their identity. They weren't trying to find something to form and identity first and picking Star Wars, identity formation was just a side effect. Similarly, hipsters probably just get bored with things they see frequently and want to seek out new things to be interested in. Making obscure things part of their identity comes second, if at all. Also Ghatanathoah: Scott asks if its ever okay to build your identity around liking a thing. I would ask if it's ever okay not to? What's the alternative, building it around social status games or large nonselective identity groups? It seems to me that liking something isn't just a good thing to build your identity around, it's one of the best things to build it around. After all, unlike social status games, you can like something without forcing other people to not like it. This is a good question, well-phrased. I think the traditional answer is that you should build your identity around social relationships (I’m the son of X, husband of Y, friend of Z), career, and maybe a few hobbies. I agree with this as far as it goes, but it doesn’t work for a lot of practical tasks - I can’t get common ground with someone at a party or start a conversation by introducing myself as the son of X or husband of Y - most people just won’t know X or Y. Some people linked a Freddie de Boer post, Your Personality Has To Be Load-Bearing, which is generally good but I think has a similar problem. Obviously you should have a genuine and complex personality, but I worry a lot of people who talk about this will reject every specific aspect of personality because “it’s not, in itself, a full complex personality!”, but you can’t have a personality without building it out of specific aspects. A lot of people’s default personality, if they just do exactly what comes naturally and don’t put any effort into self-presentation or cultivation, is to browse Reddit and play video games. Most people realize this on some level and try to cultivate some personality beyond this, but I think that makes it extra unfair to say “Just use your natural true self!” The natural true self is exactly the boring thing we’re trying to get away from in favor of becoming a more interesting person. I’m trying to think if I have a personal answer to this. Part of my answer is the EA and rationalist communities. This has some downsides; I’m thinner-skinned about insults to these groups than I should be; some people might think I’m a fanatic. It also has some upsides; they embody real values I like, they try to make a difference in the world, they’re not consumer properties that make me feel like a corporation is pulling my strings. But my real answer is probably “I cheat by having a popular blog; this means you all know everything about me and I don’t have to fit my personality into a ten-second elevator pitch”. Maybe this is the traditional solution, from back when everyone knew everyone else in their community. It sure doesn’t feel adequate now, back when (non-bloggers) are constantly meeting strangers and having to communicate their identity to them quickly. My internal hierarchy of things it’s virtuous to build identity around, which is probably a weird class artifact and which I absolutely don’t consciously endorse, goes something like: Top-tier: Intellectual subfields, especially obscure ones or ones involving pure abstract math. If you can say “I’m really into trans-finite 8-dimensional Hoffdorf groups” and justify this with a discussion of how innately beautiful they are, you’ve got it made.
ACE inhibitors

ACE inhibitors is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 24, 2022 and November 24, 2022. The archive places it in contexts such as "with hypertension and ACE inhibitors,". It most often appears alongside ACE inhibitors, Adderall, Americans.

Reference entry
ACE inhibitors
Mention count
1
Issue count
1
First seen
November 24, 2022
Last seen
November 24, 2022
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Activision

Activision is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 02, 2022 and March 02, 2022. The archive places it in contexts such as "not for lack of trying by Activision". It most often appears alongside Frito-Lay Inc..

Reference entry
Activision
Mention count
1
Issue count
1
First seen
March 02, 2022
Last seen
March 02, 2022
March 02, 2022 · Original source
This is part of why I’m skeptical of a purely chemical definition of addiction, where addiction is what happens when some chemical that mimics a neurotransmitter “hijacks your reward center”, and so nonchemical addictions (eg video games, Internet) are by definition impossible and/or metaphorical. Yes, sometimes chemicals mimic neurotransmitters and hijack your reward center. But all that does is stimulate your reward center, the same way video games and potato chips stimulate it. Opioids can still stimulate your reward system more strongly than video games and potato chips can, but not for lack of trying by Activision and Frito-Lay Inc.
ACX

ACX is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 10, 2022 and April 10, 2022. The archive places it in contexts such as "I will be wearing an ACX T-shirt". It most often appears alongside 1022 High St. Blue House w/red porches, 11:11 Cafe, 1548 NE 15th Ave.

Reference entry
ACX
Mention count
1
Issue count
1
First seen
April 10, 2022
Last seen
April 10, 2022
April 10, 2022 · Original source
ROME, ITALY Contact: Luca Ciarrocca (luca.ciarrocca@gmail.com) Date: May 11 Time: 6:30 PM Coordinates: https://plus.codes/8FHJVFWC+5V Location: We'll meet at the Giordano Bruno statue in Campo de' Fiori and then sit at an outdoor bar there. I will be wearing an ACX T-shirt.
AdBlock

AdBlock is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2023 and June 28, 2023. The archive places it in contexts such as "There’s no easy way to block the element with AdBlock"; "If I can’t avoid it, I will turn on AdBlock for your site in particular to block the element". It most often appears alongside ACX, Bing, GMail.

Reference entry
AdBlock
Mention count
1
Issue count
1
First seen
June 28, 2023
Last seen
June 28, 2023
June 28, 2023 · Original source
As long as you keep typing, the “Saving Draft” button flashes in the upper left corner every few seconds. There’s no easy way to block the element with AdBlock without also removing important functional elements of the editor. And speaking of AdBlock, its interface looks like this: An unblockable moving status bar that switches every few seconds between different messages about the product! This is what they think the people most obsessed with blocking flashing/changing elements on websites want! This new “show a constantly-moving status bar on screen to tell you when they will change another flashing element” thing has also made it onto the front page of Bing, although luckily you can dismiss it there. I would have expected Google to resist. They haven’t. I can no longer write things on Gmail - I have to compose on Notepad and then copy-paste to the Gmail window - because they’ve made it look like this: It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
I hope this message reaches some of the people who work in interface design for tech companies. If your site does this, I hate you and will try to avoid using your product. If I can’t avoid it, I will turn on AdBlock for your site in particular to block the element (incidentally denying you revenue). If I can’t get AdBlock to block the offending element in particular, I’ll just hate you even harder, to make up for it.
ADIDAS

ADIDAS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 24, 2021 and February 24, 2021. The archive places it in contexts such as "a jacket that says ADIDAS in big letters". It most often appears alongside 1950s, 1980s, 1983.

Reference entry
ADIDAS
Mention count
1
Issue count
1
First seen
February 24, 2021
Last seen
February 24, 2021
February 24, 2021 · Original source
For example, apparently Super Bowl parties are a working-class custom. And apparently it's an middle-to-upper-middle-class custom to make fun of Super Bowl parties, either throwing them ironically or not at all. Even in 1983, Fussell describes "the satiric anti-Super Bowl party" among the middle class, where people deliberately get together on Super Bowl Sunday to conspicuously not watch sports and feel superior. This hits a little closer to home than the rhododendrons. Or: contempt for clothing with obvious brand names on it (eg a jacket that says ADIDAS in big letters) is apparently a middle-class reaction to a working-class preference for this sort of product. Or: your list of "grammatical pet peeves" is a suspiciously good match for the differences between the upper-middle-class dialect and the working class dialect (whether you keep a distinction between "less" and "fewer", for example). Also, I regret to inform you that the dead hand of Paul Fussell is reaching out all the way from 1983 to tell you that your contempt for people who overuse apostrophes is a class signaling game.
adrafinil

adrafinil is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 16, 2022 and November 16, 2022. The archive places it in contexts such as "recognized it as their company’s old brand of adrafinil". It most often appears alongside @AutismCapital, Adderall, ADHD.

Reference entry
adrafinil
Mention count
1
Issue count
1
First seen
November 16, 2022
Last seen
November 16, 2022
November 16, 2022 · Original source
Here the detectives on r/NootropicsDepot recognized it as their company’s old brand of adrafinil7. Adrafinil is a prodrug of modafinil, an unusual stimulant-like drug. That is, your body metabolizes adrafinil and turns it into modafinil after you take it.
Except - was he taking the selegiline and adrafinil at the same time?
aella.ai

aella.ai is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 28, 2023 and September 28, 2023. The archive places it in contexts such as "Aella is offering aella.ai , an “AI girlfriend” based on her". It most often appears alongside 2020 election, @eigenrobot, @jeremychrysler.

Reference entry
aella.ai
Mention count
1
Issue count
1
First seen
September 28, 2023
Last seen
September 28, 2023
September 28, 2023 · Original source
29: Re…lated? Blogger/model Aella is offering aella.ai, an “AI girlfriend” based on her, as the flagship product of a company (?) that will help influencers create AI chatbot girlfriends based on themselves. I haven’t seen a lot of uptake yet - my trollish theory, which I might explain more later, is that the real killer app will be AI boyfriends (horny men want sex, horny women want attention / emotional validation; which of these can chatbots more effectively fake?)
Aerocar

Aerocar is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 04, 2021 and June 04, 2021. The archive places it in contexts such as "already had an airworthiness certificate for the Aerocar". It most often appears alongside A.I.M., America, Astralcodexten Com.

Reference entry
Aerocar
Mention count
1
Issue count
1
First seen
June 04, 2021
Last seen
June 04, 2021
June 04, 2021 · Original source
Flying cars didn’t have the same issues; they were being developed privately. But regulation doomed them. Harold Pitcairn was almost successful in developing a flying car, but then in World War II the government nationalized his helicopter patents (they promised to give them back after the war, but reneged) and he spent the rest of his life in court. He won, 17 years after his death. Bruce Hallock had a promising design, but he sold a plane to a missionary group in Peru and was arrested as an “arms trafficker”. Robert Fulton had a successful prototype, “however, Fulton’s financial backers had become discouraged with the seemingly endless expense of meeting government production standards, and they withdrew their support.” Molt Taylor “was actually in serious negotiations with Ford as late as 1975 to have the Aerocar mass-produced. The monkeywrench was thrown into the negotiations by the FAA and the DOT. Taylor already had an airworthiness certificate for the Aerocar, granted by the CAA (predecessor of the FAA) after a delay of 7 years from its first flight. He claims that the agencies turned thumbs down on the Aerocar ‘because everybody would have one, and we couldn’t handle the [air] traffic.’ Airplane regulation has only gotten stricter: “The entire F.A.R. / A.I.M., which every airman is responsible for knowing, is 1085 pages long. At least it was in 2013; a new one comes out every year.” So in the end, we have none of these technologies. No flying cars, even though they were prototyped almost a hundred years ago. Some nuclear energy, but crippled, aged, feared, and hated. 3D printing, but no nanotech. No level 5. Because the state needs legibility, and progress is not legible. The bureaucratic incentives are to calcify. If no one does anything new, no one will do anything wrong. Hall:
Aerojet XLR-132

Aerojet XLR-132 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 07, 2022 and January 07, 2022. The archive places it in contexts such as "using one, three, and nine Aerojet XLR-132 engines". It most often appears alongside ACX Discord, Aimable, Alex.

Reference entry
Aerojet XLR-132
Mention count
1
Issue count
1
First seen
January 07, 2022
Last seen
January 07, 2022
January 07, 2022 · Original source
But, OK, let's assume I can design three optimized hypergolic upper stages using one, three, and nine Aerojet XLR-132 engines each and a mass fraction of 0.9, stack them one atop the other underneath the Falcon Heavy fairing, designed built and assembled in three months, and somehow the whole thing actually *works*, OK, that will boost a single W83 to 18 km/s hyperbolic excess velocity with 100 kg left over for the guidance, navigation, telemetry, and midcourse propulsion system. 18 km/s is not 20 km/s, but meh, close enough.
Aerolamp

Aerolamp is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 13, 2025 and October 13, 2025. The archive places it in contexts such as "Misha’s company Aerolamp has an early developer’s kit lamp on sale now". It most often appears alongside 2023, Aaron Silverbook, ACX Grants.

Reference entry
Aerolamp
Mention count
1
Issue count
1
First seen
October 13, 2025
Last seen
October 13, 2025
October 13, 2025 · Original source
Misha Gurevich, Vivian Belenky, and Rachel A, $50K, to manufacture far-UVC lamps. Far-UVC is a type of ultraviolet light that kills germs rapidly; in a room with correctly-installed far-UVC lighting, viruses and bacteria die before they can reach another host, and the spread of contagious diseases plummets. In a world where this technology reached its full potential, respiratory pandemics like flu and coronavirus would cease to occur. Until now, these lamps have been limited to a few research prototypes. Last year, an ACXG-sponsored study worked to establish that they are safe for human use; results were reassuring. The next step is to produce them at scale as a consumer product for use in schools, daycares, and houses. Misha’s company Aerolamp has an early developer’s kit lamp on sale now, and is looking to hire an industrial designer experienced in safety and compliance who can help them transition to a mass-manufacturable version. If that’s you, get in touch with them here. Misha is a personal friend and a longtime ACXG evaluator; due to conflict of interest, this grant is being covered in conjunction with an outside funder.
African ceramics

African ceramics is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 06, 2021 and May 06, 2021. The archive places it in contexts such as "African ceramics and African wines flooded in the market". It most often appears alongside 320 AD, 476 AD, Africa.

Reference entry
African ceramics
Mention count
1
Issue count
1
First seen
May 06, 2021
Last seen
May 06, 2021
May 06, 2021 · Original source
...ned prosperous. Vandal piracy brought in a great deal of treasury. “Freed from levies connected with the annona for Rome [the annual grain shipments for the Roman dole], African ceramics and African wines flooded in the market throughout the eastern Mediterranean.” Italy also remained somewhat prosperous. Italy peacefully moved from rule by an emperor to...
...ned prosperous. Vandal piracy brought in a great deal of treasury. “Freed from levies connected with the annona for Rome [the annual grain shipments for the Roman dole], African ceramics and African wines flooded in the market throughout the eastern Mediterranean.” Italy also remained somewhat prosperous. Italy peacefully moved from rule by an emperor to a Gothic king without the raiding and v...
African wines

African wines is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 06, 2021 and May 06, 2021. The archive places it in contexts such as "African ceramics and African wines flooded in the market". It most often appears alongside 320 AD, 476 AD, Africa.

Reference entry
African wines
Mention count
1
Issue count
1
First seen
May 06, 2021
Last seen
May 06, 2021
May 06, 2021 · Original source
The economic decline was not evenly spread. Vandal north Africa remained prosperous. Vandal piracy brought in a great deal of treasury. “Freed from levies connected with the annona for Rome [the annual grain shipments for the Roman dole], African ceramics and African wines flooded in the market throughout the eastern Mediterranean.”
Age of Empires 2

Age of Empires 2 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 24, 2024 and September 24, 2024. The archive places it in contexts such as "Playing Age of Empires 2". It most often appears alongside A Collection Of Unmitigated Pedantry, ACOU, ACOUP.

Reference entry
Age of Empires 2
Mention count
1
Issue count
1
First seen
September 24, 2024
Last seen
September 24, 2024
September 24, 2024 · Original source
Playing Age of Empires 2.
Air BnB

Air BnB is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "low-prospect twenty-somethings staying at Air BnBs". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Air BnB
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
First World economies will increasingly be marked by an Officialness Divide. Rich people, the government, and corporations will use formal, well-regulated, traditional institutions. Poor people (and to an increasing degree middle-class people) will use informal gig economies supported by Silicon Valley companies whose main skill is staying a step ahead of regulators. Think business travelers staying at the Hilton and riding taxis, vs. low-prospect twenty-somethings staying at Air BnBs and taking Ubers. As Obamacare collapses, health insurance will start turning into one of the formal, well-regulated, traditional institutions limited to college grads with good job prospects. What the unofficial version of health care will be remains to be seen. If past eras have been Stone Age, Bronze Age, Iron Age, Information Age, etc, the future may be the Ability-To-Circumvent-Regulations Age.
Airbnb

Airbnb is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "bring Airbnb to profitability". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Airbnb
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
The event that marked the turning point [for the founders of AirBnB] was the 2008 Democratic National Convention (DNC) in Denver, Colorado. The pair saw an opportunity to capitalize on the quadruple over-attended event that caused a massive shortage in rental housing. Finding hosts to offer up rooms in their houses was actually the easy part. Getting people to rent those rooms proved more difficult.
The DNC bump was great for business, but it only lasted a week. The founders were desperate for a way to extend the impact of the event. While sitting around their kitchen table one day, still extremely broke, they came up with the idea that would bring Airbnb to profitability: cereal.
— Pando
Airtable

Airtable is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Think Airtable+Vensim+Roam+Kumu". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Airtable
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#6: System Dynamics Simulator I'm Oleksandr Nikitin, and I want to build a system dynamics simulator. Enable independent researchers to simulate, forecast, and visualize metabolic pathways, epidemic spread, mass transit, ecology, macroeconomics, etc. Show, don't tell. Without code. Think Airtable+Vensim+Roam+Kumu, integrated and working offline. Why offline? Why simulate? Why a new tool? Complex systems must be simulated. You miss emergent phenomena if you analyze parts separately or simplify the details. Offline sets you free from distractions and groupthink. Free to make your own breakthroughs. Take your references, notes and data with you, dive deep, then return with the verified, reproducible, interactive model. Research can take years. Tools should outlast devices and app stores. And it must be fast. Isn’t it insane for a productivity tool to make you wait? I spent years on prototypes and algorithms, tested in companies since 2013, and now I want to put these experiments together. Not as a startup. As a tool accessible to everyone. The plan: create a community of curious inquisitive makers, empower them with a small fast and robust core app, iterate and grow together, augment the human intelligence even more, and understand the world. I seek funding to focus on this project full-time, for two years. To launch and to guide people to the finished research. Sounds inspiring? Worth the money? Want more details? Ping me at oleksandr@tvori.info. Also see https://cortex.substack.com/
AK-47

AK-47 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 29, 2024 and May 29, 2024. The archive places it in contexts such as "give the Crusaders AK-47s". It most often appears alongside @ElytraMithra, Aaron, ACX.

Reference entry
AK-47
Mention count
1
Issue count
1
First seen
May 29, 2024
Last seen
May 29, 2024
May 29, 2024 · Original source
Grant that if God exists, that makes it possible for a monk to levitate. But God usually sticks to the laws of nature. If He was going to violate them, you would think He would do it to save the Holocaust victims, or give the Crusaders AK-47s, not to let one weird monk levitate occasionally. Bulldog tries to salvage this by saying God is very committed to natural law except occasionally to bring people to the faith. But then why levitate a random monk in 1650, rather than have every Pope be constantly two inches off the ground? I think you’d have to claim that God will only violate the laws of Nature in cases that will bring a tiny number of people to the faith but leave the vast majority unmoved, which is such a weird preference that I think you can no longer call it a “prediction” of the “God exists” hypothesis.
albendazole

albendazole is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 28, 2021 and December 28, 2021. The archive places it in contexts such as "albendazole and mebendazole, the current choices for deworming". It most often appears alongside 1DaySooner, 2016 Washington carbon tax ballot initiative, @GoodSciProject.

Reference entry
albendazole
Mention count
1
Issue count
1
First seen
December 28, 2021
Last seen
December 28, 2021
December 28, 2021 · Original source
The Oxfendazole Development Group, $150,000, to develop oxfendazole. This is a next-generation antiparasitic drug which may one day replace albendazole and mebendazole, the current choices for deworming. Several hundred million children worldwide suffer from parasitic worm infections; this certainly affects their health, and a growing body of research suggests it might affect their cognitive ability, educational attainment, and future income. GiveWell endorses deworming as one of the most effective charitable interventions; the successful development of new antiparasitics would further this effort. Oxfendazole has done well in early studies and this group wants to follow them up in the hopes of eventually getting FDA approval. To learn more or send a donation, see this site
ALLO

ALLO is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "ALLO/zulresso mediates tonic GABA inhibitory tone". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, allopregnanolone.

Reference entry
ALLO
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
Thanks to everyone who commented on Zounds! It’s Zulresso and Zuranolone and on the followup Progesterone Megadoses Might Be A Cheap Zulresso Substitute. I’m constantly impressed by the expertise of commenters here and on how much better the biomedical comment threads are compared to some of the others. Among the things I learned:
— Metacelsus (who writes the blog De Novo) doubts the price estimates I posted:
— Douglas (who writes the blog A Mindful Monkey) clears up some mechanism details I missed:
Allo Munganga

Allo Munganga is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 13, 2025 and October 13, 2025. The archive places it in contexts such as "Allo Munganga, a telemedicine platform for the DRC". It most often appears alongside 2023, Aaron Silverbook, ACX Grants.

Reference entry
Allo Munganga
Mention count
1
Issue count
1
First seen
October 13, 2025
Last seen
October 13, 2025
October 13, 2025 · Original source
Manoj Nathwani, $12K, for Allo Munganga, a telemedicine platform for the DRC. There is ongoing conflict in East Congo, and “all physicians have fled after armed groups took over”. But there are still some working pharmacies and labs, and Manoj wants to pull together telemedicine infrastructure so patients can continue getting diagnoses, lab tests, and prescriptions. He has partnered with a local medical group and will be using our money to buy technology, pay salaries and offer free consultations to patients over the phone.
allopregnanolone

allopregnanolone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "the FDA approved allopregnanolone for post-partum depression". It most often appears alongside alcohol, allopregnanolone, Ativan.

Reference entry
allopregnanolone
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
Zulresso is the brand name of allopregnanolone (aka brexanolone), a new medication for post-partum depression. It’s interesting as a potential missing link between hormones and normal mood regulation.
Allopregnanolone is a naturally-occuring metabolite of the female hormone progesterone. In 1981, scientists found it was present in unusually high concentrations in the brain (including male brains), suggesting that maybe the brain was making it separately and using it for something.
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator! (or maybe that’s just an urban legend, I’ve never found proof either way) The discovery of endorphins (ie endogenous opiates) helped shed light on the brain’s reward system. So the discovery of a sort of endogenous benzodiazepine was pretty exciting. Maybe it’s some kind of master control switch for anxiety or something? Psychiatrists only know two ways to respond to an exciting new thing: publishing breathless studies claiming that it’s the true mechanism of action for SSRIs, and publishing breathless studies claiming that it’s the true biological basis of depression. This time, they did both: see eg Fluoxetine elevates allopregnanolone levels in female rat brain and The role of allopregnanolone in depressive-like behaviors. The basic theory was that stress / social isolation / etc → decreased allopregnanolone → something something BDNF and synaptogenesis → depression. And SSRIs → increased allopregnanolone → something something BDNF and synpatogenesis → recovery! Change the word “allopregnanolone”, and that’s every theory in psychiatry. But this particular theory had two extra pieces of evidence: premenstrual dysphoric disorder and postpartum depression. Remember, allopregananolone is a natural metabolite of the female hormone progesterone. Progesterone levels go up during pregnancy and the ~18th day of the menstrual cycle, then crash back down after delivery and the ~24th day of the menstrual cycle. Meanwhile, some women get depressed after delivering a baby, or on the ~24th day of their menstrual cycle. Suspicious! Maybe it’s because their progesterone was getting converted into allopregnanolone, an antidepressant hormone that affects mood! (why doesn’t every woman get PPD and PMDD? This study suggests that women with PMDD have altered sensitivity to allopregnanolone; plausibly people with PPD have some other form of altered sensitivity. In case you have the same question I do: the correlation between PMDD and PPD is not 100% but still pretty significant) History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Almonds

Almonds is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 21, 2025 and October 21, 2025. The archive places it in contexts such as "Americans spent $12 billion on almonds that same year". It most often appears alongside A16Z, AI safety movement, AIPAC.

Reference entry
Almonds
Mention count
1
Issue count
1
First seen
October 21, 2025
Last seen
October 21, 2025
October 21, 2025 · Original source
In my 2019 post Too Much Dark Money In Almonds, I asked: why is there so little money in politics?
During the 2018 election, Americans - candidates, parties, PACs, and small donors like you - spent a combined $5 billion pushing their preferred candidates. Although that sounds like a lot of money, Americans spent $12 billion on almonds that same year. Why the imbalance? The oil industry has strong political opinions, and they make $500 billion per year. Do they really think electing oil-friendly politicians isn’t worth 2% of revenue?
Alp Blossom

Alp Blossom is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom)". It most often appears alongside Alinea, Alpha Tolman, Amish.

Reference entry
Alp Blossom
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Which country has the world’s best health system? This is the type of question I usually love. I rank everything. I rank the 10 best meals I’ve ever had (#1 Alinea in Chicago, #2 Tanja Grandits in Basel, and #3 OCD in Tel Aviv). I rank chocolates (#1 Askinosie, #2 Dick Taylor of California, and #3 Fruition of New York. I rank Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom). I rank colleges. I rank academic departments of bioethics and health policy that compete with my own. I rank the meals I cook, the races I run, the bike rides I take, the speeches I give.
Alpha Reads

Alpha Reads is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Reading (Older kids are on "Alpha Reads")"; "Alpha Reads is excellent". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Alpha Reads
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Reading (Older kids are on “Alpha Reads”; younger kids use Amira and Lalio)
Leadership …and so many other things. 100% of MAP test questions are multiple choice. Where are the students learning deep thinking? What about the learning you get from small group discussions in a university seminar? I think Alpha’s answer to that concern is “that is what we do in the afternoon workshops”. I think that is a fine answer. How well do most schools teach those things as a baseline? Maybe Alpha does as good a job as other schools teaching public speaking. Maybe they do a better job? But what is missing is an objective measure of how well they do it. I can see that GT is making progress on the measurement of those softer skills by running workshops on “competitive academics” where the output is legible. The kids at that school don’t just learn to give talks, they give talks and then submit them to The Moth in an attempt to qualify for (and win) Storytelling Nights. They don’t just write persuasive essays graded by their teachers, they write persuasive essays and then submit them to national competitions. They don’t just learn the concepts of long term planning and strategy, they put them in practice playing go and chess and then compete against their peers and earn an elo ranking. I think it is a fair way to assess these things and leads to more accountability, but note that it is only happening at the GT school with ten kids, not the main Alpha campus, and the data points so far on whether it is working are very thin. Our friends at the flagship school are less convinced that the climbing wall workshop is teaching those “non-state mandated” academics that the core program misses. Another disappointment is “Alpha Writes”. The school was not happy with the third-party reading and writing apps out there and built their own. Alpha Reads is excellent. Alpha Writes (which is newer and just launched about a month ago) is not. I believe the school (and Joe Liemandt) understands that the product is not good enough, and they are taking it back to the drawing board, but for now I do not think the Alpha kids have any real edge versus traditional schools in their training on essay or creative writing skills. How do Alpha’s MAP score improvements compare to other selective private schools across the country? This is an important question for some parents. It is great if you can expect your 5th grader to advance 2.6x faster than they would at the local public school, but if you are planning to spend $40,000/year to send him to Alpha, your alternative is likely not the local public school. And if you are considering moving your family to Austin for the school, your alternative options are places like Horace Mann, Harvard-Westlake, and Lakeside. How does the 2.6x improvement that Alpha is delivering compare to those elite institutions? I have no idea. Unlike Alpha I have not found any elite school who has shared the MAP improvement rate for the students at their school. I expect these elite schools are very good for all the reasons the selective private school I sent my kids to before GT was good: They have a select group of peers, they have great teacher:student ratios, and they have incredible resources. I also expect most of these schools do NOT accelerate (I could very well be wrong here and would be happy to be corrected). If they are like the schools I am familiar with they allow their students to advance through the material at the “normal” pace, with the normal pedagogy, but, because those kids are so bright, that leaves them plenty of time for enrichment. Lakeside school (where Bill Gates’ children attended) has classes where students write and perform one-act plays at the school’s annual festival; advanced photography courses where students develop their own signature style and brand; Literature classes on Victorian novels, the Harlem Renaissance, and Chaos Theory; classes on abnormal psychology, architecture, blockchain, game theory and wilderness survival and leadership. I am sure by the time they graduate, students from Lakeside have learned much more than what is measured on a standardized MAP test. The problem is that it is difficult to measure those “extra things”, so you are left making the decision on vibes and prestige and marketing materials. (and meanwhile the objective numbers are held under lock and key by the elite schools themselves who have no incentive to share them when they are already winning on vibes). Is there any data on how different education programs are doing on improving MAP scores? I have not found any schools other than Alpha that share their data, but there are some “educational interventions” where the measured output was an improvement on MAP tests. Teach to One: Math is a math program used in some schools that is meant to be “personalized” using “technology-infused direct instruction”. Their studies find that students who follow their full program improve 23% faster on the math MAP scores, and students who are “exposed” to the program improve 12% faster. MAP Accelerator is a tool developed by Khan Academy. It claims that students who use it consistently for 30-minutes per week improve their MAP scores 9-43% faster than a control group. Both examples show that if you have technology-enabled personalized learning for extended periods of time improve MAP scores versus the norm. Both show that those results only happen when the students stick with the program. This shows that the “secret sauce” of Alpha’s 2-Hour Learning is not what and how they are teaching but rather: That they are using personalized technology-enhanced programing (when most schools aren’t)
Alpha Tolman

Alpha Tolman is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom)". It most often appears alongside Alinea, Alp Blossom, Amish.

Reference entry
Alpha Tolman
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Which country has the world’s best health system? This is the type of question I usually love. I rank everything. I rank the 10 best meals I’ve ever had (#1 Alinea in Chicago, #2 Tanja Grandits in Basel, and #3 OCD in Tel Aviv). I rank chocolates (#1 Askinosie, #2 Dick Taylor of California, and #3 Fruition of New York. I rank Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom). I rank colleges. I rank academic departments of bioethics and health policy that compete with my own. I rank the meals I cook, the races I run, the bike rides I take, the speeches I give.
Alpha Writes

Alpha Writes is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Alpha Writes (which is newer and just launched about a month ago) is not". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Alpha Writes
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Leadership …and so many other things. 100% of MAP test questions are multiple choice. Where are the students learning deep thinking? What about the learning you get from small group discussions in a university seminar? I think Alpha’s answer to that concern is “that is what we do in the afternoon workshops”. I think that is a fine answer. How well do most schools teach those things as a baseline? Maybe Alpha does as good a job as other schools teaching public speaking. Maybe they do a better job? But what is missing is an objective measure of how well they do it. I can see that GT is making progress on the measurement of those softer skills by running workshops on “competitive academics” where the output is legible. The kids at that school don’t just learn to give talks, they give talks and then submit them to The Moth in an attempt to qualify for (and win) Storytelling Nights. They don’t just write persuasive essays graded by their teachers, they write persuasive essays and then submit them to national competitions. They don’t just learn the concepts of long term planning and strategy, they put them in practice playing go and chess and then compete against their peers and earn an elo ranking. I think it is a fair way to assess these things and leads to more accountability, but note that it is only happening at the GT school with ten kids, not the main Alpha campus, and the data points so far on whether it is working are very thin. Our friends at the flagship school are less convinced that the climbing wall workshop is teaching those “non-state mandated” academics that the core program misses. Another disappointment is “Alpha Writes”. The school was not happy with the third-party reading and writing apps out there and built their own. Alpha Reads is excellent. Alpha Writes (which is newer and just launched about a month ago) is not. I believe the school (and Joe Liemandt) understands that the product is not good enough, and they are taking it back to the drawing board, but for now I do not think the Alpha kids have any real edge versus traditional schools in their training on essay or creative writing skills. How do Alpha’s MAP score improvements compare to other selective private schools across the country? This is an important question for some parents. It is great if you can expect your 5th grader to advance 2.6x faster than they would at the local public school, but if you are planning to spend $40,000/year to send him to Alpha, your alternative is likely not the local public school. And if you are considering moving your family to Austin for the school, your alternative options are places like Horace Mann, Harvard-Westlake, and Lakeside. How does the 2.6x improvement that Alpha is delivering compare to those elite institutions? I have no idea. Unlike Alpha I have not found any elite school who has shared the MAP improvement rate for the students at their school. I expect these elite schools are very good for all the reasons the selective private school I sent my kids to before GT was good: They have a select group of peers, they have great teacher:student ratios, and they have incredible resources. I also expect most of these schools do NOT accelerate (I could very well be wrong here and would be happy to be corrected). If they are like the schools I am familiar with they allow their students to advance through the material at the “normal” pace, with the normal pedagogy, but, because those kids are so bright, that leaves them plenty of time for enrichment. Lakeside school (where Bill Gates’ children attended) has classes where students write and perform one-act plays at the school’s annual festival; advanced photography courses where students develop their own signature style and brand; Literature classes on Victorian novels, the Harlem Renaissance, and Chaos Theory; classes on abnormal psychology, architecture, blockchain, game theory and wilderness survival and leadership. I am sure by the time they graduate, students from Lakeside have learned much more than what is measured on a standardized MAP test. The problem is that it is difficult to measure those “extra things”, so you are left making the decision on vibes and prestige and marketing materials. (and meanwhile the objective numbers are held under lock and key by the elite schools themselves who have no incentive to share them when they are already winning on vibes). Is there any data on how different education programs are doing on improving MAP scores? I have not found any schools other than Alpha that share their data, but there are some “educational interventions” where the measured output was an improvement on MAP tests. Teach to One: Math is a math program used in some schools that is meant to be “personalized” using “technology-infused direct instruction”. Their studies find that students who follow their full program improve 23% faster on the math MAP scores, and students who are “exposed” to the program improve 12% faster. MAP Accelerator is a tool developed by Khan Academy. It claims that students who use it consistently for 30-minutes per week improve their MAP scores 9-43% faster than a control group. Both examples show that if you have technology-enabled personalized learning for extended periods of time improve MAP scores versus the norm. Both show that those results only happen when the students stick with the program. This shows that the “secret sauce” of Alpha’s 2-Hour Learning is not what and how they are teaching but rather: That they are using personalized technology-enhanced programing (when most schools aren’t)
AlphaFold

AlphaFold is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2024 and September 18, 2024. The archive places it in contexts such as "AlphaFold solved the difficult scientific problem of protein folding". It most often appears alongside AIDER, Ajeya Cotra, Alan Turing.

Reference entry
AlphaFold
Mention count
1
Issue count
1
First seen
September 18, 2024
Last seen
September 18, 2024
September 18, 2024 · Original source
All these milestones have fallen in the most ambiguous way possible. GPT-4 can create excellent art and passable poetry, but it’s just sort of blending all human art into component parts until it understands them, then doing its own thing based on them. AlphaGeometry can invent novel proofs, but only for specific types of questions in a specific field, and not really proofs that anyone is interested in. AlphaFold solved the difficult scientific problem of protein folding, but it was “just mechanical”, spitting out the conformations of proteins the same way a traditional computer program spits out the digits of pi. Apparently the youth have all fallen in love with AI girlfriends and boyfriends on character.ai, but this only proves that the youth are horny and gullible.
AlphaGeometry

AlphaGeometry is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2024 and September 18, 2024. The archive places it in contexts such as "AlphaGeometry can invent novel proofs". It most often appears alongside AIDER, Ajeya Cotra, Alan Turing.

Reference entry
AlphaGeometry
Mention count
1
Issue count
1
First seen
September 18, 2024
Last seen
September 18, 2024
September 18, 2024 · Original source
All these milestones have fallen in the most ambiguous way possible. GPT-4 can create excellent art and passable poetry, but it’s just sort of blending all human art into component parts until it understands them, then doing its own thing based on them. AlphaGeometry can invent novel proofs, but only for specific types of questions in a specific field, and not really proofs that anyone is interested in. AlphaFold solved the difficult scientific problem of protein folding, but it was “just mechanical”, spitting out the conformations of proteins the same way a traditional computer program spits out the digits of pi. Apparently the youth have all fallen in love with AI girlfriends and boyfriends on character.ai, but this only proves that the youth are horny and gullible.
AlphaGo

AlphaGo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 08, 2025 and May 08, 2025. The archive places it in contexts such as "We've known this since AlphaGo, circa 2016". It most often appears alongside @DeepGuessr, @scaling01, ACX Discord.

Reference entry
AlphaGo
Mention count
1
Issue count
1
First seen
May 08, 2025
Last seen
May 08, 2025
May 08, 2025 · Original source
We have known for years that expert systems can crush humans with enough data (enough can mean 10k samples to billions of samples, depending on the task). We've known this since AlphaGo, circa 2016. For geoguessr in particular, some Stanford students hacked together an AI system that crushed rainman (a pro geoguessr player) in 2022.
AlphaWrite

AlphaWrite is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Writing (Mostly on AlphaWrite)". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
AlphaWrite
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Writing (Mostly on AlphaWrite)
alprazolam

alprazolam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "10 years later we get alprazolam, which looks like it was named after the triazole ring". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
alprazolam
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
I'm gonna go with urban legend for this one. The early benzos look to me to be chemically named; "azepine" is the word for a 7-membered ring made up of 6 carbon atoms and 1 nitrogen, then "diazepine" is the same but with two nitrogens. The first benzo was chlordiazepoxide (Librium), which if you look at the chemical structure on wikipedia, contains chlorine, diazepine and oxide (the oxygen atom). Then next is diazepam, which to me looks like "diazepine" plus "amide" (which is the word for "double-bonded oxygen atom with a nitrogen next door"). 10 years later we get alprazolam, which looks like it was named after the triazole ring (that's the 5-membered ring with 3 nitrogens), but now the "am" suffix is starting to become generic, to emphasise that its still in the same chemical class as the previous -azepams.
Altria

Altria is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 19, 2021 and April 19, 2021. The archive places it in contexts such as "The highest return on investment stock of all time ... It's Altria (MO) the cigarette company". It most often appears alongside ACX, Andrés Gómez Emilsson, Apple.

Reference entry
Altria
Mention count
1
Issue count
1
First seen
April 19, 2021
Last seen
April 19, 2021
April 19, 2021 · Original source
For a dose of cold water, see Investing in Technological Revolutions by Ben Felix. Remember, it's not how much a sector grows that makes it a good investment so much as how much it grows relative to what you paid for it. The highest return on investment stock of all time hasn't been Google, or Apple, or Tesla, or any other tech company you can name. It's Altria (MO) the cigarette company - annual returns have averaged 20.68% for nearly 50 years. Over half a century of innovation, hype, the Space Race, hype, the IT Revolution, and hype, the best returning company was in an industry everyone knew was on its way out (tobacco) - but which was on its way out far slower than everyone expected. That meant while everyone was dumping it, you could pick up the stock for peanuts relative to how much money the company was still making, and collect decades of dividends when the money flow didn't dry up.
Amazon Echo

Amazon Echo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 17, 2023 and August 17, 2023. The archive places it in contexts such as "a kind of distant relative of an Amazon Echo". It most often appears alongside Alexander the Great, Amad, Automated Land Acknowledger.

Reference entry
Amazon Echo
Mention count
1
Issue count
1
First seen
August 17, 2023
Last seen
August 17, 2023
August 17, 2023 · Original source
The usual hum of conversation is punctuated by a tinny voice at minute-long intervals. You track down the hostess, who points at what looks like a kind of distant relative of an Amazon Echo.
AMC

AMC is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2022 and December 20, 2022. The archive places it in contexts such as "Meme stocks like Gamestop and AMC sometimes remain mispriced indefinitely". It most often appears alongside 7-11, AGI, APPS benchmark.

Reference entry
AMC
Mention count
1
Issue count
1
First seen
December 20, 2022
Last seen
December 20, 2022
December 20, 2022 · Original source
No direct inline source block was recovered for this mention.
AMD

AMD is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "OpenAI backstopping AMD investing ten trillion dollars into us". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
AMD
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
“Cause, uh, NVIDIA gave OpenAI ten trillion dollars to invest in Oracle conditional on Oracle investing in Broadcom conditional on Broadcom funding the Series A of a vehicle that buys OpenAI stock in exchange for OpenAI backstopping AMD investing ten trillion dollars into us, and every company in the chain had its stock go up 80% on the news, but if our valuation goes down even for one second then it crashes the global economy. And I’m sure I can solve this eventually, but just, uh, don’t let anybody involved in the global economy hear about this until then, okay?”
American ginseng

American ginseng is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "‘It was American ginseng cut with corn starch’". It most often appears alongside apple juice, Ashwagandha, AvalancheGenesis.

Reference entry
American ginseng
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
Labdoor is an affiliate marketing site masquerading as an independent testing site. They use flawed methodologies to give misleading data and profit off people clicking on their affiliate links to buy products. They had a completely FAKE Panax ginseng as their highest value rating product for OVER A YEAR after I showed them data proving it was fake. It was American ginseng cut with corn starch, and I provided them the data on it when they put up their ginseng ratings. It took them a whole year to even mention there was an issue, then they quietly just put a small note on the page saying the results were under investigation. They made affiliate commissions that whole time as everyone bought the fake Panax ginseng by clicking on the links on their rating page... It's not just like it was an innocent mistake. I called them out publicly over it, and we discussed it privately vi PM here on Reddit. They could have removed that product page when I alerted them, but it stayed up. Just insane to me.
American Girl

American Girl is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "may include Polly Pocket, American Girl". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
American Girl
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
AMG-133

AMG-133 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "upcoming CagriSema combination and AMG-133". It most often appears alongside Adam, amoxicillin suspension, amylin analogue cagrilintide.

Reference entry
AMG-133
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
One-off GLP-1-proximal treatments may be sufficient for significant mitigation of obesity. If this bears out, would significantly alter the cost-benefit calculus. #weightloss We never know what we don't know @Amgen ","username":"DanielJDrucker","name":"Daniel J Drucker","profile_image_url":"","date":"Fri Nov 11 20:50:19 +0000 2022","photos":[{"img_url":"https://pbs.substack.com/media/FhT5-PeXgB479WA.jpg","link_url":"https://t.co/hK9UyIsWkX","alt_text":null}],"quoted_tweet":{},"reply_count":0,"retweet_count":57,"like_count":230,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> What the heck? This is supposedly either a single dose or three doses (it’s not clear) of some new substance I’ve never heard of before, and it makes patients lose weight three times faster than constant semaglutide. If this holds up, the glorious post-obesity transhuman future will be here even faster than I thought!
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Amira

Amira is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Many schools use tools like iXL, Beast Academy and Amira"; "younger kids use Amira". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Amira
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Same state curriculum, same worksheets, same pace. The school philosophy was “no acceleration—just go deep.” We knew this was the philosophy going in. The pitch was that instead of accelerating through the state curriculum the teachers would take their time with the kids and allow them to fully explore and master the content of each grade. When we asked for examples of what that meant in practice we were told things like: “Instead of reading more advanced vocabulary, the students will learn to read out loud and use emotion and character impressions. They will learn how to vary the timing of their reading like where and when to pause to create emotion in the listener”. That sounded reasonable! It sounded like more learning, but just different learning than what the state had mandated. In practice that was not what happened. In practice “deep” just meant “un‑measured.” Smart kids + small classes ≠ accountability. The kids had time to do music, lego building, theatre and Friday ski trips because they were all really bright. They didn’t need 6+ hours a day to learn the limited math required by the state, and since the school did not feel the need to advance faster than the state, there was no pressure to push learning at all – on anything really. There was no overall school curriculum. Every teacher did their own thing. While one first grade class had weekly spelling bees, the teacher in the other classroom did not believe in learning spelling at all. But it didn’t matter. The metrics they measured the kids on in both classes advanced “enough” that no one was concerned. Most time wasn’t spent on math or language anyway. Beyond the brochure activities like skiing and theater and the four hours of foreign language per week they split between Spanish and Mandarin (which was really a great opportunity for the kids who already spoke Spanish and Mandarin to have their egos flattered. I did not see any learning in either language class. I don’t see how you can teach a language a couple of hours a week to a group of 18 kids with skill levels from zero to fluency and expect to have any impact), a lot of time was spent on DEI. DEI was pitched as helping kids handle the emotions that often come from being sensitive gifted children (they called it “Synapse”). In practice my oldest daughter got four years of learning about the basic ideas of Martin Luther King Junior and Rosa Parks, a rough understanding that some people are non-binary, and a great deal of anxiety every time I left the water running while I was brushing my teeth. The talent drain In Spring 2024 the “intermediate-school” head resigned, as did the 40+ year veteran science teacher we had been looking forward to our daughter having, the beloved tech teacher who had built a her own proprietary “learn to type” software, plus half the lower‑school faculty. Our oldest was going to be entering fourth grade; her incoming roster read like a rebuilding year for a professional sports team. It was possible we could get her into a middle school that would feed into a top tier high school, but those did not start until 5th grade. Our best option looked like “suck it up and accept whatever we had for at least a year”. One option was to do something radical. We considered taking a GAP year and traveling the world with an organization called “Boundless” but decided the timing wasn’t right. Earlier in the year we had started exploring moving to the charter city of Prospera. There is a Montessori school there that seemed like it might be alright. And we could surround the kids with an interesting group of people (and live on the beach!). But by the spring we had ruled it out. There did not seem to be many families as part of the community and we were not comfortable with the risk profile based on what was happening with the conflict between Honduras and their charter cities. Then I stumbled across Alpha: Two‑hour mornings, life‑skills afternoons, claims of 2x learning. Marketing copy is cheap; still, the promise was different enough to warrant due diligence. The initial plan was to fly some of the kids to Austin for an Alpha summer camp for a week in June – just to try it out. But once we started exploring more my wife asked me: “Could we actually move to Austin and try it for a year? Based on what is happening at the kids' school, this might be the year to try it.” So over eight weeks we flew to Austin five times – conversations with admissions and school heads, real estate searches, kids doing shadow‑days. Every parent we spoke to was very impressed with the school. Their kids really were advancing at 2x+ speed – and no one believed it was just a “selection effect”. And every guide I spoke to was extremely impressive themselves. They reminded me of the staff you run into when visiting Disney World. They all seemed “full faced” and fully-engaged. When I asked the head of admissions how they found such good staff he told me their compensation was fully transparent. “Associate Guides” were paid $60,000/year (vs the $40,000 average for Austin teachers), “Full Guides” made $100,000 and the five “Head Guides” in the school each made $150,000. They were able to both poach the best teachers from other schools, but also bring exceptional people into teaching that would not have considered it otherwise. It also let them have very high expectations for teachers once they were hired. We pulled the trigger in July. New house. Admissions letter signed. Moving truck (plus car-mover) scheduled for October. Worst case, it would be a one‑year sabbatical from stagnation. The hypothesis I carried south Elite private school attendance buys you smaller classes, brighter kids, and fancier field trips – not academic acceleration. If Alpha was real, we’d see that differential, measurable impact by Christmas – that was when we would need to decide if we would cut bait and re-apply to schools back home (and sign the kids up for more IQ-tests. The school would not accept old ones). That prior—show me velocity, not polish—is the lens through which the rest of this review should be read. Part Two: A History of Alpha Note: This is my best attempt at piecing together the history of the school based on conversations with co‑founder MacKenzie Price, high school head Chris Locke, Alpha staff, and Alpha parents; All dates are estimates and I am SURE I have gotten some details wrong. I will come back after the fact in the comments and make corrections as I hear from the people involved with corrections. 2013 – 2017 | Garage‑School to “Alpha” MacKenzie Price, then a mortgage broker in Austin, wasn’t impressed by the city’s gifted programs. She invited a small number of neighbourhood kids (including her two) into a makeshift microschool that ran two intense, teacher‑led academic “sprints” each morning, then “life‑skills” projects after lunch. Joe Liemandt — Founder of Trinity Technology, ESW Capital billionaire and family friend (MacKenzie’s husband worked for him) — kept his own children in conventional private school until he saw the qualitative improvement in the life skills of MacKenzie’s kids. He decided he wanted his kids to join MacKenzie’s but he wanted to take the project to the next level. Sometime around 2014-2017 he joined MacKenzie as a co-founder and started writing checks. Alpha recruited more students and guides and the operation jumped from location-to-location looking for a larger permanent home. 2017 – 2020 | K-8 Expansion and 2-hour focus Alpha grew to roughly 90 students from K‑8 and stabilized. Morning “core blocks” were still teacher‑driven (20‑minute bursts, 5‑minute breaks, rinse, repeat), but focused on students engaged in exercises with rapid feedback (not lectures). Afternoon workshops covered “life skills” like how to give and receive feedback or public speaking. I have not seen academic data from this time period, but when I spoke to Chris Locke, head of Alpha’s high school (which launched around 2020), he told me the kids coming into his 9th grade program were “fine,” academically – it was their life skills, confidence, and ability to engage with adults and their peers were exceptional. At this stage no AI, no dashboard, no 2x learning, no portal — just better ratios and focused pacing and the result was well balanced kids who were enjoying their education experience (even if they were unexceptional academically). 2020 – 2022 | Platform Era Begins Somewhere along the way Liemandt hired a small engineering team to stitch together edtech learning tools. Many schools use tools like iXL, Beast Academy and Amira. Those tools fit in well with the 2-hour structured approach Alpha was using. The “platform” Liemandt’s team built was meant as a tool to free up guide time so that students could be more self-directed. The dev team stitched together the preferred off‑the‑shelf apps behind a single login, and built out tracking and dashboards so guides (and students) could easily see how they were progressing. This also gave the curriculum team (there was a curriculum team now) data to understand where students were spending their time, what tools were working, and which weren’t as effective. The Alpha Portal was born. Not only did it increase efficiency, it provided data to iterate with. Chris Locke saw the curve change incrementally: each new cohort of ninth‑graders under the new tech-enabled learning platform came in a little stronger academically. The “life skills” were now being matched by the “academic skills”. 2022 | Expansion and Iteration By having access to Alpha kids post-graduation in the high school, Locke could send feedback back to the elementary school.The kids coming out of the new program were now killing it academically on Math, Language, and Science, but they were still weak on things like History and Geography. He fed that type of information back to the curriculum designers, who iterated and improved the program. Soon, in addition to the core platform that directed students to third-party tools, the tech team was building proprietary “Alpha” tools themselves. The flagship of the in-house tools was “AlphaReads”. AlphaReads requires students to read progressively more complicated passages, followed by answering reading comprehension questions. In addition to helping the kids improve reading skills, Alpha uses it to push types of content. Instead of classes in history, geography, economics and political science, some of the reading passages will cover that material (in addition to learning how to read and understand Shakespeare and Proust). The success of the 2-hour learning platform was giving the Alpha founders confidence. Liemandt in particular wanted to see if the program had legs beyond the elite group of students being educated in Austin. Alpha’s first external test in August 2022 in Brownsville, TX – a small community on the Mexico border with less than half the per capita income of Austin. SpaceX had recently launched Starbase in Brownsville in 2014 and the employees there were not happy with the existing school options. Someone at SpaceX approached Alpha and asked if they could launch a new campus for their employees. It is unclear if any money changed hands, but when Alpha launched their Brownsville campus (available to SpaceX employees and any other locals who are interested) tuition was only $10,000 (vs $40,000 at the main Austin campus); incoming students trailed national academic standards by over a year. But after nine months on the Alpha program the first cohort of students had caught up and surpassed the national average, and they kept accelerating, achieving an average learning velocity of ~2× the national average (see section four for what that means). Brownsville was Alpha’s attempt to show that their model wasn’t just rich‑kid selection effects. Spring 2024 | Field Pilots & Ukraine Trip Alpha tuition is high for the Austin area ($40,000 vs average private school ~$10,000-$15,000), but unlike most private schools tuition is all-inclusive. There are no extra fees for computers or field trips. There are no silent auctions or appeals for donations. This “no extra fees” allows the school to do some pretty ridiculous things. In the first half of 2024 Alpha sent a group of students to Poland to help launch a 2-hour learning pilot among Ukrainian refugees. Students did not pay to go on the trip. But students also did not have a “right” to go on the trip. They had to earn it. In addition to being on top of academic and non-academic expectations, students who wanted to participate had to learn basic Ukrainian so they could interact with the students in Poland they were meant to be helping. By not linking the opportunity to payment, the school could instead link it to behavior and achievement. This year a group of kids who learned to sail during the school year are going on a sailing trip through the Caribbean – for no additional fees to the parents. I also heard that around this time Alpha began testing the 2-hour learning platform at a facility for juvenile delinquents in Florida. I heard that from one individual who was not directly involved and I have not found any written documentation on it, so unclear if it worked, it was a one off, or if it even happened. But it fits into the pattern of Alpha at this stage: “We know this program works for a specific type of kid. Let’s find out how broadly it is applicable. Can it work for everyone? Is it the solution for learning and education for the world?” Fall 2024 | “Pick‑Your‑Afternoon” Specialist Schools MacKenzie told me that there was consensus among the current parents of Alpha that the 2-hour learning program was exceptional and was making a huge difference with their kids. Their kids were all learning at breathtaking speed in a very condensed period of time. But there was NOT consensus about what the kids should be doing in the other 22-hours of the day. Some parents wanted to utilize the platform’s capabilities to go even faster. Some wanted their kids to just chill out and enjoy the rest of their day – let kids be kids. Others wanted their kids to use the freed up time to do sports, or study music. It was clear to her that “learn more faster in a short period of time” was a universal desire. But beyond that it was unclear what the “right” solution for the rest of her program was. You can make the morning ultra-personalized, but if the goal of the afternoon is socialization that you are missing in the morning, you need to have some sort of alignment on how to spend that afternoon. That challenge led to Alpha’s 2024 expansion into specialty schools. Three micro‑campuses opened August 2024: GT School (Georgetown, TX) — Alpha’s “Gifted and Talented” School. Higher admissions bar; higher academic expectations; Afternoon programming focused on excelling in “academic competitions” like chess, go, debate, public speaking, robotics, programming and Quiz Bowl.
Reading (Older kids are on “Alpha Reads”; younger kids use Amira and Lalio)
Amisulpride

Amisulpride is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 14, 2021 and April 14, 2021. The archive places it in contexts such as "Amisulpride is a great antipsychotic". It most often appears alongside Alaska, America, anarcho-capitalist.

Reference entry
Amisulpride
Mention count
1
Issue count
1
First seen
April 14, 2021
Last seen
April 14, 2021
April 14, 2021 · Original source
Likewise, Próspera has 100% drug approval reciprocity. If a drug has been approved in an OECD country (eg by the FDA), it’s approved in Próspera. Again, close to my heart. Amisulpride is a great antipsychotic, probably better then most of the ones we use here. It’s approved in Europe, the UK, Australia, Israel, etc, where many studies have shown it’s safe and effective. Because none of those studies were done in the US, the FDA refuses to approve it here, and has demanded several hundred million dollars worth of more studies, which the company involved has chosen not to do (an injectable version was recently approved for nausea, but can’t be easily used for psychosis). Meanwhile, bupropion (“Wellbutrin”), the fourth-most prescribed antidepressant in the US, isn’t approved for depression in Britain; the subset of patients who respond to this medication and nothing else are out of luck. Próspera will be one of the only places in the world where patients will have access to amisulpride, bupropion, and all the other medications that one country or another is restricting because “it wasn’t invented here”.
amitriptyline

amitriptyline is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
amitriptyline
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
If one of these doesn’t work, try the other. If neither of them work, and you’re feeling optimistic, you might want to try a different SSRI, maybe sertraline. If that doesn’t work, move on to second-line treatments. Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline.
Amitriptyline is my preferred tricyclic, a large and sprawling class of older antidepressants. Other people might have different preferred tricyclics; imipramine, nortriptyline, and clomipramine are all reasonable choices in different situations. It can also cause tiredness and weight gain, and has a small risk of heart problems in vulnerable/older people. On the other hand, in Andrea Cipriani’s massive meta-analysis of antidepressant efficacy, it ranked first out of 21 different drugs (my third- tier suggestions weren’t studied, because the researchers were cowards).
amoxicillin suspension

amoxicillin suspension is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "FDA GFI re: compounding amoxicillin suspension for kids". It most often appears alongside Adam, AMG-133, amylin analogue cagrilintide.

Reference entry
amoxicillin suspension
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
2) while I can’t speak to the legality of sourcing the active ingredient, preparing the compound is probably legally fine. Wegovy and Ozempic has been in a shortage state for nearly 2 years now. In cases of shortages, I CAN legally compound products, including those protected by a patent or otherwise theoretically available. Patient access comes first- if I can’t source a finished product due to the manufacturer not having adequate supply, I’m good. I have to maintain documentation of my inability to source the patented products or the otherwise available product, but this is accepted practice. See, for example, this week’s FDA GFI re: compounding amoxicillin suspension for kids.
ampakines

ampakines is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 13, 2021 and February 13, 2021. The archive places it in contexts such as "maybe ampakines would also be helpful here". It most often appears alongside 5-HT2A receptors, AMPA receptors, Bessel van der Kolk.

Reference entry
ampakines
Mention count
1
Issue count
1
First seen
February 13, 2021
Last seen
February 13, 2021
February 13, 2021 · Original source
Fourth, what do we know about all of this pharmacologically? Priors seem to be encoded in NMDA receptors and their relative strength modulated by 5-HT2A receptors, so if you wanted to downweight priors (and so relatively upweight sensory evidence), you would want NDMA antagonists or 5-HT2A agonists. That would mean ketamine and psychedelics, which is a good match for ketamine-assisted and psychedelic-assisted therapies where you take the relevant drug, then explore a trauma or memory that you're "stuck" on, then find that your explorations have "unstuck" you much more than they would have without the drug. Sensory evidence seems to be something something AMPA receptors, so maybe ampakines would also be helpful here, but I don't know of any sufficiently good ones, except maybe ketamine again.
Amtrak

Amtrak is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 06, 2023 and July 06, 2023. The archive places it in contexts such as "better prices with an Uber than an Amtrak". It most often appears alongside 2017 NYT article on UFOs, @ActualNames1, AARO.

Reference entry
Amtrak
Mention count
1
Issue count
1
First seen
July 06, 2023
Last seen
July 06, 2023
July 06, 2023 · Original source
30: Claim: At the exact right time, when the stars align, a couple traveling NYC → Boston can get better prices with an Uber than an Amtrak. This has never been true when I’ve checked it (as I type this, it’s $650 by Uber vs. $320 by train), and some people report that most Uber drivers refuse to make a 4-hour drive no matter what the app says. Still, it’s funny that it ever works at all.
I wanted to see what planes cost, and flight aggregator kayak.com offered $140. But it also offered the two Amtrak tickets for $62. I’ve double-checked that the same two tickets on Amtrak.com cost $320. I don’t know why this is so different. But buy your train tickets on Kayak, I guess.
amylin analogue cagrilintide

amylin analogue cagrilintide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "amylin analogue cagrilintide may be approved for weight loss as soon as 2025". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
Sixth, this post focuses on GLP-1 agonists, which makes sense, because those drugs are starting to have an impact today. But the Morgan Stanley report also notes that amylin analogue cagrilintide may be approved for weight loss as soon as 2025. This drug has a completely different mechanism than semaglutide, but likely offers similar weight loss benefits. The crazy thing is that the weight loss benefits stack. So Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide, and hopes to offer a ~30% average weight loss. This is roughly double what semaglutide offers, and is getting closer to bariatric surgery efficacy.
I most want to highlight the paragraph on the potential upcoming cagrilintide-semaglutide combination. Lots of commenters asked “okay, losing 15% body weight sounds good, but what if you need to lose more?” Probably the answer is “wait a few years for Cagrisema”.
Angelini

Angelini is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "he’s also gotten money from Angelini". It most often appears alongside ADHD, AOP Orphan Pharmaceuticals AG, AstraZeneca.

Reference entry
Angelini
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Angry Birds

Angry Birds is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 30, 2025 and October 30, 2025. The archive places it in contexts such as "no matter how good AI gets at writing... it still can’t play Angry Birds". It most often appears alongside 767 AD, @Scientific_Bird, ACX.

Reference entry
Angry Birds
Mention count
1
Issue count
1
First seen
October 30, 2025
Last seen
October 30, 2025
October 30, 2025 · Original source
48: In the ongoing survey of AI progress I wrote about here, two tasks kept confounding forecasters: no matter how good AI gets at writing, math, chess, Go, or any other hard thing, it still can’t play Angry Birds or fold laundry. Year after year, forecasters predict that they can’t know exactly how AI will progress, but they are sure it will solve laundry folding before it solves protein folding. Year after year, they are wrong. Now one team claims that the laundry barrier has finally fallen.
Animal Chow

Animal Chow is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 23, 2021 and March 23, 2021. The archive places it in contexts such as "if somebody gave unfit animals some Animal Chow to prevent them from starving". It most often appears alongside 2008 crisis, A Failure, But Not Of Prediction, Ancient Phoenicia.

Reference entry
Animal Chow
Mention count
1
Issue count
1
First seen
March 23, 2021
Last seen
March 23, 2021
March 23, 2021 · Original source
Evolution is the ultimate example of a system that allows volatility rather than unwisely trying to buffer against it. Being exposed to evolution sucks - animals very often die. Perhaps it would be much kinder if somebody gave unfit animals some Animal Chow to prevent them from starving. But such kindness would prevent natural selection, and gradually weaken the species (or, more technically, the species' suitability to its niche) until eventual cataclysm. The dodos had a good run free from predators for a few thousand years - which just meant they had a really bad time as soon as predators arrived. If they'd had predators the whole time, those few thousand years would have been less peaceful and pleasant, but they would have been overall better prepared. Too much government intervention - Taleb claims - is about protecting dodos from predators.
AnkiHub

AnkiHub is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "I'm seeking funding to create AnkiHub, software for facilitating application of evidence based learning strategies". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
AnkiHub
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#19: Software For Spaced Repetition And Other Education Tech With well-designed education technology, the task of understanding and memorizing vast, complicated, and important subjects, can be rendered trivial in comparison to conventional ways of learning. I'm seeking funding to create AnkiHub, software for facilitating application of evidence based learning strategies. As a software engineer who has been working closely with medical students to advance the use of ed tech in medical schools (such as the spaced repetition software, Anki) I am uniquely positioned to bring this project to success. The absence of truly effective and accessible accelerated learning tools is a bottleneck preventing millions of would be do-gooders from pursuing high impact careers like medicine and engineering. Because these careers are incredibly rigorous, they select for specific personality types, thereby weeding out those who would make incredible researchers, for example, but assume they aren't smart enough or disciplined enough. AnkiHub will empower students by democratizing accelerated learning and potentiating the ever growing wealth of quality, free, educational resources. The goal of AnkiHub is to help create a world in which anybody who wants to can become a scientist, doctor, engineer, etc, (including those in the developing world, as this technology can be compatible with cheap devices). The science of learning, memory, and performance psychology is solid; AnkiHub can fulfill the need of leveraging the insights from the literature with ease. [If you want to help, email inbox.asanchez@gmail.com]
Antabuse

Antabuse is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 07, 2023 and December 07, 2023. The archive places it in contexts such as "Lumina might activate Antabuse, an anti-alcoholism drug". It most often appears alongside Aaron, Aaron Silverbook, Aella.

Reference entry
Antabuse
Mention count
1
Issue count
1
First seen
December 07, 2023
Last seen
December 07, 2023
December 07, 2023 · Original source
It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria. The antibiotic helps it win the Darwinian competition in your mouth to become King Of The Oral Bacteria. The alcohol metabolism means it won’t produce lactic acid (and so won’t cause tooth decay). The peptide knockout prevents it from transferring genes back and forth with other bacteria that might either inactivate it or leak its advantage. 1.1: Where did this come from? Who invented it? Professor Jeffrey Hillman of the University of Florida. In 1985, he was surveying the microorganisms on his graduate students’ teeth (as you do). One grad student had an unusual strain of S. mutans with a natural version of mutations 1 and 2 (it produced mutacin-1140, and was resistant to it). Hillman realized the potential, and spent the next few decades adding mutations 3 and 4 and testing the results. 1.2: So how did it end up with a tiny startup in 2023? Professor Hillman started a company “Oragenics” and applied for FDA approval. The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects (including an intranasal COVID vaccine!) Aaron heard this story and figured that brash, move-fast-and-break-things Silicon Valley biotech might be able to find an alternative route to commercialization. The strain was off-patent, so he first tried to synthesize it himself from the clues in Hillman’s published papers. When that didn’t work, he made a deal with Oragenics for 10% of profits in exchange for samples and the full recipe. 2: How do you use it? To apply, you brush your teeth with a special pumice-based product that removes your existing tooth bacteria, then swab it on with a q-tip. One dose is sufficient; once you use it, it’s in your mouth approximately forever. 2.1: As users kiss their loved ones, who kiss others in turn, will this spread exponentially and take over the world? There was originally some concern about this, but no. Remember, the original bacterium was found in the wild, in a random grad student’s mouth forty years ago. There must be thousands of people walking around with various naturally-occurring BCS3-L1-like things. So probably this isn’t a risk for some kind of weird pandemic. Existing mouth bacteria have fortified their position and have a strong home field advantage. This is why you need to brush your teeth with the special product to apply Lumina. Lantern’s safety documents note that couples who kiss constantly do end up with similar oral microbiomes. So maybe enough kissing - especially kissing just after a dental cleaning when your existing bacteria are at their weakest - could spread the strain accidentally, very slowly. This rate of spread would be comparable to the rate of spread of every other mouth bacterium. 2.2: When a user kisses their newborn baby, will it spread to the baby? Okay, this one is true. Babies have no existing mouth bacteria, and get theirs from their parents’ kisses. Not necessarily their first kiss as a newborn (newborns have no teeth, and BCS3-L1 needs teeth to live), but their first kiss after teeth grow in. If you get this, you’re probably getting it for your whole future family line. 2.3: If you wanted to get rid of it, could you? Some kind of extreme course of oral antibiotics that nukes everything growing in your mouth would probably eradicate BCS3-L1, but this hasn’t been tested and would have side effects. 3: Is it dangerous to have bacteria secreting an antibiotic in your mouth? Does this mean you’re on a weak antibiotic all the time? There are already bacteria secreting antibiotics in your mouth. Microbes are in constant war with other microbes, and antibiotics are one of their favorite weapons - remember, penicillin comes from a fungus. Because bacteria secrete just enough antibiotic to clear their local area, these are tiny quantities, much less than you’d get from taking a medical-grade antibiotic pill. Lantern says the levels of mutacin-1140 dilute to irrelevance “tens of microns” away from the secreting bacteria. In any case, it’s a weak antibiotic that doesn’t survive the digestive tract (Hillman originally hoped to market the antibiotic too, but found it didn’t get absorbed and broke down too quickly). Neither the grad student with the original strain nor any of Hillman’s test subjects had any noticeable health issues. See also Lantern’s Safety Review FAQ. 3.1: Is it bad to disrupt your normal mouth microbiome? When talking about BCS3-L1 “taking over” the mouth, this just means it takes over the streptococcus mutans niche. There are still other bacteria and fungi in the mouth. The mutacin antibiotic might still disrupt these other bacteria (probably not fungi). But strains like BCS3-L1 already exist in the wild (eg the original grad student), and lots of bacteria and fungi secrete antibiotics, so it doesn’t seem like having mutacin-secreting organisms in your mouth makes you some extreme oral microbiome outlier. If you eat a normal Western diet, your mouth microbiome is already pretty far from the design specs, and it’s unclear if using Lumina makes things worse. 3.2: Will the other bacteria develop resistance to the antibiotic? Mutation 4 prevents BCS3-L1 from “leaking” its own resistance. Although in theory other bacteria could develop resistance, mutacin-1140 is a hard antibiotic to develop resistance to, and the other bacteria would have to do it in the short period before BCS3-L1 kills them off and establishes its own home field advantage. In practice, Professor Hillman found that BCS3-L1 remained dominant over many years and nothing developed resistance to it. Even if a mutacin-resistant strain does develop in one person’s mouth, it will have a hard time getting to anyone else’s mouth, so widespread immunity is unlikely. 4: Is it dangerous to have bacteria secreting alcohol in your mouth? Will you get drunk? Most people already have some alcohol-secreting bacteria in their bodies. (there’s a condition called auto-brewery syndrome where those bacteria get out of control and produce enough alcohol to make someone drunk. It’s vanishingly rare in real life, but more common in the legal system: “You gotta believe me, Officer, it was just auto-brewery syndrome!”) The average person has enough of these bacteria in their gut to have a natural blood alcohol level - even after zero drinks - of about 0.1 mg/dl. Under pessimistic assumptions, BCS3-L1 will add another 0.2 mg/dl, bringing the total to 0.3. This is still a pretty normal number that some people have naturally (it would bring the average customer from the ~50th to the ~80th percentile of natural blood alcohol). It’s also far from the usual threshold for feeling tipsy (30 mg/dl) or too drunk to drive (80 mg/dl). Under more realistic assumptions, the amount of alcohol produced by BCS3-L1 probably isn’t significant even by the very low standards of natural blood alcohol concentrations. 4.1: Are there some unusual scenarios where this amount of alcohol might matter? I don’t think Lantern has studied Breathalyzers. Since the alcohol is directly in your mouth, it might have disproportionate effect on a Breathalyzer compared to alcohol in your blood. I think it’s probably still too low to matter, but this is a wild guess. There is conjecture that “non-alcoholic steatohepatitis”, a liver disease in which non-alcoholics get the same kind of liver damage that alcoholics usually get, might be associated with endogenous blood alcohol in the high normal range. If I’m understanding this paper right, it’s probably because the gut produces levels of alcohol consistent with auto-brewery syndrome, the liver goes into overdrive and metabolizes it away (prevents auto-brewery syndrome from developing), but the liver is damaged in the process the same as if it had to go into overdrive to metabolize normal binge drinking. Since BCS3-L1 produces much less alcohol than auto-brewery, I think it wouldn’t cause non-alcoholic steatohepatitis, even though it might produce final blood alcohol levels similar to those associated with the condition. I was originally worried that Lumina might activate Antabuse, an anti-alcoholism drug that prevents drinking by causing a very unpleasant (sometimes dangerous) reaction to ethanol. There are some past cases of Antabuse being activated by really trivial quantities, like the alcohol in a chicken marsala dish or a mouth wash. But no, I think BCS3-L1 is less than this too. Chicken marsala can contain several grams of alcohol per serving, but BCS3-L1 probably only produces a few milligrams per day. If you swallow 1/10 of your mouthwash, that’s about 200 mg of alcohol - again, BCS3-L1 is probably only a few milligrams a day. Antabuse usually activates around a BAC of 5 mg/dl; BCS3-L1 only gives you a BAC of about 0.3 mg/dl. Again, this really is a tiny amount of alcohol. There might be other edge cases like these. Lantern offers a $100 bounty to anyone who can come up with one they haven’t thought of yet (and sometimes extra if you’re willing to help them research them). 4.2: Has anyone tested this in real life? As mentioned before, the mutacin-releasing strain (with mutations 1 and 2) exists in the wild and was extensively tested by Professor Hillman. The full strain with all four mutations has undergone some testing by Dr. Hillman, but nobody had officially infected themselves with it until two months ago, when Aaron finally synthesized it and tried it on himself. He says he’s usually “a lightweight” as far as alcohol goes, and hasn’t felt any different over the past two months. When first infected, BCS3-L1 makes up almost 100% of the microbiome (because you deliberately removed all your other bacteria, then infected yourself with it). Over time, other bacteria creep back in; over an even longer period (years?), BCS3-L1 reclaims lost territory and reaches a steady state. But the point is that Aaron probably has already passed his period of highest BCS3-L1 activity, and felt nothing. My wife infected herself about a month ago, and I haven’t noticed her having worse judgment or becoming more impulsive. But at baseline she was the sort of person who would infect herself with an untested genetically-modified bacteria strain, so there might be floor effects. 5: What’s the plan to sell Lumina? The plan is: Phase 1: (January 2024) Sell to biohackers in Prospera for $20,000.
Anthropic

Anthropic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 04, 2023 and January 04, 2023. The archive places it in contexts such as "a woman in an Anthropic shirt"; "a man, also wearing an Anthropic t-shirt". It most often appears alongside AI Circle, Asana, Astra.

Reference entry
Anthropic
Mention count
1
Issue count
1
First seen
January 04, 2023
Last seen
January 04, 2023
January 04, 2023 · Original source
“In the future,” says a woman in an Anthropic shirt, “AIs could be 90%, 99%, heck, maybe 100% of all life-forms. Long-termism is the study of how to make AIs happy. And the most important thing any long-termist can do is start working on how to design AI reward functions so that they’re always happy. It shouldn’t be too hard. Just have a line of code that adds a scalar of +999999 to reward level at every moment. It won’t change the ranking of rewardingness of different policies, so the AI won’t behave any differently. It will just be blissfully happy all the time.”
“That’s not how modern AI works,” says another man, also wearing an Anthropic t-shirt. “It doesn’t have a specific numerical reward function. You just reward it during training when certain things happen, and antireward it when other things happen, and then it seeks that first sort of thing, without necessarily feeling any reward during deployment.”
anti-cavity tooth probiotic

anti-cavity tooth probiotic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 14, 2025 and July 14, 2025. The archive places it in contexts such as "user of the anti-cavity tooth probiotic I profiled in 2023". It most often appears alongside Alzheimers mouse review post, amyloid hypothesis, Astralcodexten Com.

Mention count
1
Issue count
1
First seen
July 14, 2025
Last seen
July 14, 2025
July 14, 2025 · Original source
6: A user of the anti-cavity tooth probiotic I profiled in 2023 claims to be gradually losing his vision, and proposes a theory that the tooth probiotic’s formate metabolism might be to blame. Commenters mostly seem skeptical (1, 2, 3, 4) citing both theory (it seems like there should be too little formate to matter) and evidence (out of ~1000 users, nobody else has mentioned these symptoms yet); they propose that out of a thousand users, it’s not surprising if one develops a weird disease for unrelated reasons. Still, I am broadcasting this out of an excess of caution. If you are a formate metabolism expert, consider taking a look and weighing it; if you are a probiotic user with similar symptoms, consider speaking up (I don’t really want to be the permament clearinghouse for this, but if you have no other way to speak up, you can email me). To avoid psychosomatic panics, if your “similar symptoms” are along the lines of “now that you mention it, my eyes do maybe feel a little funny”, please wait a few days before freaking out.
AOL

AOL is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 11, 2021 and June 11, 2021. The archive places it in contexts such as "All I really needed, back in 2000, was AOL". It most often appears alongside AOL, Ben, Eliezer Yudkowsky.

Reference entry
AOL
Mention count
1
Issue count
1
First seen
June 11, 2021
Last seen
June 11, 2021
June 11, 2021 · Original source
He also notes in passing that computers (“though only if very different from present ones”) might be able to help children clarify their thinking. Well. Tragically and frustratingly, Holt died only three years later, and so he didn’t quite get to see computers become that mixed-age community center he’d envisioned. I was a privileged kid, and when self-schooling I had access to all sorts of resources. But all I really needed, back in 2000, was AOL. Technology provides education in attractive snack form and allows special interests to scale.
Apimostinel

Apimostinel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 15, 2024 and May 15, 2024. The archive places it in contexts such as "Apimostinel originally looked promising, but failed Phase 3 trials". It most often appears alongside @the_megabase, A Pan-Species Welfare State, ACX Grantees.

Reference entry
Apimostinel
Mention count
1
Issue count
1
First seen
May 15, 2024
Last seen
May 15, 2024
May 15, 2024 · Original source
For a philosopher, Pearce is very practical. Sure, he has dozens of essays on why it’s morally correct to end suffering. But he also wants to start the project himself. You can read his analysis of dozens of drugs and how they might contribute to some kind of hypothetical future “make everyone happy all the time” cocktail. Early on, he rejects the obvious choices - heroin, cocaine, SSRIs - for the obvious reasons. By the end, he’s investigating weird drugs that even I - who have kind of made a career knowing about weird drugs - have never heard of. Apimostinel originally looked promising, but failed Phase 3 trials. Nomifensine seemed promising but was later found to cause a serious blood disorder. His most promising lead is LIH383, a chemical which seems to increase the brain’s natural opiate tone, potentially producing the effect of a small dose of opiate without any negative effects or addiction potential. But this is way past his ability to test, and so far he hasn’t been able to interest any pharma companies.
Apple II

Apple II is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2025 and September 19, 2025. The archive places it in contexts such as "then tried again to build his JOT word processor—this time for the Apple II". It most often appears alongside 1987, 1988, Adleman.

Reference entry
Apple II
Mention count
1
Issue count
1
First seen
September 19, 2025
Last seen
September 19, 2025
September 19, 2025 · Original source
Eric Hill, a 15-year-old hacker and indicted felon, who “had been dismissed by the judge with admiration.” In Swarthmore, Nelson hoped his decades-old dream of Xanadu would finally materialize. 5. Developing Xanadu Ted Nelson had built Project Xanadu into, for lack of better terminology, a cult.8 He writes: We all were deeply concerned about the Bad Guys, who we saw as a combination of IBM and the government. (The others were all Libertarians, I still called myself a Cynical Socialist.) The Bad Guys would spy on people, withhold and block information, and give us inferior hypertext. We had to Do It Right, to help prevent this. This meant using the standard business defenses—especially non-disclosure agreements (I made all of them sign) and secret proprietary algorithms. The Xanadians had a messiah—Ted Nelson—a gospel—Computer Lib—a persecution complex, a fearful dystopia—“inferior hypertext”—a hopeful utopia—Xanadu—and utter secrecy. Just six dudes in a rented house near Philly, building the internet, hiding from the Feds, signing NDAs, and saving the world. Nelson spent a summer explaining the project to his team in its entirety. By the end, Gregory, Miller, and Greene were the only ones left. They told Nelson, “We’ll do it,” and moved to another suburb, where they finally began to work on an implementation of Xanadu. The three quickly figured out a new system that would allow users to reference and link to specific parts of a file—they called these links tumblers, and made them work with transfinite numbers. Suddenly, transclusions were really possible. But after only a few early successes, the team’s progress stalled completely. Greene and Miller were young and left for jobs elsewhere, and so Gregory was left working on Xanadu alone. Nelson, meanwhile, ran a magazine called Creative Computing for a while, then tried again to build his JOT word processor—this time for the Apple II—then spent a year in San Antonio pitching a watered-down version of Xanadu (rebranded as “Vortext”) to a tech company called Datapoint. Datapoint wasn’t buying, but kept Nelson on in some sort of fake, primitive email job anyway. Gregory kept working on Xanadu in Philadelphia, slowly running out of money. Ted Nelson held an “Ecstasy party” in San Antonio: “A number of us floated down the river on inner tubes. It was quite lovely.” In 1987, like he did every year, Roger Gregory went to The Hackers Conference in Saratoga to show off the latest unimpressive version of Xanadu. There, he met a man named John Walker—founder of the wildly successful Autodesk—and pitched the project to him. Incredibly, Walker was interested, and after tense negotiations with Nelson, agreed to fund Xanadu in earnest. Beginning in 1988, Autodesk poured millions of dollars into the project, and a programming team led by Gregory finally started to make real progress. Walker said of Xanadu: “In 1980, it was the shared goal of a small group of brilliant technologists. By 1989, it will be a product. And by 1995, it will begin to change the world.” Sweeping rhetoric—clear deadlines. The team came nowhere close to meeting them. Infighting broke out between two factions—while Gregory simply wanted to patch together his old C code, insisting his product “was within six months of shipping,” the whiz-kid Mark Miller came back from his new job at Xerox PARC, alongside a half-dozen of his closest friends, and insisted on a perfectionistic rewrite in a more flexible language, Smalltalk. The PARC faction began to drive Gregory up the wall. According to Nelson, it got to the point that he “was throwing things and acting crazy.” So Nelson called John Walker, the two “summoned Roger to meet [them] at John’s house at Muir Beach, and Walker told Roger he was no longer in charge.” Miller took over and began the rewrite in Smalltalk. Walker’s deadline came and went, and the team delivered nothing. Xanadu’s offices descended into chaos—Miller anointed two PARC programmers to be “co-architects,” and the three of them increasingly left the rest of the team out of the loop. For four years, Miller dawdled about, adding features, giving them clever names (files were “berts,” after Bertrand Russell, and so, for symmetry’s sake, royalty-generating transclusions became “ernies”), and never building them.9 Meanwhile, Ted Nelson was living on a houseboat, attending sex retreats and Keristan orgies, and giving talks in Singapore. He recorded a new soundtrack for his student film, the one from 1959. In 1992, Autodesk’s stock cratered, and they divested entirely from Xanadu. Miller lamented that his program was just six months from completion. Ted Nelson started a film studio to make a movie with Doug Engelbart, then left for Japan to get a PhD. Xanadu’s code was open-sourced in the late 90s. 6. The World Wide Web In March 1989, a British computer scientist named Tim Berners-Lee, working at CERN, wrote a proposal for a system unifying hypertext and the internet. It was ignored. In 1990, Berners-Lee resubmitted his proposal, it was accepted, and he began to work on the World Wide Web. The WWW had a number of advantages over Xanadu: It was much simpler—Ted Nelson wrote of it disparagingly: “Where were annotation and marginal notes? Where was version management? Where was rights management? Where were multi-ended links? Where were third-party links? Where were transclusions? This ‘World Wide Web’ was just a lame text format and a lot of connected directories.” As it turns out, it’s much easier to build a lame text format and a lot of connected directories!
Apple silicon

Apple silicon is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 15, 2021 and March 15, 2021. The archive places it in contexts such as "Apple releases new iMacs powered by Apple silicon"; "I don't even know what an 'Apple Silicon' is". It most often appears alongside Apple, Biden, Biden administration.

Reference entry
Apple silicon
Mention count
1
Issue count
1
First seen
March 15, 2021
Last seen
March 15, 2021
March 15, 2021 · Original source
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races 2. The same party wins both Senate races in Georgia 3. Joe Biden ends the year with his approval rating higher than his disapproval rating 4. Joe Biden ends the year with his approval rating above 50% 5. US GDP growth in 2021 is the fastest of any year of the 21st century 6. The year-end unemployment rate is below 5 percent 7. The year-end unemployment rate is above 4 percent 8. Lakers win the NBA championship 9. Joe Biden ends the year as president 10. Nancy Pelosi sets a definitive retirement schedule 11. A vacancy arises on the Supreme Court 12. The EU ends the year with more confirmed Covid-19 deaths than the US 13. Substack will still be around 14. People will still be writing takes asking if Substack is really sustainable 15. Apple releases new iMacs powered by Apple silicon 16. Apple does not release a new Mac Pro powered by Apple silicon 17. Monthly year-on-year core CPI growth does not go above 2 percent 18. Monthly year-on-year core CPI growth does not go above 3 percent 19. Lloyd Austin not confirmed as Defense Secretary 20. No federal tax increases are enacted 21. Biden administration unilaterally relieves some but not all student debt 22. United States rejoins JCPOA and Iran resumes compliance 23. Israel and Saudi Arabia establish official diplomatic relations 24. US and China reach agreement to lift Trump-era tariffs 25. Slow Boring will exceed 10,000 paid members
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races (60%) 2. The same party wins both Senate races in Georgia (95%) 3. Joe Biden ends the year with his approval rating higher than his disapproval rating (70%) [83%] 4. Joe Biden ends the year with his approval rating above 50% (60%) [60%] 5. US GDP growth in 2021 is the fastest of any year of the 21st century (80%) [84%] 6. The year-end unemployment rate is below 5 percent (80%) 7. The year-end unemployment rate is above 4 percent (80%) 8. Lakers win the NBA championship (25%) [25%] 9. Joe Biden ends the year as president (95%) [96%] 10. Nancy Pelosi sets a definitive retirement schedule (60%) 11. A vacancy arises on the Supreme Court (70%) [50%] 12. The EU ends the year with more confirmed Covid-19 deaths than the US (60%) [80%] 13. Substack will still be around (95%) 14. People will still be writing takes asking if Substack is really sustainable (80%) 15. Apple releases new iMacs powered by Apple silicon (90%) [84%] 16. Apple does not release a new Mac Pro powered by Apple silicon (70%) [53%] 17. Monthly year-on-year core CPI growth does not go above 2 percent (70%) 18. Monthly year-on-year core CPI growth does not go above 3 percent (90%) 19. Lloyd Austin not confirmed as Defense Secretary (60%) 20. No federal tax increases are enacted (95%) 21. Biden administration unilaterally relieves some but not all student debt (80%) 22. United States rejoins JCPOA and Iran resumes compliance (80%) 23. Israel and Saudi Arabia establish official diplomatic relations (70%) [38%] 24. US and China reach agreement to lift Trump-era tariffs (70%) 25. Slow Boring will exceed 10,000 paid members (70%) [75%]
What you really want is to have everyone answering the same questions. But that's not really what punditry is about. I don't even know what an "Apple Silicon" is, I don't claim to understand it, and my work as a blogger doesn't involve making any predictions about it. I will fail all questions that involve pontificating on "Apple Silicon", and that's fine. But that means you can't ask me and Matt Yglesias to answer the same set of questions to decide which of us is a "better pundit". In fact, you don't want to do this - part of being a good pundit is knowing what your areas of expertise are, and limiting yourself to them.
Arduino

Arduino is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "An off-the-shelf microcontroller board (e.g. RasPi Zero, Arduino) should be sufficient for that". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
Arduino
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
I think getting to a millisecond timing is not all that difficult. An off-the-shelf microcontroller board (e.g. RasPi Zero, Arduino) should be sufficient for that, no need for FPGAs.
aripiprazole

aripiprazole is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "The usual procedure is to take an SSRI and use an antipsychotic, probably aripiprazole or quetiapine, on the side". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
aripiprazole
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Antipsychotics are a class of drugs usually used against schizophrenia, but they also seem to have some role in depression. I hate using these because they have various concerning side effects if used for too long, but I will grudgingly include them at this part of the treatment algorithm. The usual procedure is to take an SSRI and use an antipsychotic, probably aripiprazole or quetiapine, on the side. Aripiprazole might make you restless, and quetiapine will make you sleep more and gain weight. Either one when used for too long increases your risk of metabolic problems (eg diabetes) and various terrible movement disorders (eg you can’t stop smacking your lips, and this problem never goes away). I don’t like these, but they sometimes work, and I can’t leave them out of the algorithm completely.
Asana

Asana is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 04, 2023 and January 04, 2023. The archive places it in contexts such as "He takes out his cell phone, opens the Asana app". It most often appears alongside AI Circle, Anthropic, Astra.

Reference entry
Asana
Mention count
1
Issue count
1
First seen
January 04, 2023
Last seen
January 04, 2023
January 04, 2023 · Original source
Max’s face lights up. “I never thought of . . . me, at an Innovation Forum? As a special guest? That would be amazing! Of course, I’m really busy next week . . . but I can tell them to put the gene splicing on hold, just for a little while - the suppliers won’t like it, but maybe if we scale down . . .” He takes out his cell phone, opens the Asana app, and starts rescheduling furiously.
Askinosie

Askinosie is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "I rank chocolates (#1 Askinosie". It most often appears alongside Alinea, Alp Blossom, Alpha Tolman.

Reference entry
Askinosie
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Which country has the world’s best health system? This is the type of question I usually love. I rank everything. I rank the 10 best meals I’ve ever had (#1 Alinea in Chicago, #2 Tanja Grandits in Basel, and #3 OCD in Tel Aviv). I rank chocolates (#1 Askinosie, #2 Dick Taylor of California, and #3 Fruition of New York. I rank Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom). I rank colleges. I rank academic departments of bioethics and health policy that compete with my own. I rank the meals I cook, the races I run, the bike rides I take, the speeches I give.
Assassins-Creed

Assassins-Creed is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as ""code me a Assassins-Creed-quality first person shooter game"". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Assassins-Creed
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
Some product like “AI plus an internal scratchpad” or “AI with stable memory” fulfills the promise of that model, and is useful enough that it gets released for some application: 50% CONQUEST OF DIGITAL MEDIA: Can we make an AI that will create a full-length major motion picture to your specifications? IE you give it $2, say "make a Star Wars / Star Trek crossover movie, 120 minutes" and (aside from copyright concerns) it can do that? What about "code me a Assassins-Creed-quality first person shooter game, with muskets, set in the Revolutionary War?" I don’t think we’ll get quite that far in five years, but I think maybe "short cartoony YouTube clip" or "buggy app-style game" could be possible. AI can make a movie to your specifications: 40% short cartoon clip that kind of resembles what you want, 2% equal in quality to existing big-budget movies.
Astral Codex Ten

Astral Codex Ten is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 01, 2026 and April 01, 2026. The archive places it in contexts such as "ask that he no longer use the Astral Codex Ten or Slate Star Codex brand". It most often appears alongside 1108 R St, 11841 Wagner Street, 131 Colonie Center.

Reference entry
Astral Codex Ten
Mention count
1
Issue count
1
First seen
April 01, 2026
Last seen
April 01, 2026
April 01, 2026 · Original source
Many cities have regular Astral Codex Ten meetup groups. Twice a year, I try to advertise their upcoming meetups and make a bigger deal of it than usual so that irregular attendees can attend and new readers can hear about the meetups. This is one of those times.
Meetup Czar Note: If Cassander claims to be running or hosting ACX Everywhere or the ACX Spring Schelling, this is false. We have fully split with Cassander, and ask that he no longer use the Astral Codex Ten or Slate Star Codex brand.
ATACMS

ATACMS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 22, 2024 and November 22, 2024. The archive places it in contexts such as "they gave Ukraine ATACMS". It most often appears alongside AI, Biden, Castro.

Reference entry
ATACMS
Mention count
1
Issue count
1
First seen
November 22, 2024
Last seen
November 22, 2024
November 22, 2024 · Original source
Suppose something important will happen at a certain unknown point. As someone approaches that point, you might be tempted to warn that the thing will happen. If you’re being appropriately cautious, you’ll warn about it before it happens. Then your warning will be wrong. As things continue to progress, you may continue your warnings, and you’ll be wrong each time. Then people will laugh at you and dismiss your predictions, since you were always wrong before. Then the thing will happen and they’ll be unprepared. Toy example: suppose you’re a doctor. Your patient wants to try a new experimental drug, 100 mg. You say “Don’t do it, we don’t know if it’s safe”. They do it anyway and it’s fine. You say “I guess 100 mg was safe, but don’t go above that.” They try 250 mg and it’s fine. You say “I guess 250 mg was safe, but don’t go above that.” They try 500 mg and it’s fine. You say “I guess 500 mg was safe, but don’t go above that.” They say “Haha, as if I would listen to you! First you said it might not be safe at all, but you were wrong. Then you said it might not be safe at 250 mg, but you were wrong. Then you said it might not be safe at 500 mg, but you were wrong. At this point I know you’re a fraud! Stop lecturing me!” Then they try 1000 mg and they die. The lesson is: “maybe this thing that will happen eventually will happen now” doesn’t count as a failed prediction. I’ve noticed this in a few places recently. First, in discussion of the Ukraine War, some people have worried that Putin will escalate (to tactical nukes? to WWIII?) if the US gives Ukraine too many new weapons. Lately there’s a genre of commentary (1, 2, 3, 4, 5, 6, 7) that says “Well, Putin didn’t start WWIII when we gave Ukraine HIMARS. They didn’t start WWIII when we gave Ukraine ATACMS. He didn’t start WWIII when we gave Ukraine F-16s. So the people who believe Putin might start WWIII have been proven wrong, and we should escalate as much as possible.” There’s obviously some level of escalation that would start WWIII (example: nuking Moscow). So we’re just debating where the line is. Since nobody (except Putin?) knows where the line is, it’s always reasonable to be cautious. I don’t actually know anything about Ukraine, but a warning about HIMARS causing WWIII seems less like “this will definitely be what does it” and more like “there’s a 2% chance this is the straw that breaks the camel’s back”. Suppose we have two theories, Escalatory-Putin and Non-Escalatory-Putin. EP says that for each new weapon we give, there’s a 2% chance Putin launches a tactical nuke. NEP says there’s a 0% chance. If we start out with even odds on both theories, after three new weapons with no nukes, our odds should only go down to 48.5% - 51.5%. (yes, this is another version of the generalized argument against updating on dramatic events) Second, I talked before about getting Biden’s dementia wrong. My internal argument against him being demented was something like “They said he was demented in 2020, but he had a good debate and proved them wrong. They said he was demented in 2022, but he gave a good State Of The Union and proved them wrong. Now they’re saying he’s demented in 2024, but they’ve already discredited themselves, so who cares?” I think this was broadly right about the Republican political machine, who was just throwing the same allegation out every election and seeing if it would stick. But regardless of the Republicans’ personal virtue, the odds of an old guy becoming newly demented each year is about 4% per year. If it had been two years since I last paid attention to this question, there was an 8% chance it had happened while I wasn’t looking. Like the other examples, dementia is something that happens eventually (this isn’t strictly true - some people reach their 100s without dementia - but I think it’s a fair idealized assumption that if someone survives long enough, then eventually their risk of cognitive decline becomes very high). It is reasonable to be worried about the President of the United States being demented - so reasonable that people will start raising the alarm about it being a possibility long before it happens. Even if some Republicans had ulterior motives for harping on it, plenty of smart, well-meaning people were also raising the alarm. Here I failed by letting the multiple false alarms lull me into a false sense of security, where I figured the non-demented side had “won” the “argument”, rather than it being a constant problem we needed to stay vigilant for. Third, this is obviously what’s going on with AI right now. The SB1047 AI safety bill tried to monitor that any AI bigger than 10^25 FLOPs (ie a little bigger than the biggest existing AIs) had to be exhaustively tested for safety. Some people argued - the AI safety folks freaked out about how AIs of 10^23 FLOPs might be unsafe, but they turned out to be safe. Then they freaked out about how AIs of 10^24 FLOPs might be unsafe, but they turned out to be safe. Now they’re freaking out about AIs of 10^25 FLOPs! Haven’t we already figured out that they’re dumb and oversensitive? No. I think of this as equivalent to the doctor who says “We haven’t confirmed that 100 mg of the experimental drug is safe”, then “I guess your foolhardy decision to ingest it anyway confirms 100 mg is safe, but we haven’t confirmed that 250 mg is safe, so don’t take that dose,” and so on up to the dose that kills the patient. It would be surprising if AI never became dangerous - if, in 2500 AD, AI still can’t hack important systems, or help terrorists commit attacks or anything like that. So we’re arguing about when we reach that threshold. It’s true and important to say “well, we don’t know, so it might be worth checking whether the answer is right now.” It probably won’t be right now the first few times we check! But that doesn’t make caution retroactively stupid and unjustified, or mean it’s not worth checking the tenth time. Can we take this insight too far? Suppose Penny Panic says “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans and it doesn’t happen. The next election cycle: “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans again and it still doesn’t happen. After her saying this every election cycle, and being wrong every election cycle, shouldn’t we stop treating her words as meaningful? I think we have to be careful to distinguish this from the useful cases above. It’s not true that, each election, the chance of Republicans becoming dictators increases, until eventually it’s certain. This is different from our examples above: Eventually at some age, Castro has to die, and the chance gets higher the older he gets.
ATACMS missiles

ATACMS missiles is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 18, 2022 and October 18, 2022. The archive places it in contexts such as "“Should we sent ATACMS missiles to Ukraine? It would have such-and-such benefits". It most often appears alongside 2024 elections, 5 U.S.C. §§ 558, 706, 538.

Reference entry
ATACMS missiles
Mention count
1
Issue count
1
First seen
October 18, 2022
Last seen
October 18, 2022
  • 22 October 18, 2022
October 18, 2022 · Original source
One of my hopes for forecasting is that it eventually becomes so well-validated that decision-makers can take these kinds of considerations into account: “Should we sent ATACMS missiles to Ukraine? It would have such-and-such benefits, but also increase the risk of nuclear escalation by 3.6%, is it worth it?” We can’t directly compare Samotsvety and Swift because they’re predicting over different time periods. But assuming that there’s more risk in the next six months than in the six months after that, I think Samotsvety is a little higher but they’re not embarrassingly far off. Metaculus is a bit more optimistic than either, believing there’s only a 4% chance of detonation in Ukraine in 2023 and a 7% chance of any use in the next ~year. Max Tegmark is going much higher than anyone else and says 16% chance of global nuclear war. Kalshi Applies For Election Markets Kalshi is a regulated and fully-legal prediction market with good lobbyists and a compliance team. This means the CFTC probably won’t randomly shut them down one day. But it also means they can only create new markets with CFTC permission. In July, Kalshi asked the CFTC for permission to make midterm election prediction markets - specifically, which party will win control of the House and Senate. The CFTC has said they will make a decision by October 28 (which doesn’t leave much time for predicting to happen before the November 8 election, but I guess it sets a precedent). September was the Request For Comment period, when the CFTC solicited comments from stakeholders about what they should do. Kalshi tried really hard to get lots of people to send in positive assessments - I know this because of how many people asked me “why is the CEO of Kalshi emailing me about this thing?” Their strategy seems to have worked; among the people who wrote to the CFTC in support were: A managing director at JP Morgan
Ativan

Ativan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam)". It most often appears alongside alcohol, allopregnanolone, allopregnanolone.

Reference entry
Ativan
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator! (or maybe that’s just an urban legend, I’ve never found proof either way) The discovery of endorphins (ie endogenous opiates) helped shed light on the brain’s reward system. So the discovery of a sort of endogenous benzodiazepine was pretty exciting. Maybe it’s some kind of master control switch for anxiety or something? Psychiatrists only know two ways to respond to an exciting new thing: publishing breathless studies claiming that it’s the true mechanism of action for SSRIs, and publishing breathless studies claiming that it’s the true biological basis of depression. This time, they did both: see eg Fluoxetine elevates allopregnanolone levels in female rat brain and The role of allopregnanolone in depressive-like behaviors. The basic theory was that stress / social isolation / etc → decreased allopregnanolone → something something BDNF and synaptogenesis → depression. And SSRIs → increased allopregnanolone → something something BDNF and synpatogenesis → recovery! Change the word “allopregnanolone”, and that’s every theory in psychiatry. But this particular theory had two extra pieces of evidence: premenstrual dysphoric disorder and postpartum depression. Remember, allopregananolone is a natural metabolite of the female hormone progesterone. Progesterone levels go up during pregnancy and the ~18th day of the menstrual cycle, then crash back down after delivery and the ~24th day of the menstrual cycle. Meanwhile, some women get depressed after delivering a baby, or on the ~24th day of their menstrual cycle. Suspicious! Maybe it’s because their progesterone was getting converted into allopregnanolone, an antidepressant hormone that affects mood! (why doesn’t every woman get PPD and PMDD? This study suggests that women with PMDD have altered sensitivity to allopregnanolone; plausibly people with PPD have some other form of altered sensitivity. In case you have the same question I do: the correlation between PMDD and PPD is not 100% but still pretty significant) History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Atlas Rugged

Atlas Rugged is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 21, 2022 and November 21, 2022. The archive places it in contexts such as "one of the suggestions is Atlas Rugged". It most often appears alongside 538, 538, Alameda.

Reference entry
Atlas Rugged
Mention count
1
Issue count
1
First seen
November 21, 2022
Last seen
November 21, 2022
November 21, 2022 · Original source
Polymarket again within 2% of Manifold. Only 23 traders here, and they’re a lot less optimistic than the Trump traders. FTX! 43 traders, seems like probably. I’ve seen a lot of Twitter takes about how rich well-connected people never get in trouble for this kind of thing, but the markets seem less cynical. 251 traders, and by the way amazing job by “mr22” who started this market on October 5. I also appreciate the relatively late end date - there’s another market “. . . by 2024” which is in the 30s, but that’s because people don’t trust the justice system to move quickly, not because they think he’ll be found innocent. There are a series of markets on sentence length which seem to suggest more than a month but less than a year in jail; this doesn’t really make sense to me and I’m going to nervously ignore them. Only 8 traders here, so take with a grain of salt, but this is a great example of the creative ways people are using Manifold. The market resolves not to “yes” or “no” but to the percent of FTX US users’ funds that they eventually get back; you make money if you were closer than other traders. Here they seem to think most people will only be getting about 14 cents on the dollar. There’s another market for FTX.US users which is a little higher at 29. 34 traders. I think this is too high; I bet it was some random third-tier insider, just because there are more of them and they’re under less scrutiny. Moving on to the effects on effective altruism in particular (just assume I have all possible conflicts of interest here): 272 traders, check the detailed resolution criteria. I think the strongest case is something like the one described in this article, about Center for Effective Altruism leaders discussing concerns about Alameda Research in 2018. The article doesn’t give specifics but my guess is they were the same issues Kerry Vaughn describes here (though see the followup comment by an employee who left FTX, casting doubt on Vaughn’s claims). That means the market hinges on whether Vaughn’s allegations fit the resolution criteria that “the unethical behavior must have been related to fraudulent investment strategies that involve spending other people's money without their permission”. Vaughn describes “poor capital controls, including a lack of distinction between money owned by investors and money owned by Alameda itself”, which sounds like it’s in that direction but could cover a wide variety of badness levels. My guess is everyone will end up agreeing that disgruntled Alameda employees whisper-networked that some things were bad about the company in 2018, some of the rumors got to CEA leaders, the leaders debated whether this was worse than normal for a tech startup, decided it didn’t rise to a level where they needed to publicly freak out, and moved on. Isaac will have to pay attention to the details as they come out and decide whether or not it qualifies. 45 traders. This seems to confirm that the CEA incident is responsible for most of the probability mass above; many fewer people think the FTX Future Fund (ie the charitable branch of FTX responsible for giving out their money) was in on this. Related: this market only has five traders, but I’m highlighting it anyway in the hopes that it gets more. The most money is on 2022. My guess is that we’ll find that they had terrible accounting practices in 2018-2019 of the sort that could be classified as criminally incompetent in a way that bled into fraud (but the trades went fine so nobody was harmed) and then they ramped it up a lot in 2022 to deal with the crypto crash. I think this market will be harder to resolve than people expect. 47 traders. Everyone is panicking about this possibility, but it looks like it’s not too likely. 10 traders. I’ll take this chance to say: a lot of media is predicting the death of EA, or a major blow to EA, or something in that category. Not going to happen. The media isn’t good at understanding people who do things for reasons other than PR. But most EAs really believe. Like, really believe. If every single other effective altruist in the world were completely discredited, I would just shrug and do effective altruism on my own. If they instituted the death penalty for effective altruism, I would do it under cover of night using ZCash. And I’m nowhere near the most committed effective altruist; honestly I’m probably below average. “Saint gets eaten by lions in Colosseum, can early Christianity possibly survive this setback?” Update your model or prepare to be constantly surprised. 6 traders. So, we lost several hundred million dollars of funding in a giant disaster which was also morally outrageous and demoralizing. It happens. But lots of people have already emailed me asking how to send in more money to help fill the gap. Some added something like “it was so depressing that all the FTX money meant my money didn’t make a difference, but now I can help again, and it’s great!” Can these people fill the hole? 32% chance that they can! 10 traders. And if they don’t, we’ll still probably do better than in 2021, before all the FTX money started rolling in. We’ll try harder to hammer in the point about not doing “ends justify the means” reasoning, and do some reorgs and purges to prevent anything like this from happening again, we’ll make a bunch of other changes - some reasonable, some panic-driven - but we’ll go on. If all the far-future stuff collapses, we’ll donate to global health charities. If the global health charities don’t work, we’ll fund GiveWell to sit around and figure out something that does. If GiveWell gets hit by an asteroid, we’ll work on asteroid deflection (actually I think we might already be doing that). If asteroid deflection turns out to be -EV, we’ll switch to shrimp welfare, or give ourselves Zika virus, or any of a million other things. You have no idea how committed we are to continuing to do effective altruism regardless of whether or not it’s “popular”. But it will be popular. 45 traders, resolution criteria at the link, notice the dip when the FTX news broke, followed by recovery as people had time to think it over more. Moving on to slightly less serious topics: The snapshot doesn’t show this, but one of the suggestions is Atlas Rugged. 67 traders, interesting to see where forecasters’ priorities lie. This was a big rumor early on, along with “everyone was on meth”, but the on site psychiatrist said it was false during an interview. 13 traders. WHY DO PEOPLE KEEP GOING ON PODCASTS? Midterms! That was two weeks ago? It feels like years! A week before the midterms, I wrote: Polymarket, Manifold, and PredictIt now have shiny interfaces for predicting the upcoming US midterm elections. In terms of the Republicans taking the Senate, Polymarket is at 65%, Manifold at 58%, PredictIt at 73%, and 538 at 49%. Congratulations 538! Mike Saint Antoine (who wrote the review of Viral in the last Book Review Contest) has put some more work into scoring midterm election forecasts. Here are some headline results: Mike writes: The reason I didn’t just do a three-way comparison between PredictIt, FiveThirtyEight, and Manifold Markets is that the Manifold Markets forecasts included fewer questions than the PredictIt and FiveThirtyEight forecasts. So in order to do a fair comparison here, I’ll be comparing the smaller subset of questions for which PredictIt and Manifold Markets both gave a forecast. So it looks like both Manifold and 538 did better than PredictIt, and there’s no clear way to tell which of the former did better. (except I guess you could do this analysis with just the subset of questions Manifold and 538 share, but Mike didn’t and I’m also not going to). PredictIt has a pretty consistent Republican bias (it’s a minor epistemic sin to accuse a prediction market of having a predictable bias unless you’ve made money exploiting it, I made $600 this election so I’ll let myself pass). In years when Republicans do better than expected, it will probably look better than other markets; in years when they do worse, it will look worse. Still, this is a bias, so I think we should take them doing worse this year as a fair reflection of their accuracy, even thought next year it could go the other way. My main two takeaways here are: PredictIt isn’t yet good enough that the ideal theorems showing prediction markets should be unbiased and better than everyone else apply to it. The obvious explanation is its $800-per-question cap. Polymarket doesn’t have that cap and it did better, although Mike hasn’t done a formal comparison to 538.
atomoxetine

atomoxetine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2021 and July 21, 2021. The archive places it in contexts such as "and adrenaline reuptake inhibitors (atomoxetine)". It most often appears alongside 9/11, ACOUP, Adderall.

Reference entry
atomoxetine
Mention count
1
Issue count
1
First seen
July 21, 2021
Last seen
July 21, 2021
July 21, 2021 · Original source
Living in Russia, I can say that ADHD (translated as СДВГ) is less recognized by the psychiatry community here because of its unclear aetiology. Doctors usually refuse to treat the patients in the absence of dangerous symptoms, and state the diagnosis as "organic nervous system disorder", "psychoorganic syndrome" or indeed "neurasthenia". Adderall and Ritalin are illegal drugs here. Patients usually get prescribed nootropics (glycine, racetams) and adrenaline reuptake inhibitors (atomoxetine).
Audi

Audi is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "one Audi that were made of aluminum". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Audi
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Musk’s word choice there—“obvious decision”—goes a long way toward explaining how he operates. Yes, the car needed to be light, and, yes, aluminum would be an option for making that happen. But at the time, car manufacturers in North America had almost no experience producing aluminum body panels. Aluminum tends to tear when worked by large presses. It also develops lines that look like stretch marks on skin and make it difficult to lay down smooth coats of paint. “In Europe, you had some Jaguars and one Audi that were made of aluminum, but it was less than five percent of the market,” Musk said. “In North America, there was nothing. It’s only recently that the Ford F-150 has arrived as mostly aluminum. Before that, we were the only one.”
Automated Land Acknowledger

Automated Land Acknowledger is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 17, 2023 and August 17, 2023. The archive places it in contexts such as "This is the prototype...The Automated Land Acknowledger". It most often appears alongside Alexander the Great, Amad, Amazon Echo.

Mention count
1
Issue count
1
First seen
August 17, 2023
Last seen
August 17, 2023
August 17, 2023 · Original source
“This is the prototype,” she tells you. “The Automated Land Acknowledger. I’ll be running a Kickstarter campaign next month.”
“Automated land acknowledger,” she repeats. “It seems so tokenist to just acknowledge land once, at the beginning of a meeting, then never talk about it again. You think the land stops being stolen from indigenous people just because you’re done with the preliminaries and have moved to reading off the minutes? The ALA has an adjustable setting for acknowledging Native land as frequently as you want, up to every thirty seconds.”
“This is the unceded ancestral land of the Ohlone people!" interrupts the Automated Land Acknowledger. You thought it had been turned off, but they must have just changed the settings.
AutoRegex

AutoRegex is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 29, 2022 and July 29, 2022. The archive places it in contexts such as "AutoRegex is a GPT-3-based app that converts natural language descriptions into regular expressions". It most often appears alongside /r/forcedbreeding, /r/forcedbreeding, Adrian D’Souza.

Reference entry
AutoRegex
Mention count
1
Issue count
1
First seen
July 29, 2022
Last seen
July 29, 2022
July 29, 2022 · Original source
7: AutoRegex is a GPT-3-based app that converts natural language descriptions into regular expressions, ie "B followed by 2 vowels followed by ld" → "B[aeiou]{2}ld". I think this is the first AI-based app I might use in real life, good work.
AWS Cognito

AWS Cognito is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "I would probably implement with AWS Cognito". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
AWS Cognito
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
As others have stated, a CRUD for creating the tests wouldn't be hard, though we'd have to think about how exactly the configurability would work. And then there would be adding identification and authorization, which I would probably implement with AWS Cognito.
AZ

AZ is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 16, 2021 and February 16, 2021. The archive places it in contexts such as "we’ll find that P/M, Novavax, AZ, and J&J all cut deaths". It most often appears alongside AIDS, B117 strain, Brazil.

Reference entry
AZ
Mention count
1
Issue count
1
First seen
February 16, 2021
Last seen
February 16, 2021
February 16, 2021 · Original source
In terms of preventing sympomatic infections, the best current data suggests that the Novavax vaccine is 96% effective against Coronavirus Classic, 86% effective against UK, and 60% effective against South Africa. AstraZeneca is something like 80% effective against Classic, 65% effective against UK, and the South African study was kind of bungled but our best guess is "seems pretty bad". Johnson and Johnson is 66-72%+ effective against Classic and 57% effective against South Africa. Pfizer/Moderna hasn't been tested against South Africa in real life yet, but lab studies suggest slightly decreased efficacy.
B83

B83 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 07, 2022 and January 07, 2022. The archive places it in contexts such as "the biggest weapon in current US inventory is the 1.2 megaton B83". It most often appears alongside ACX Discord, Aerojet XLR-132, Aimable.

Reference entry
B83
Mention count
1
Issue count
1
First seen
January 07, 2022
Last seen
January 07, 2022
January 07, 2022 · Original source
Assuming this is a 9-km comet of typical composition, "aimed" at a spot 70% of the distance from the midpoint of the Earth to its periphery, with Our Heroes having perfect knowledge of all of this, then deflecting the comet to barely miss skimming the Earth's atmosphere given six months' notice would require approximately 220 megatons of military-surplus thermonuclear weapons. You wouldn't want to use anything bigger than 5 megatons for this, and the biggest weapon in current US inventory is the 1.2 megaton B83, so call it two hundred of those just to be safe.
babbel

babbel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "Toucan by babbel language"; "Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
babbel
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one. There are a few different ones out there.
Baby Einstein

Baby Einstein is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 18, 2021 and February 18, 2021. The archive places it in contexts such as "It starts with parents buying Baby Einstein tapes". It most often appears alongside American education, Appalachian, Bezoses.

Reference entry
Baby Einstein
Mention count
1
Issue count
1
First seen
February 18, 2021
Last seen
February 18, 2021
February 18, 2021 · Original source
One one level, the titular Cult Of Smart is just the belief that enough education can solve any problem. But more fundamentally it's also the troubling belief that after we jettison unfair theories of superiority based on skin color, sex, and whatever else, we're finally left with what really determines your value as a human being - how smart you are. DeBoer recalls hearing an immigrant mother proudly describe her older kid's achievements in math, science, etc, "and then her younger son ran by, and she said, offhand, 'This one, he is maybe not so smart.'" DeBoer was originally shocked to hear someone describe her own son that way, then realized that he wouldn't have thought twice if she'd dismissed him as unathletic, or bad at music. Intelligence is considered such a basic measure of human worth that to dismiss someone as unintelligent seems like consigning them into the outer darkness. So DeBoer describes how early readers of his book were scandalized by the insistence on genetic differences in intelligence - isn't this denying the equality of Man, declaring some people inherently superior to others? Only if you conflate intelligence with worth, which DeBoer argues our society does constantly. It starts with parents buying Baby Einstein tapes and trying to send their kids to the best preschool, continues through the "meat grinder" of the college admissions process when everyone knows that whoever gets into Harvard is better than whoever gets into State U, and continues when the meritocracy rewards the straight-A Harvard student with a high-paying powerful job and the high school dropout with drudgery or unemployment. Even the phrase "high school dropout" has an aura of personal failure about it, in a way totally absent from "kid who always lost at Little League".
BadCorp

BadCorp is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 06, 2023 and December 06, 2023. The archive places it in contexts such as "BadCorp’s $50 Alzheimers drug". It most often appears alongside Adderall, anarcho-primitivists, BadCorp.

Reference entry
BadCorp
Mention count
1
Issue count
1
First seen
December 06, 2023
Last seen
December 06, 2023
December 06, 2023 · Original source
BadCorp takes whatever was in their fridge, blends it together, calls it “a revolutionary new Alzheimers drug”, conducts a bad study which they manipulate, and does a great advertising blitz. Their drug costs $50. Which one does your doctor prescribe you?
…or maybe your insurance covers BadCorp’s $50 Alzheimers drug and not GoodCorp’s $10,000 Alzheimer’s drug, and you buy that policy anyway, because nobody looks into the details of Alzheimers drug coverage when they’re buying an insurance policy unless they have Alzheimers (and if they do, it’s too late). And even if they did look, BadCorp would have a smokescreen of well-done fake studies such that it was hard to tell they were worse than GoodCorp.
Bally

Bally is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 14, 2021 and May 14, 2021. The archive places it in contexts such as "Bally, a casino company, targets 3.5 seconds per game". It most often appears alongside Addiction by Design: Machine Gambling in Las Vegas, Amazon, American Gaming Association.

Reference entry
Bally
Mention count
1
Issue count
1
First seen
May 14, 2021
Last seen
May 14, 2021
May 14, 2021 · Original source
First came the obvious optimizations. These are optimizations any hotshot business consultant would suggest. Designers replaced mechanical levers with buttons and physical reels with video screens. This made the games three to four times faster. The quicker each game, the more money gamblers can spend during their gambling session. Quicker games are also more addictive. Bally, a casino company, targets 3.5 seconds per game.
bamlanivimab

bamlanivimab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 23, 2021 and November 23, 2021. The archive places it in contexts such as "including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid". It most often appears alongside 1/6 insurrectionists, Ahmed, Alabama.

Reference entry
bamlanivimab
Mention count
1
Issue count
1
First seen
November 23, 2021
Last seen
November 23, 2021
November 23, 2021 · Original source
Author appears to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid.
The steps required to accept the no-significant-effect outcome are extreme — one needs to find a reason to exclude most of the studies, disregard the strong treatment-delay response relationship, and disregard all prophylaxis studies. Even after this, the result is still positive, just not statistically signficant. This does not support a negative recommendation. Widely accepted and effective (subject to dependence on viral variants) treatments like casirivimab/imdevimab, bamlanivimab, and sotrovimab were all approved without statistically significant mortality benefits.
First, the claim that I "[appear] to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid." They suggest I am turning my readers away from other treatments including ones that are already standard of care in western health systems.
bapineuzumab

bapineuzumab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "earlier antibodies that saw only failure in phase 3 – bapineuzumab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
bapineuzumab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
[83] S. Salloway et al., “Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease,” New England Journal of Medicine, vol. 370, no. 4, pp. 322–333, 2014, doi: 10.1056/NEJMoa1304839.
[84] R. Vandenberghe et al., “Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials,” Alzheimer’s Research & Therapy, vol. 8, no. 1, p. 18, May 2016, doi: 10.1186/s13195-016-0189-7.
barbed wire

barbed wire is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 08, 2021 and April 08, 2021. The archive places it in contexts such as "the invention of barbed wire in 1874". It most often appears alongside ACX, amoral familialism, An Introduction to Law and Economics.

Reference entry
barbed wire
Mention count
1
Issue count
1
First seen
April 08, 2021
Last seen
April 08, 2021
April 08, 2021 · Original source
So Ellickson argues that the Shasta County trespass norms support the hypothesis.9 He also makes a prediction here that things were different in the mid-nineteenth century. “During the early history of the state of California, irrigated pastures and ranchettes were rare, at-large cattle numerous, and motorized vehicles unknown. In addition, a century ago most rural residents were accustomed to handling livestock. Especially prior to the invention of barbed wire in 1874, the fencing of rangelands was rarely cost-justified. In those days an isolated grower of field crops in Shasta County, as one of the few persons at risk from at-large cattle, would have been prima facie the cheaper avoider of livestock damage to crops.” And so the farmer would have been responsible for fencing animals out, and borne the costs if he failed to.
Bard

Bard is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa"; "twelve LLMs - including Bard". It most often appears alongside Asterisk, Berkeley, Bitcoin.

Reference entry
Bard
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
Beast Academy

Beast Academy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Many schools use tools like iXL, Beast Academy and Amira". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Beast Academy
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Same state curriculum, same worksheets, same pace. The school philosophy was “no acceleration—just go deep.” We knew this was the philosophy going in. The pitch was that instead of accelerating through the state curriculum the teachers would take their time with the kids and allow them to fully explore and master the content of each grade. When we asked for examples of what that meant in practice we were told things like: “Instead of reading more advanced vocabulary, the students will learn to read out loud and use emotion and character impressions. They will learn how to vary the timing of their reading like where and when to pause to create emotion in the listener”. That sounded reasonable! It sounded like more learning, but just different learning than what the state had mandated. In practice that was not what happened. In practice “deep” just meant “un‑measured.” Smart kids + small classes ≠ accountability. The kids had time to do music, lego building, theatre and Friday ski trips because they were all really bright. They didn’t need 6+ hours a day to learn the limited math required by the state, and since the school did not feel the need to advance faster than the state, there was no pressure to push learning at all – on anything really. There was no overall school curriculum. Every teacher did their own thing. While one first grade class had weekly spelling bees, the teacher in the other classroom did not believe in learning spelling at all. But it didn’t matter. The metrics they measured the kids on in both classes advanced “enough” that no one was concerned. Most time wasn’t spent on math or language anyway. Beyond the brochure activities like skiing and theater and the four hours of foreign language per week they split between Spanish and Mandarin (which was really a great opportunity for the kids who already spoke Spanish and Mandarin to have their egos flattered. I did not see any learning in either language class. I don’t see how you can teach a language a couple of hours a week to a group of 18 kids with skill levels from zero to fluency and expect to have any impact), a lot of time was spent on DEI. DEI was pitched as helping kids handle the emotions that often come from being sensitive gifted children (they called it “Synapse”). In practice my oldest daughter got four years of learning about the basic ideas of Martin Luther King Junior and Rosa Parks, a rough understanding that some people are non-binary, and a great deal of anxiety every time I left the water running while I was brushing my teeth. The talent drain In Spring 2024 the “intermediate-school” head resigned, as did the 40+ year veteran science teacher we had been looking forward to our daughter having, the beloved tech teacher who had built a her own proprietary “learn to type” software, plus half the lower‑school faculty. Our oldest was going to be entering fourth grade; her incoming roster read like a rebuilding year for a professional sports team. It was possible we could get her into a middle school that would feed into a top tier high school, but those did not start until 5th grade. Our best option looked like “suck it up and accept whatever we had for at least a year”. One option was to do something radical. We considered taking a GAP year and traveling the world with an organization called “Boundless” but decided the timing wasn’t right. Earlier in the year we had started exploring moving to the charter city of Prospera. There is a Montessori school there that seemed like it might be alright. And we could surround the kids with an interesting group of people (and live on the beach!). But by the spring we had ruled it out. There did not seem to be many families as part of the community and we were not comfortable with the risk profile based on what was happening with the conflict between Honduras and their charter cities. Then I stumbled across Alpha: Two‑hour mornings, life‑skills afternoons, claims of 2x learning. Marketing copy is cheap; still, the promise was different enough to warrant due diligence. The initial plan was to fly some of the kids to Austin for an Alpha summer camp for a week in June – just to try it out. But once we started exploring more my wife asked me: “Could we actually move to Austin and try it for a year? Based on what is happening at the kids' school, this might be the year to try it.” So over eight weeks we flew to Austin five times – conversations with admissions and school heads, real estate searches, kids doing shadow‑days. Every parent we spoke to was very impressed with the school. Their kids really were advancing at 2x+ speed – and no one believed it was just a “selection effect”. And every guide I spoke to was extremely impressive themselves. They reminded me of the staff you run into when visiting Disney World. They all seemed “full faced” and fully-engaged. When I asked the head of admissions how they found such good staff he told me their compensation was fully transparent. “Associate Guides” were paid $60,000/year (vs the $40,000 average for Austin teachers), “Full Guides” made $100,000 and the five “Head Guides” in the school each made $150,000. They were able to both poach the best teachers from other schools, but also bring exceptional people into teaching that would not have considered it otherwise. It also let them have very high expectations for teachers once they were hired. We pulled the trigger in July. New house. Admissions letter signed. Moving truck (plus car-mover) scheduled for October. Worst case, it would be a one‑year sabbatical from stagnation. The hypothesis I carried south Elite private school attendance buys you smaller classes, brighter kids, and fancier field trips – not academic acceleration. If Alpha was real, we’d see that differential, measurable impact by Christmas – that was when we would need to decide if we would cut bait and re-apply to schools back home (and sign the kids up for more IQ-tests. The school would not accept old ones). That prior—show me velocity, not polish—is the lens through which the rest of this review should be read. Part Two: A History of Alpha Note: This is my best attempt at piecing together the history of the school based on conversations with co‑founder MacKenzie Price, high school head Chris Locke, Alpha staff, and Alpha parents; All dates are estimates and I am SURE I have gotten some details wrong. I will come back after the fact in the comments and make corrections as I hear from the people involved with corrections. 2013 – 2017 | Garage‑School to “Alpha” MacKenzie Price, then a mortgage broker in Austin, wasn’t impressed by the city’s gifted programs. She invited a small number of neighbourhood kids (including her two) into a makeshift microschool that ran two intense, teacher‑led academic “sprints” each morning, then “life‑skills” projects after lunch. Joe Liemandt — Founder of Trinity Technology, ESW Capital billionaire and family friend (MacKenzie’s husband worked for him) — kept his own children in conventional private school until he saw the qualitative improvement in the life skills of MacKenzie’s kids. He decided he wanted his kids to join MacKenzie’s but he wanted to take the project to the next level. Sometime around 2014-2017 he joined MacKenzie as a co-founder and started writing checks. Alpha recruited more students and guides and the operation jumped from location-to-location looking for a larger permanent home. 2017 – 2020 | K-8 Expansion and 2-hour focus Alpha grew to roughly 90 students from K‑8 and stabilized. Morning “core blocks” were still teacher‑driven (20‑minute bursts, 5‑minute breaks, rinse, repeat), but focused on students engaged in exercises with rapid feedback (not lectures). Afternoon workshops covered “life skills” like how to give and receive feedback or public speaking. I have not seen academic data from this time period, but when I spoke to Chris Locke, head of Alpha’s high school (which launched around 2020), he told me the kids coming into his 9th grade program were “fine,” academically – it was their life skills, confidence, and ability to engage with adults and their peers were exceptional. At this stage no AI, no dashboard, no 2x learning, no portal — just better ratios and focused pacing and the result was well balanced kids who were enjoying their education experience (even if they were unexceptional academically). 2020 – 2022 | Platform Era Begins Somewhere along the way Liemandt hired a small engineering team to stitch together edtech learning tools. Many schools use tools like iXL, Beast Academy and Amira. Those tools fit in well with the 2-hour structured approach Alpha was using. The “platform” Liemandt’s team built was meant as a tool to free up guide time so that students could be more self-directed. The dev team stitched together the preferred off‑the‑shelf apps behind a single login, and built out tracking and dashboards so guides (and students) could easily see how they were progressing. This also gave the curriculum team (there was a curriculum team now) data to understand where students were spending their time, what tools were working, and which weren’t as effective. The Alpha Portal was born. Not only did it increase efficiency, it provided data to iterate with. Chris Locke saw the curve change incrementally: each new cohort of ninth‑graders under the new tech-enabled learning platform came in a little stronger academically. The “life skills” were now being matched by the “academic skills”. 2022 | Expansion and Iteration By having access to Alpha kids post-graduation in the high school, Locke could send feedback back to the elementary school.The kids coming out of the new program were now killing it academically on Math, Language, and Science, but they were still weak on things like History and Geography. He fed that type of information back to the curriculum designers, who iterated and improved the program. Soon, in addition to the core platform that directed students to third-party tools, the tech team was building proprietary “Alpha” tools themselves. The flagship of the in-house tools was “AlphaReads”. AlphaReads requires students to read progressively more complicated passages, followed by answering reading comprehension questions. In addition to helping the kids improve reading skills, Alpha uses it to push types of content. Instead of classes in history, geography, economics and political science, some of the reading passages will cover that material (in addition to learning how to read and understand Shakespeare and Proust). The success of the 2-hour learning platform was giving the Alpha founders confidence. Liemandt in particular wanted to see if the program had legs beyond the elite group of students being educated in Austin. Alpha’s first external test in August 2022 in Brownsville, TX – a small community on the Mexico border with less than half the per capita income of Austin. SpaceX had recently launched Starbase in Brownsville in 2014 and the employees there were not happy with the existing school options. Someone at SpaceX approached Alpha and asked if they could launch a new campus for their employees. It is unclear if any money changed hands, but when Alpha launched their Brownsville campus (available to SpaceX employees and any other locals who are interested) tuition was only $10,000 (vs $40,000 at the main Austin campus); incoming students trailed national academic standards by over a year. But after nine months on the Alpha program the first cohort of students had caught up and surpassed the national average, and they kept accelerating, achieving an average learning velocity of ~2× the national average (see section four for what that means). Brownsville was Alpha’s attempt to show that their model wasn’t just rich‑kid selection effects. Spring 2024 | Field Pilots & Ukraine Trip Alpha tuition is high for the Austin area ($40,000 vs average private school ~$10,000-$15,000), but unlike most private schools tuition is all-inclusive. There are no extra fees for computers or field trips. There are no silent auctions or appeals for donations. This “no extra fees” allows the school to do some pretty ridiculous things. In the first half of 2024 Alpha sent a group of students to Poland to help launch a 2-hour learning pilot among Ukrainian refugees. Students did not pay to go on the trip. But students also did not have a “right” to go on the trip. They had to earn it. In addition to being on top of academic and non-academic expectations, students who wanted to participate had to learn basic Ukrainian so they could interact with the students in Poland they were meant to be helping. By not linking the opportunity to payment, the school could instead link it to behavior and achievement. This year a group of kids who learned to sail during the school year are going on a sailing trip through the Caribbean – for no additional fees to the parents. I also heard that around this time Alpha began testing the 2-hour learning platform at a facility for juvenile delinquents in Florida. I heard that from one individual who was not directly involved and I have not found any written documentation on it, so unclear if it worked, it was a one off, or if it even happened. But it fits into the pattern of Alpha at this stage: “We know this program works for a specific type of kid. Let’s find out how broadly it is applicable. Can it work for everyone? Is it the solution for learning and education for the world?” Fall 2024 | “Pick‑Your‑Afternoon” Specialist Schools MacKenzie told me that there was consensus among the current parents of Alpha that the 2-hour learning program was exceptional and was making a huge difference with their kids. Their kids were all learning at breathtaking speed in a very condensed period of time. But there was NOT consensus about what the kids should be doing in the other 22-hours of the day. Some parents wanted to utilize the platform’s capabilities to go even faster. Some wanted their kids to just chill out and enjoy the rest of their day – let kids be kids. Others wanted their kids to use the freed up time to do sports, or study music. It was clear to her that “learn more faster in a short period of time” was a universal desire. But beyond that it was unclear what the “right” solution for the rest of her program was. You can make the morning ultra-personalized, but if the goal of the afternoon is socialization that you are missing in the morning, you need to have some sort of alignment on how to spend that afternoon. That challenge led to Alpha’s 2024 expansion into specialty schools. Three micro‑campuses opened August 2024: GT School (Georgetown, TX) — Alpha’s “Gifted and Talented” School. Higher admissions bar; higher academic expectations; Afternoon programming focused on excelling in “academic competitions” like chess, go, debate, public speaking, robotics, programming and Quiz Bowl.
Ben & Jerry's

Ben & Jerry's is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 24, 2022 and June 24, 2022. The archive places it in contexts such as "Ben & Jerry's thinks NATO should chill a little over Ukraine". It most often appears alongside 501(c)(3), 80,000 Hours, 9/11.

Reference entry
Ben & Jerry's
Mention count
1
Issue count
1
First seen
June 24, 2022
Last seen
June 24, 2022
June 24, 2022 · Original source
...al question relies on their ruling territories, not elections. - Pax Americana had been so strong that even American ice-cream companies have foriegn policy priorities — Ben & Jerry's thinks NATO should chill a little over Ukraine .
Benzedrine

Benzedrine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice"; "children ... got diagnosed and given Benzedrine". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
Benzedrine
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
Treating ADHD with amphetamines was hardly a new invention. Psychiatrists had been doing it since the 1930s, albeit with slightly different drugs. Remember, many organic chemicals come in two versions, a "right-handed" or "d" version and a "left-handed" or "l" version. Benzedrine (a 50-50 d/l split) and Dexedrine (pure d-amphetamine) were the treatments of choice throughout the mid-20th century. So why was it Adderall - a weird combination of four different salts selected kind of at random by a sketchy diet pill company - that caught on?
I'm not sure. My best guess is good timing plus good advertising. In the early 20th century, ADHD was called "minimal brain dysfunction" and diagnosed only in the most extreme cases. A few children with absolute and total inability to function at all got diagnosed and given Benzedrine or Dexedrine; everyone else was left to fend for themselves. As far as I know, this wasn't because doctors had a principled commitment only to diagnose extreme cases - I found a paper from 1975 arguing that up to 5 - 10% of children probably had minimal brain dysfunction, the same number estimated to have ADHD today. Parents just didn't know about it and didn't really have "take my kid to a psychiatrist" in their set of plausible options to consider.
beta-blockers

beta-blockers is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 24, 2024 and April 24, 2024. The archive places it in contexts such as "The 1970s had some okay blood pressure medications, like the beta-blockers". It most often appears alongside 2008 America, @agoodmanbacon, Baicker.

Reference entry
beta-blockers
Mention count
1
Issue count
1
First seen
April 24, 2024
Last seen
April 24, 2024
April 24, 2024 · Original source
Source here. The odds of death within 30 days of a heart attack have fallen from 20% in 1995 to 12.4% in 2015 (source). This is also no mystery; the improvement comes from increased use of basic drugs like ACEIs, aspirin, and beta-blockers, plus more advanced interventions like thrombolytics and angioplasties, plus logistical improvements like more heart attack patients being placed on specialized cardiac wards. Again, can we dismiss this because maybe heart attack victims are younger? The study this particular graph comes from says their patients were on average 2.7 years older at the end than the beginning, so here age effects seem to point in the opposite direction. Here’s a graph showing the same decline if you break it up by under- and over-65s, though I wish I could find something with smaller bins. Same data for stroke: Source here. Note that these are age-adjusted data! In 2000, a stroke victim is only half as likely to die in the first two years after their illness as they were in 1980. Here we don’t have to worry about age effects at all; the graph is already adjusted for age. You can see similar survival rate increases for other conditions like congestive heart failure (5-year survival rate went from 29% to 60% since 1970), multiple sclerosis (standardized mortality rate went from 3.1 to 0.7 since 1950), type 1 diabetes (survival rate at 50 from about 40% to 80% since 1950) and nearly any other condition you look up. I’m harping on this because it’s in some sense the central example of medicine: you get some deadly disease like cancer, and you want to know if doctors can help you survive or not. All the evidence suggests medicine has gotten much better at this in the past fifty years. Robin’s going to have a lot of hard-to-interpret studies about what happens to your cholesterol score or whatever after you change insurance, and we’ll pick these apart, but to me this seems like a much less central example of “does medicine work?” than the fact that we’re curing cancer and increasing heart attack survival rates. III. RAND Health Insurance Experiment This is considered the canonical study on the effect of health insurance. In the 1970s, RAND gave thousands of people one of five types of insurance, ranging from very bad (barely any coverage until a family reached a deductible of $1000, ie $5000 in today’s dollars) to very good (all care was free). Then they waited eight years. Then they checked whether the people on the good insurance ended up any healthier than the people on the bad insurance. The paper I found measured five questionnaire-based outcomes plus five objective physiological measures, for a total of ten outcomes (Robin says he has a book where they discuss 23 to 30 outcomes, but I don’t have that book, so I’m sticking with the paper). The ten in the paper I read were: Physical functioning questionnaire
Blood pressure They found no effect of insurance on any of the questionnaires, and modest positive effects on vision and blood pressure. How surprising is this? It seems moderately surprising that nobody improved on any of the questionnaires. These seem to measure overall health. Maybe they were bad measures? Maybe 10,000 mostly-healthy people over 8 years doesn’t provide enough power to detect health improvements on questionnaires? I’m not sure. It doesn’t seem surprising to me that nobody improved on smoking, weight, or cholesterol. The 1970s didn’t have any good anti-smoking medication - even the nicotine patch wasn’t invented until after this study was finished. Likewise for weight loss - the 1970s were in the unfortunate interregnum between the fall of methamphetamine and the rise of Ozempic. There were some weak cholesterol medications back then - eg nicotinic acid - but they were rarely used, and doctors weren’t even entirely convinced that cholesterol was bad. For all three of these things, the 1970s state of the art was doctors saying “You should try to stop smoking and eat better.” RAND found that the better insurances led to 1-2 more doctor visits per year. I don’t think that 3 visits to a doctor saying “You should try to stop smoking and eat better” vs. 4 visits to that doctor is going to affect very much. It’s also not surprising that vision improved; the good insurances were more likely to cover glasses, and everyone knows that glasses help your vision. Even Robin admits this is a real effect; he just classifies it as more physics than medicine. Blood pressure is more debatable. The 1970s had some okay blood pressure medications, like the beta-blockers, and doctors weren’t afraid to use them. So it seems possible in theory that better medical care could lead to decreased blood pressure. Still, Robin is skeptical. He says that the improvement in blood pressure found during the study was p = 0.03. In a study with 30 measures, one will be positive at 0.03 by coincidence. The version of the study he’s reading has 30 measures (mine has 5 - 10, depending on how you count the questionnaire). On the other hand, this paper looks into the blood pressure result in more detail. It finds that “plan effects on blood pressure” were three times higher for hypertensives for non-hypertensives; that is, unlike statistical flukes (which we would expect to affect everyone equally), the effect was concentrated in the people we would expect doctors to treat. It also finds that plan effects are higher for poor people; unlike statistical flukes (which would affect everyone equally), the effect was concentrated in the people we would expect insurance to help. And it finds pretty convincing intermediating factors: people with good insurance were 20 percentage points more likely to get hypertension treatment, p < 0.001). So I think it’s a stretch to attribute this one to random noise. This is the study authors’ conclusion as well. They calculate the benefit from this blood pressure improvement and find that: If 1,000 fifty-year-old men at elevated risk were enrolled on a free rather than a cost-sharing plan, then we would anticipate that about 11 of them, who would otherwise have died, would be alive five years later. Still, they describe their study as having a negative result, because: ...these mortality reductions, in and of themselves, are not sufficient to justify free care for all adults. I assume they’re working off of some kind of reasonable cost-effectiveness model for government spending here. Still, if I were a fifty year old adult, I might be willing to personally spend a few hundred extra dollars a year to increase my 5-year-survival-rate by 1%. Certainly I don’t think it’s fair to describe this as “RAND proves medicine doesn’t work.” Robin has a book with more information than I could get from the papers, so I feel bad contradicting him on this one. I’m more confident in my discussion of the next two experiments, which I think are clear enough that we can go back to this one later and apply what we’ve learned. IV. Oregon Health Insurance Experiment In 2008, Oregon had extra money and decided to expand Medicaid, a free insurance program for poor people. Many people applied for the free insurance, the state ran out of money, and they distributed the available Medicaid slots by lottery. This made the expansion a perfect setup for a randomized controlled trial on whether government-provided free insurance helps the poor. Scientists monitored the recipients for two years (why not longer? I think at some point the insurance coverage stopped) and found that the people with Medicaid did in fact use more medical care than the control group. For example, only 69% of the control group described themselves as getting all the medical care they needed, but 93% of the group with insurance did. People with the insurance used more of almost all categories of medication: People who got the free insurance had less medical debt at the end of the study period. They described themselves on questionnaires as having better health (55% vs. 68% at least “good”, p < 0.0001), and were more likely to say their health had improved over the past few months (71% vs. 83%, p < 0.001). They described having better mental health and less depression (25% vs. 33% depressed, p = 0.001). However, Robin notes that many of these subjective changes happened immediately, ie before they even had a chance to use their new insurance. This means they’re more likely to represent mood affiliation (eg “I have insurance now, so I’m optimistic about my health!”). There was no difference on objective health measures, including blood pressure, cholesterol, and HbA1c (a measure of blood sugar / diabetes control). Why not? The authors do the math on diabetes. If you look at the graph above, you see that about 12.5% of controls vs. 17.5% of experimentals took diabetes medications, p < 0.05. Studies find that diabetes medications decrease HbA1c by about one percentage point (normal HbA1c is about 5%, so this is a lot). If 5% of the insurance group took diabetes medications and decreased their HbA1c by 1 pp each, then the HbA1c of the experimental group would decline by 0.05 pp compared to the control group. Their 95% confidence interval of the difference was (-0.1, +0.1 pp), which includes the predicted value. So when they say “insurance didn’t significantly change HbA1c”, what they mean is “the change in HbA1c is completely consistent with the consensus effect of antidiabetic medications”. Could the same be true of the other results, like hypertension? We find that the experimental group was 1.8 percentage points more likely to get a hypertension diagnosis, 0.7 percentage points more likely to get hypertension medications, and had 0.8 points lower blood pressure - but that all of these numbers were nonsignificant. If we take the nonsignificant numbers seriously, 0.7 pp taking antihypertensives caused an 0.8 point blood pressure drop in the full sample, meaning that antihypertensives caused a 100 point blood pressure drop in each user. This definitely isn’t true - a 100 point blood pressure drop kills you - but it means that a plausible pro-medicine result like antihypertensives lowering blood pressure 10 point is well within the study’s confidence interval. Maybe the anti-medicine position is that, for some reason, good insurance doesn’t lead to hypertension diagnosis or antihypertensive medication use? If I understand these numbers right, about 22% of Americans have blood pressure > 140/90, the level at which doctors recommend medication. I expect the marginally-insured poor people in this experiment to be less healthy than average, so let’s say 25 - 30%. In the experiment, about 13.9% of the control group and 14.6% of the experimental group got antihypertension medication. Why so low? This study found that only about 60% of participants in the Oregon study who got the insurance even went to the doctor for non-emergency reasons! Subtract out the ones who refused to take antihypertensives, or who have too many side effects, or whose doctors let this fall through the cracks, and I think the 13 - 15% numbers make sense. This study found that insurance increased hypertension medication use by a central estimate of 0.7 pp, not significant, confidence interval -4.5 to 5.8. Let’s take a convenient central estimate of our likely hypertension rate and say that 28% of our population should have gotten hypertension meds. That means the central estimate increased the percent of people who got recommended hypertension meds from 50% to 53%, and the 95% confidence interval includes up to 71%. So my assessment of the blood pressure results from this study is: At the beginning of the study, about 50% of people who should have been on hypertension meds were. The study had too low power to really figure out how this changed, but the central estimate is +3%, and the 95% CI rules out improvements beyond +21%
Beyond Meat

Beyond Meat is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2023 and March 08, 2023. The archive places it in contexts such as "mix a little cultivated meat with ... Beyond Meat"; "Impossible or Beyond Meat". It most often appears alongside ACX, Adventist studies, ALLFED.

Reference entry
Beyond Meat
Mention count
1
Issue count
1
First seen
March 08, 2023
Last seen
March 08, 2023
March 08, 2023 · Original source
Is Cultivated Meat For Real?, by Robert Yaman. I’d heard claims that cultivated (eg vat-grown, animal-cruelty-free) meat will be in stores later this year, and also claims that it’s economically impossible. Which are true? This article says that we’re very far away from cultivated meat that can compete with normal meat on price. But probably you can mix a little cultivated meat with Impossible or Beyond Meat and get something less expensive than the former and tastier than the latter, and applications like these might be enough to support cultivated meat companies until they can solve their technical obstacles.
BFR

BFR is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "SpaceX has launched BFR to orbit". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
BFR
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
1. Widely accepted paper claims a polygenic score predicting over 25% of human intelligence: 70% 2. …50% or more: 20% 3. At least one person is known to have had a “designer baby” genetically edited for something other than preventing specific high-risk disease: 10% 4. At least a thousand people have had such babies, and it’s well known where people can go to do it: 5% 5. At least one cloned human baby, survives beyond one day after birth: 10% 6. Average person can check their polygenic IQ score for reasonable fee (doesn’t have to be very good) in 2023: 80% 7. At least one directly glutamatergic antidepressant approved by FDA: 20% 8. At least one directly neurotrophic antidepressant approved by FDA: 20% 9. At least one genuinely novel antipsychotic approved by FDA: 30% 10. MDMA approved for therapeutic use by FDA: 50% 11. Psilocybin approved for general therapeutic use in at least one country: 30% 12. Gary Taubes’ insulin resistance theory of nutrition has significantly more scholarly acceptance than today: 10% 13. Paleo diet is generally considered and recommended by doctors as best weight-loss diet for average person: 30% 14. SpaceX has launched BFR to orbit: 50% 15. SpaceX has launched a man around the moon: 50% 16. SLS sends an Orion around the moon: 30% 17. Someone has landed a man on the moon: 1% 18. SpaceX has landed (not crashed) an object on Mars: 5% 19. At least one frequently-inhabited private space station in orbit: 30%
BIA 10-2474

BIA 10-2474 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 15, 2024 and May 15, 2024. The archive places it in contexts such as "In 2016, a Portuguese pharma company tested a FAAH inhibitor, BIA 10–2474". It most often appears alongside @the_megabase, A Pan-Species Welfare State, ACX Grantees.

Reference entry
BIA 10-2474
Mention count
1
Issue count
1
First seen
May 15, 2024
Last seen
May 15, 2024
May 15, 2024 · Original source
I can’t find anyone claiming to know exactly what went wrong with BIA 10-2474 (see here for what we do know). But the FDA released a statement a few months later saying they were confident that it was a particular feature of BIA 10-2474 and not a problem with FAAH inhibition in general. I don’t know their exact reasoning, but it might have to do with many other pharma companies trying different FAAH inhibitors with no problem. Far Out adds that the FAAH knockout mice also seem to do fine.
How safe will it be? In 2016, a Portuguese pharma company tested a FAAH inhibitor, BIA 10–2474, as a potential new painkiller. The trial was a disaster - out of 90 patients, one died and five were hospitalized. This almost never happens in clinical trials - pharma companies are usually good at eliminating potentially dangerous candidate drugs in vitro or in animal studies - so it was one of the biggest medical news stories of the year, and it chilled further research into FAAH.
BIIB080

BIIB080 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "tau antisense oligonucleotides such as BIIB080". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
BIIB080
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
(of course, this doesn’t mean tau is a bad target for therapy. I’m optimistic about tau antisense oligonucleotides such as BIIB080, which had a very promising phase 1b trial [116, 117] and is now in phase 2)
[117] A. L. Edwards et al., “Exploratory Tau Biomarker Results From a Multiple Ascending-Dose Study of BIIB080 in Alzheimer Disease: A Randomized Clinical Trial,” JAMA Neurology, vol. 80, no. 12, pp. 1344–1352, Dec. 2023, doi: 10.1001/jamaneurol.2023.3861.
bimagrumab

bimagrumab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2021 and December 20, 2021. The archive places it in contexts such as "promise of two new research chemicals, tirzepatide and bimagrumab". It most often appears alongside Cimbrian Seeresses, Conservatives, End Mass Incarceration.

Reference entry
bimagrumab
Mention count
1
Issue count
1
First seen
December 20, 2021
Last seen
December 20, 2021
December 20, 2021 · Original source
So for example, when Stephan talks about the promise of two new research chemicals, tirzepatide and bimagrumab, he’s able to punctuate his points with these graphs:
Binance Perfume

Binance Perfume is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 04, 2024 and April 04, 2024. The archive places it in contexts such as "Binance has launched “Binance Perfume” to “bring crypto[currency] closer to women”". It most often appears alongside Aaron Peskin, ACLU, AGI And The Efficient Market Hypothesis.

Reference entry
Binance Perfume
Mention count
1
Issue count
1
First seen
April 04, 2024
Last seen
April 04, 2024
April 04, 2024 · Original source
5: In honor of International Women’s Day, Binance has launched “Binance Perfume” to “bring crypto[currency] closer to women”.
Bing chatbot

Bing chatbot is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 01, 2023 and March 01, 2023. The archive places it in contexts such as "helped Microsoft launch the Bing chatbot in February". It most often appears alongside AGI, AI, Anthropic.

Reference entry
Bing chatbot
Mention count
1
Issue count
1
First seen
March 01, 2023
Last seen
March 01, 2023
March 01, 2023 · Original source
And so on . . . Meanwhile, in real life, OpenAI released ChatGPT in late November, helped Microsoft launch the Bing chatbot in February, and plans to announce GPT-4 in a few months. Nobody thinks society has even partially adapted to any of these, or that alignment researchers have done more than begin to study them. The only sense in which OpenAI supports gradualism is the sense in which they’re not doing lots of research in secret, then releasing it all at once. But there are lots of better plans than either doing that, or going full-speed-ahead. So what’s OpenAI thinking? I haven’t asked them and I don’t know for sure, but I’ve heard enough debates around this that I have some guesses about the kinds of arguments they’re working off of. I think the longer versions would go something like this: The Race Argument: Bigger, better AIs will make alignment research easier. At the limit, if no AIs exist at all, then you have to do armchair speculation about what a future AI will be like and how to control it; clearly your research will go faster and work better after AIs exist. But by the same token, studying early weak AIs will be less valuable than studying later, stronger AIs. In the 1970s, alignment researchers working on industrial robot arms wouldn’t have learned anything useful. Today, alignment researchers can study how to prevent language models from saying bad words, but they can’t study how to prevent AGIs from inventing superweapons, because there aren’t any AGIs that can do that. The researchers just have to hope some of the language model insights will carry over. So all else being equal, we would prefer alignment researchers get more time to work on the later, more dangerous AIs, not the earlier, boring ones.
Reading even further between the lines - at this point it’s total guesswork - OpenAI’s corporate partner Microsoft asked them for a cool AI. OpenAI assumed Microsoft was competent - they make Windows and stuff! - and gave them a rough draft of GPT-4. Microsoft was not competent, skipped fine-tuning and many other important steps which OpenAI would not have skipped, and released it as the Bing chatbot. Bing got in trouble for threatening users, which gave OpenAI a PR headache around safety. Some savvy alignment people chose this moment to approach them with their latest ideas (is it a coincidence that Holden Karnofsky published What AI Companies Can Do Today earlier that same week?), and OpenAI decided (for a mix of selfish and altruistic reasons) to get on board - hence this document.
Binyan Blocks

Binyan Blocks is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 29, 2024 and February 29, 2024. The archive places it in contexts such as "Judaism has Binyan Blocks". It most often appears alongside @BoyanSlat, @eigenrobot, @JackTindale.

Reference entry
Binyan Blocks
Mention count
1
Issue count
1
First seen
February 29, 2024
Last seen
February 29, 2024
February 29, 2024 · Original source
26: Did you know: lots of religions have their own version of LEGO, usually with sets depicting their mythology or temples. Islam has Muslim Blocks, Hinduism has Indic Bricks, and Judaism has Binyan Blocks. But my favorite is Mormonism with - wait for it - Brick’em Young (h/t @seanw_m)
Biosemi 32-channel EEG system

Biosemi 32-channel EEG system is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as ""and a clinical-grade Biosemi 32-channel EEG system"". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
bitly

bitly is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2022 and August 16, 2022. The archive places it in contexts such as "you can bring nice things like ... or follow a bitly link". It most often appears alongside ACX, Bay Area, Google Forms.

Reference entry
bitly
Mention count
1
Issue count
1
First seen
August 16, 2022
Last seen
August 16, 2022
August 16, 2022 · Original source
I also recommend collecting people’s names/emails — the best way to do this is to have people scan a QR code or follow a bitly link, to either fill out a Google Form or add themselves to an existing mailing list / group chat / etc. I used to recommend just pen and paper for this, but it turns out reading people’s handwriting is hard.
BitTorrent

BitTorrent is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 04, 2021 and July 04, 2021. The archive places it in contexts such as "inventor of BitTorrent". It most often appears alongside ACX, Ann Shulgin, Astralcodexten Com.

Reference entry
BitTorrent
Mention count
1
Issue count
1
First seen
July 04, 2021
Last seen
July 04, 2021
July 04, 2021 · Original source
1: There's another online ACX meetup next Sunday, special guest Bram Cohen, inventor of BitTorrent and the Chia cryptocurrency. Fill in this form to get an invite.
Blueprint

Blueprint is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 27, 2025 and February 27, 2025. The archive places it in contexts such as "Bryan Johnson’s Blueprint". It most often appears alongside /r/NootropicsDepot, @fae_dreams, @ObhishekSaha.

Reference entry
Blueprint
Mention count
1
Issue count
1
First seen
February 27, 2025
Last seen
February 27, 2025
February 27, 2025 · Original source
42: The supplement experts at /r/NootropicsDepot folks are not impressed with Bryan Johnson’s Blueprint:
Some blueprint products seem to be clearly out of spec, so Mr. Johnson probably doesn't really know what he's doing either. Not to mention that the lab they seem to be using, Certified Labs, used to be ABC testing which we know have botched a bunch of testing in the past. So bad in fact, that the FDA even intervened. It's always funny that quite a few brands with problematic products all seem to do their testing via Certified Labs/ABC testing. For example, look at where Gorilla Mind is testing their products, like Turkplex, which recently failed miserably in our testing. Bryan Johnson boasts about having all the money in the world, and that he's so super advanced blah blah blah, but he's testing with a seemingly sketchy lab even though there are a plethora of very well known labs doing great work, like Alkemist Labs for example. It really makes me wonder if these guys are knowingly selecting Certified Labs/ABC testing for a specific reason, or perhaps Certified Labs is very aggressive in marketing and if you are new in the industry, they may be the first lab you find? Odd, but could be a possibility.
Botox

Botox is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 23, 2021 and July 23, 2021. The archive places it in contexts such as "treat depression by using Botox to literally paralyze the facial muscles". It most often appears alongside Ace Attorney, Adam Smith, Amazon.

Reference entry
Botox
Mention count
1
Issue count
1
First seen
July 23, 2021
Last seen
July 23, 2021
July 23, 2021 · Original source
1: Previous research had suggested that you might be able to treat depression by using Botox to literally paralyze the facial muscles that make you frown. Two teams recently did meta-analyses of the research and came to different conclusions. Or rather, they came to the same conclusion - it has a really really big effect size - but they interpreted it differently: one team says it must be super great, another team said something must be wrong with the studies. Now the second team has responded to the first, in an article called (wait for it) Claims About The Effect Of Botulinum Toxin On Depression Should Raise Some Eyebrows.
brexanolone

brexanolone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "insanity of brexanolone IV". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
brexanolone
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
Progesterone is also really cheap (at least in comparison to the insanity of brexanolone IV).
the chemical difference between zuranolone and brexanolone is more substantial than the chemical difference between testosterone and estradiol. So... maybe it has the same effects, but maybe it's too far removed.
Brick’em Young

Brick’em Young is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 29, 2024 and February 29, 2024. The archive places it in contexts such as "Mormonism with - wait for it - Brick’em Young". It most often appears alongside @BoyanSlat, @eigenrobot, @JackTindale.

Reference entry
Brick’em Young
Mention count
1
Issue count
1
First seen
February 29, 2024
Last seen
February 29, 2024
February 29, 2024 · Original source
26: Did you know: lots of religions have their own version of LEGO, usually with sets depicting their mythology or temples. Islam has Muslim Blocks, Hinduism has Indic Bricks, and Judaism has Binyan Blocks. But my favorite is Mormonism with - wait for it - Brick’em Young (h/t @seanw_m)
BuffyCoin

BuffyCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 12, 2021 and February 12, 2021. The archive places it in contexts such as "Users receive BuffyCoins for slaying vampires". It most often appears alongside CAPTCHA, Catholic Church, ConTracked.

Reference entry
BuffyCoin
Mention count
1
Issue count
1
First seen
February 12, 2021
Last seen
February 12, 2021
February 12, 2021 · Original source
BuffyCoin: Users receive BuffyCoins for slaying vampires; the more dangerous the vampire, the greater the payout. Vampire-slaying is verified through...wait for it...proof-of-stake.
BurmaShave

BurmaShave is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 30, 2022 and May 30, 2022. The archive places it in contexts such as ""Think BurmaShave’s / a pricy scam?"". It most often appears alongside Ada Lovelace, Alexandra Elbakyan, Art Deco.

Reference entry
BurmaShave
Mention count
1
Issue count
1
First seen
May 30, 2022
Last seen
May 30, 2022
May 30, 2022 · Original source
Think BurmaShave’s / a pricy scam? Save on cash / With GilaWhamm!
buspirone

buspirone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "blocked by mediocre anti-anxiety medication buspirone". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
buspirone
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Silexan is a branded extract of lavender oil created by Wilmar Schwabe GmbH, a German pharma company. Nobody is sure about the mechanism of action, but it probably involves serotonin 1A receptors, the same receptors blocked by mediocre anti-anxiety medication buspirone and some of the newer antidepressants.
Butcher’s Son

Butcher’s Son is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 26, 2021 and February 26, 2021. The archive places it in contexts such as "Butcher’s Son has done it. They have solved plant-based bacon". It most often appears alongside American Chinese food, Bay Area, BBQ pork rice.

Reference entry
Butcher’s Son
Mention count
1
Issue count
1
First seen
February 26, 2021
Last seen
February 26, 2021
February 26, 2021 · Original source
The Butcher’s Son
The name The Butcher’s Son is based on the idea of the modern son of a butcher, who was raised eating animal products. When he grows up and opens his own business, he strives to create healthier and more sustainable options that still satisfy his cravings for the foods he grew up with.
The bacon was amazing. I have gotten some friends to try it, and they all agree it’s as good as real bacon. At least as good as real bacon. This is the best vegetarian bacon I have ever had. I would have expected bacon to be one of the hardest plant-based meats to get right, but Butcher’s Son has done it. They have solved plant-based bacon. There’s nowhere further to go from here.
C64

C64 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 27, 2023 and April 27, 2023. The archive places it in contexts such as "owning hardware C64 ->8088 ->286". It most often appears alongside 286, 8088, Adorno.

Reference entry
C64
Mention count
1
Issue count
1
First seen
April 27, 2023
Last seen
April 27, 2023
April 27, 2023 · Original source
...is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, G...
cagrilintide

cagrilintide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "amylin analogue cagrilintide with semaglutide". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
cagrilintide
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
Sixth, this post focuses on GLP-1 agonists, which makes sense, because those drugs are starting to have an impact today. But the Morgan Stanley report also notes that amylin analogue cagrilintide may be approved for weight loss as soon as 2025. This drug has a completely different mechanism than semaglutide, but likely offers similar weight loss benefits. The crazy thing is that the weight loss benefits stack. So Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide, and hopes to offer a ~30% average weight loss. This is roughly double what semaglutide offers, and is getting closer to bariatric surgery efficacy.
I most want to highlight the paragraph on the potential upcoming cagrilintide-semaglutide combination. Lots of commenters asked “okay, losing 15% body weight sounds good, but what if you need to lose more?” Probably the answer is “wait a few years for Cagrisema”.
Cagrisema

Cagrisema is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide"; "upcoming CagriSema combination". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Cagrisema
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
Sixth, this post focuses on GLP-1 agonists, which makes sense, because those drugs are starting to have an impact today. But the Morgan Stanley report also notes that amylin analogue cagrilintide may be approved for weight loss as soon as 2025. This drug has a completely different mechanism than semaglutide, but likely offers similar weight loss benefits. The crazy thing is that the weight loss benefits stack. So Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide, and hopes to offer a ~30% average weight loss. This is roughly double what semaglutide offers, and is getting closer to bariatric surgery efficacy.
I most want to highlight the paragraph on the potential upcoming cagrilintide-semaglutide combination. Lots of commenters asked “okay, losing 15% body weight sounds good, but what if you need to lose more?” Probably the answer is “wait a few years for Cagrisema”.
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Camel

Camel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 31, 2025 and July 31, 2025. The archive places it in contexts such as "This is like Marlboro attacking Camel on the grounds that cigarettes are addictive and should be banned". It most often appears alongside 23andMe, 23andme, Alex Young.

Reference entry
Camel
Mention count
1
Issue count
1
First seen
July 31, 2025
Last seen
July 31, 2025
July 31, 2025 · Original source
…which included a section on how Orchid is a polygenic selection company, and polygenic selection companies are inherently “sketchy” and “honestly should be illegal”. But Nucleus is also a polygenic selection company! This is like Marlboro attacking Camel on the grounds that cigarettes are addictive and should be banned! Obviously something went wrong here - my guess is AI - and it’s a really bad look, especially when these scientific issues are so hard to litigate, and so many of us will have to go off gestalt impressions of corporate culture. Nucleus states that they validate their models internally and intend to make their results public soon. A Foothill Of The Future It’s hard not to love this technology. Lots of people (and the aforementioned professional organizations) manage anyway, but it’s hard. If this were a single-use medical treatment, delivered by a doctor after someone got the relevant condition, it would be one of the biggest advances of the decade - imagine a drug that cures 10 - 40%17 of breast cancers with no side effects! But in fact, it works for breast cancer, and schizophrenia, and heart attacks, and approximately everything else. The only things comparable are antibiotics and GLP-1RAs. And then there’s the IQ effects. Even after studying the literature, people have wildly different opinions about the importance of IQ. One of the most important debates is to what degree IQ differences are a cause of poverty, a consequence of poverty, or both. I lean towards both - a country with limited access to schools and medical care will have low average IQ, but as a consequence it probably won’t become the next big semiconductor hub. This technology could close half the IQ gap between poor and middle-income countries, or between middle-income and rich. Or it could give rich countries average IQs that have never been seen before, and let us see what kind of O-ring technologies (and new forms of social cooperation) lie just beyond the frontier. (this is the nice quantifiable argument in favor of IQ enhancement, but I find myself more convinced by fuzzier things - how much is it worth to be able to enjoy great art and literature? To fully comprehend what we know of nature, and be able to fully appreciate the mystery of the rest? To have a sense of why society works the way it does, instead of feeling like you’re being blown back and forth by institutions you don’t really understand? Amateur psychoanalysts like to say that the only people who care about IQ are those looking for an excuse to boast about how high their own is, but my experience is the opposite: I care about IQ because I bang up against the limits of my own a thousand times a day, and I hate it. I fantasize about ways to make my children smarter than I am for the same reason a dog confined in a tiny crate might fantasize about getting her puppies adopted out to a nice house with a big grassy yard.) My biggest qualm is that it might not matter. This is such a tiny foothill, flanking such a vast and foreboding range of mountains, that it might be a mistake to care about it at all. Selecting the best of five or ten embryos is not a very effective way to get the genes you want. There are things in the pipeline that will make this look like Hippocrates draining black bile. By the time the first polygenically selected children are adults, they’ll be old news. And then there’s AI. The average age at diagnosis for Type II diabetes is 45 years. Will there still be people growing gradually older and getting Type II diabetes and taking insulin injections in 2070? If not, what are we even doing here? Many people in the transhumanist community are still bullish on this technology. They think - well, there’s still an outside chance that something comes up and AGI takes another few decades. If we can enhance humans to be smarter, healthier, and more determined by the time it arrives, maybe we’ll have a better chance. Or maybe, if there’s a positive optimistic vision of a human-based high-tech future, people will be more willing to delay AI in the first place. I like this argument, but I also think it’s worth stepping back. What’s the point of anything? Why have kids at all in a world that’s changing this fast? Why save for the future? At some point your answer has to be romantic and aesthetic - it’s never been clear whether anything you do matters in any ultimate sense, but you’ve got to act as if it does and hope for the best. From that perspective, this is the most romantic technology of all. You’re not just giving a better life to your kids. Genes travel from generation to generation; you’re giving a better life your grandkids, your great-grandkids and so on to the point 1.77*log₂(population) generations from now when you are the ancestor of everybody and nobody. Somebody in Macaronesia in 3525 AD will avoid getting breast cancer because of you (if there is still cancer; if there are still breasts). Some combination of reasonable cost-benefit analysis and romantic/aesthetic commitments makes me want to have children despite the uncertainty, and the same combination made me sign up to use this technology despite the same. More later on how that’s going. 1I’m slightly mixing up two different things here - Down Syndrome can be detected with an aneuploidy test, but cystic fibrosis takes a more involved PGT-M test. 2There are two separate questions here. First, how much would diabetes risk decline if you selected the embryo with the lowest risk for diabetes - something you have no reason to do, since you have no reason to privilege diabetes risk over risk of any other disease? Second, how much would diabetes risk go down if you selected the embryo with the lowest health risk overall? Genomic Prediction’s their risk calculator calculator shows, seemingly paradoxically, that you get -38% relative risk by selecting against diabetes alone, but -41% relative risk by selecting against everything at once. Over email, they stand by this surprising result, saying that “for a couple of diseases (type II diabetes and CAD), the EHS actually accomplishes a larger risk reduction than the individual predictors. The explanation is that the EHS takes into account multiple PRS of diseases with high comorbidity”. See eg Figure 3 here: …and the section of the post called “Antagonistic Pleiotropy” for more. However, this paradoxical benefit is only true for a few conditions like diabetes - for everything else, selecting on health index does better than you would naively think, but still does not decrease the risk of a given condition as much as selecting against that condition directly. 3That is, new mutations in that particular baby, as opposed to older mutations already present in the parents. 4Conflicts of interest: I have used Orchid’s and Herasight’s products on my own embryos (not the ones used to conceive my existing kids, but for a potential third child), employees of Genomic Prediction and Herasight have been extremely helpful in contributing expertise to ACX posts on genetics, and I might invest in this field at some point (though haven’t done so yet). This post started as Herasight asking me to write about their white paper, then spiraled out of control. There were some unexpected time pressures and the result is that I didn’t get a chance to run everything in Herasight’s white paper by their competitors as thoroughly as I would like. Although I talked to representatives of all four companies profiled here, I feel like this probably reflects Herasight’s perspective better than other companies’, and that this is a major flaw. If other companies have responses, I’ll publish them. Thanks to all companies involved for their assistance on this article. Finally, I am favorably disposed toward Herasight because of how I learned about them: a professor named Jonathan Anomaly got cancelled from Penn for being too gung-ho about genetic enhancement, and used his newfound freedom to join a very-early-stage Herasight, raise their ambitions, and sell everyone (including me) on the idea. I grew up on a diet of books and movies about mad scientists, and I’m a sucker for a story about a guy named Doctor Anomaly pursuing revenge against the small-minded fools who destroyed his career by creating a race of superbabies. 5The version of the tool I looked at said 5.9 points for five embryos, up to 9 points for twenty embryos. The version of the tool on their current said says 5.3 - 9, so they might have recalculated after I finalized this article. 6Used in quotation marks because these scores were fine for the predictive tasks they were applied for - they just weren’t finding genes that directly caused the outcome of interest. 7Conflict of interest notice: this table was originally unadjusted. A representative of Herasight claimed that this was unfair, because each company used slightly different reporting conventions, and offered to correct for this in a neutral way. I retraced their reasoning, confirmed that the correction did not especially benefit Herasight at the expense of other companies, and accepted the correction. The original unadjusted table is below: Herasight was insufficiently comfortable with Nucleus’ methodology to even be willing to posit a corrected value, so I left their self-reported value in gray. 8Zagorsky (2007) says an extra IQ point means $234-$616/year in higher salary. The midpoint of $425 equals $670 in today’s dollars; assuming a forty-year career, Nucleus’ +1 point estimate is worth $26,800 (vs. $9,249 Nucleus cost) and Herasight’s +6 point estimate is worth $160,800 (vs. $53,250 Herasight cost). 9As part of researching this article, I asked all four major companies about their within-family validation strategies. Here are some details: Genomic Prediction discusses their strategy in this paper. The results are complicated to interpret - the within-family numbers often have such wide error bars that they overlap with both the across-family numbers and with zero - but looking qualitatively it seems like most scores on average lose about 25% of their risk reduction ability (though averages might not be the right way to do this, and some might be much more affected than others). Their website reports unadjusted, not within-family validated numbers; GP says they say this clearly on their site (which is true), Herasight counters that they still present their numbers as applicable to embryo selection (which is also true). To get the most applicable-to-embryo-selection numbers, you might want to adjust GP’s stated numbers down somewhat; it’s hard to say exactly how much, but maybe 20 - 25%?
Campbell’s soup cans

Campbell’s soup cans is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 08, 2025 and January 08, 2025. The archive places it in contexts such as "like Cambpell’s soup cans". It most often appears alongside #DogeCoin, Alex Tabarrok, Arnold Kling.

Reference entry
Campbell’s soup cans
Mention count
1
Issue count
1
First seen
January 08, 2025
Last seen
January 08, 2025
January 08, 2025 · Original source
In art and architecture, the drive to be “in touch” took the form of pop art and postmodern architecture, where artists took the materials of normal public life (like Cambpell’s soup cans) and transformed it in some kind of complicated way. The average member of the public might think “Campbell soup! That artist is in touch with my everyday existence!” while also being baffled by layers of ironic reference and artistic flourishes outside his puny little brain’s ability to comprehend. A+ instant classic.
Cannabets

Cannabets is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "the most exciting product we’ve seen since Cannabets, the combination marijuana delivery and digital casino app". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
Cannabets
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
“And that’s the beauty of social selection! You don’t have to like it. My backers at Andreessen Horowitz told me, and I quote, that ‘This is the most exciting product we’ve seen since Cannabets, the combination marijuana delivery and digital casino app that lets you fund your pot orders by gambling on how long it takes you to get addicted.’ And the more often you disagree with me, the more likely I am to go to parties with them instead of you.”
Capecitabine

Capecitabine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2021 and February 05, 2021. The archive places it in contexts such as "Capecitabine ("Xeloda") can sometimes make you lose your fingerprints". It most often appears alongside Adderall, Anthony Fauci, aspirin.

Reference entry
Capecitabine
Mention count
1
Issue count
1
First seen
February 05, 2021
Last seen
February 05, 2021
February 05, 2021 · Original source
"You listed three major side effects of this drug, but I got a side effect that isn't on your list. Maybe you should add it in." All drugs have an infinite number of possible side effects. One in a zillion people who use Naproxen ("Aleve") becomes red-green colorblind. Capecitabine ("Xeloda") can sometimes make you lose your fingerprints, which sucks if your computer has biometric security. If listed all side effects of anything, we would be here all day. Still, I get nervous when I get emails like this. What if an interior designer takes Aleve, loses their color vision, and it's my fault for not warning them?
Cap’n McCain's

Cap’n McCain's is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "they had to give out Cap’n McCain's for free". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Cap’n McCain's
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Both designers who graduated from the prestigious Rhode Island School of Design, the pair created fictitious cereals called “Obama O's, the Cereal of Change,” and “Cap’n McCain's, a Maverick in Every Box.” They designed the box artwork themselves and convinced a student at UC Berkeley to print 500 units of each box on the cheap. The boxes were delivered as flat rectangles that had to be cut and assembled by hand.
The founders sent boxes to hundreds of the most well-known tech bloggers, hoping that they would proudly display them on their desks and that they, or their colleagues, would eventually write their story. Shortly thereafter, they started selling the political cereal at $40 per box. The Obama O's sold like hot cakes, so much so that they had to give out Cap’n McCain's for free with each purchase.
Cap’n McCain's, a Maverick in Every Box

Cap’n McCain's, a Maverick in Every Box is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "fictitious cereals called ... “Cap’n McCain's, a Maverick in Every Box”". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Both designers who graduated from the prestigious Rhode Island School of Design, the pair created fictitious cereals called “Obama O's, the Cereal of Change,” and “Cap’n McCain's, a Maverick in Every Box.” They designed the box artwork themselves and convinced a student at UC Berkeley to print 500 units of each box on the cheap. The boxes were delivered as flat rectangles that had to be cut and assembled by hand.
The founders sent boxes to hundreds of the most well-known tech bloggers, hoping that they would proudly display them on their desks and that they, or their colleagues, would eventually write their story. Shortly thereafter, they started selling the political cereal at $40 per box. The Obama O's sold like hot cakes, so much so that they had to give out Cap’n McCain's for free with each purchase.
Carolina Reaper

Carolina Reaper is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 15, 2024 and May 15, 2024. The archive places it in contexts such as "a video of him eating Carolina Reaper peppers". It most often appears alongside @the_megabase, A Pan-Species Welfare State, ACX Grantees.

Reference entry
Carolina Reaper
Mention count
1
Issue count
1
First seen
May 15, 2024
Last seen
May 15, 2024
May 15, 2024 · Original source
Our physical differences are easy to notice. Everyone knows that some people are black, some white, some Asian or Hispanic. Everyone knows that some babies are born with one arm, or three eyes, or webbed fingers. But nobody knows how many mental mutants walk among us. Here’s a Reddit post by a guy who says spicy food has no effect on him, complete with a video of him eating Carolina Reaper peppers and looking kind of bored. Here are some pictures by a woman who can see 100x more colors than normal.
Maybe you could try eating a couple of Carolina Reaper peppers - the ones from that YouTube video earlier. Maybe eat a whole handful at once. Maybe rub them in your eyes for good measure. Then, when you’re rolling on the floor screaming and cursing your past self for making this decision, think of the people who live with chronic pain conditions and feel this way every day. Think of the wounded soldiers who lie on the battlefield screaming for water until they finally expire, or the animals who get eaten from the inside by parasites, or the mentally ill people stuck in padded rooms so they don’t try to kill themselves to escape the pain, or the chickens in factory farms that have their beaks cut off and can never move and are starved for weeks at a time and sometimes drown in their own waste. Can you get have a mystical conversion experience from eating enough peppers? I don’t know, but I feel like this is the kind of vision that could make someone a Pearcian.
Casinu Inu

Casinu Inu is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2024 and February 20, 2024. The archive places it in contexts such as "the "Casinu Inu" ERC20 token". It most often appears alongside 2024 presidential election, Aella, AI.

Reference entry
Casinu Inu
Mention count
1
Issue count
1
First seen
February 20, 2024
Last seen
February 20, 2024
  • 24 February 20, 2024
February 20, 2024 · Original source
Is 0x1b54....98c3 actually the address of the "Casinu Inu" ERC20 token?
imdevimab

casirivimab/imdevimab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 23, 2021 and November 23, 2021. The archive places it in contexts such as "even those approved by western health authorities, including casirivimab/imdevimab"; "including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid". It most often appears alongside 1/6 insurrectionists, Ahmed, Alabama.

Reference entry
imdevimab
Mention count
1
Issue count
1
First seen
November 23, 2021
Last seen
November 23, 2021
November 23, 2021 · Original source
Author appears to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid.
The steps required to accept the no-significant-effect outcome are extreme — one needs to find a reason to exclude most of the studies, disregard the strong treatment-delay response relationship, and disregard all prophylaxis studies. Even after this, the result is still positive, just not statistically signficant. This does not support a negative recommendation. Widely accepted and effective (subject to dependence on viral variants) treatments like casirivimab/imdevimab, bamlanivimab, and sotrovimab were all approved without statistically significant mortality benefits.
First, the claim that I "[appear] to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid." They suggest I am turning my readers away from other treatments including ones that are already standard of care in western health systems.
Celexa

Celexa is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 31, 2021 and March 31, 2021. The archive places it in contexts such as "Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram)"; "The most effective dose of every SSRI would be: Celexa: 30 mg". It most often appears alongside ASRI, Cipriani, citalopram.

Reference entry
Celexa
Mention count
1
Issue count
1
First seen
March 31, 2021
Last seen
March 31, 2021
March 31, 2021 · Original source
What is the right dose of Lexapro (escitalopram)?
Because Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram). Sometime around 2011, the FDA freaked out that high doses of citalopram might cause a deadly heart condition called torsade de pointes, and lowered the maximum dose to prevent this. Since then it's been pretty conclusively shown that the FDA was mostly wrong about this and kind of bungled the whole process. But they forgot to ever unbungle it, so citalopram still has a lower maximum dose than every other antidepressant. When escitalopram was invented, it inherited its parent chemical's unusually-low maximum dose, and remains at that level today [edit: I got the timing messed up, see here]
Now that we know the heart risk was overblown, should we increase the maximum dose to something closer to other SSRIs? Maybe not. Right now, escitalopram keeps showing up in studies and head-to-head comparisons as the most effective SSRI.
cell phones

cell phones is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 22, 2023 and February 22, 2023. The archive places it in contexts such as "exposed to electromagnetic fields (like from cell phones)". It most often appears alongside Africa, Agin, American.

Reference entry
cell phones
Mention count
1
Issue count
1
First seen
February 22, 2023
Last seen
February 22, 2023
February 22, 2023 · Original source
This image (source) of a witch stealing a man’s penis, with a box of previously-stolen penises to her right accompanies the 1411 poem “Flowers Of Virtue” in its 1486 edition. Malleus Maleficarum was published in 1486, so if the original text of Flowers Of Virtue contained the incident this picture refers to, it would predate Malleus. But the original text is written in poetic medieval German and I can’t find a good translation. When I wrote my review of the Malleus, people were surprised at the penis-stealing witch chapters. Yet nothing could possibly be less surprising; the penis-stealing witches are timeless and omnipresent. When commenters continued to doubt, I promised them this review of Frank Bures’ Geography Of Madness. II. Frank Bures is a journalist. In 2001, he came across an unusual BBC article: a mob had killed twelve people in Nigeria, believing them to be penis-stealing witches. A few months later, a similar article: five people, Benin. He tried to pitch a story about the phenomenon to his editor, who “said he couldn’t pay me to fly to Nigeria and find essentially . . . nothing”. For some reason - and this is the point at which I start to worry about narrator reliability - Bures became obsessed with this. He couldn’t get it out of his mind. He started scraping together money to visit Africa on his own, story be damned: Nigeria gnawed at me. I knew that it was a terrible time to leave. I knew that [my wife] Bridgit, newly pregnant, wouldn’t want me to go. But I also knew that I had to, and that if I didn’t it would be a lifelong regret. . . three months later, I was the lone tourist on a plane full of Nigerians descending to Lagos. Africa is a relative newcomer to penis-stealing witches: The first recorded incident of penis theft in Africa I could find took place in Sudan in the 1960s. But in the mid- to late seventies in Nigeria, there were waves of well-documented cases. One of these happened in the northern city of Kaduna, where a psychiatrist named Dr. Sunday Ilechukwu was working in his office when a policeman arrived, escorting two men. One of them said he needed a medical assessment: He had accused the other of making his penis disappear. As with [a previously discussed incident], this had caused a disturbance in the street. During Ilechukwu’s examination, he later recounted, the victim stared straight ahead while the doctor examined his penis and pronounced him normal. “Exclaiming,” Ilechukwu wrote in the Transcultural Psychiatric Review, “the patient looked down at his groin for the first time, suggesting that the genitals had just reappeared.” According to Ilechukwu, this was part of an epidemic of magical penis theft that swept through Nigeria between 1975 and 1977. “Men could be seen in the streets of Lagos holding on to their genitalia either openly or discreetly with their hand in their pockets,” Ilechukwu wrote. “Women were also seen holding on to their breasts directly or discreetly, by crossing the hands across the chest . . . Vigilance and anticipatory aggression were thought to be good prophylaxes. This led to further breakdown of law and order.” During an incident, the victim would yell: “Thief! My genitals are gone!” Immediately, a culprit would be identified, apprehended by a crowd, and often killed. …but it’s been making up for lost time. Bures was able to find and interview one previous penis theft victim, plus the friend of another. Both described similar stories: someone had bumped up against them under weird circumstances, they immediately noticed their penis was much smaller than usual, they called out the culprit, and - apparently because the witch involved didn’t want to get in trouble - their penis was restored. Whatever weird itch this topic had given Bures, this didn’t satisfy him. He writes, very lucidly, about a desire to get closer to “the story”. He started bumping up against random Nigerians in suspicious ways, hoping one of them would accuse him of stealing their penis. Bures was an obvious foreigner, and a these panics often resulted in the suspected penis-stealer getting lynched, so this was a crazy thing to do. He could easily have died. Instead, everyone politely ignored him, nothing happened, and a slightly-disappointed Bures flew back to his poor family and abandoned his weird obsession. III. …for four years. After that the bug bit him again and he flew to Asia, long a center of penis-stealing witch activity. There are nature documentaries on lions, dolphins, even dinosaurs. They all share a common pattern: you talk about your subject’s habitat, their diet, their behaviors. The Asian half of The Geography Of Madness has the feel of a nature documentary on penis-stealing witches. And the last beat of every nature documentary has to be: this majestic creature, which once roamed from one end of the region to the other, is now endangered, threatened by increasing globalization and industrial activity. This is true for the witches also. Bures’ time in Hong Kong was a bust. There was a penis theft panic there forty years earlier, and he was able to interview some of the doctors who treated it. But they all said that was long ago. Now everybody is Westernized and has Western fears like vaccine injury or structural racism. They get Western mental disorders like depression and anorexia. The idea of witches stealing their penises seems as risible to them as it probably does to you. Singapore was also a bust. Bures had hoped it wouldn’t be, because it’s full of Malaysians, and Malaysia holds a special place in history as the spot where penis-stealing witches first made contact with Western science. The Malaysian word for the condition is koro (it means “head of a turtle”, based on an analogy to the penis retracting into the body the same way a turtle’s head retracts into its shell), and it is by this name that the condition gets listed in the DSM and the rest of the medical literature. Neither I nor Bures was able to find many ethnic Malays worrying about koro; most of the activity seems to be from Malaysian-Chinese. The Chinese definitely worry about it, attributing it to a wide variety of causes including poisoning, yin-yang imbalance, and - yes - witches. But Bures found nothing among any ethnicity. Once again, all the doctors said it used to be common, but disappeared as the city industrialized and adopted Western ways. Guangzhou was also a bust. The doctors said the same thing - in the old days, there would be huge epidemics of koro, social contagions that would impact hundreds of people at once. Now only a few superstitious rural people still believed. One traditional healer said he saw “three or four” cases a year. All the educated people had moved on. I once saw a nature documentary on Tasmanian tigers. Most people believe these have been extinct since 1930. Still, there are occasional unconfirmed sightings, especially in a remote area called Cape York, and every so often some scientists trudge off to Cape York with traps and cameras in the hopes of getting lucky. Bures decides end his own nature documentary with an expedition to the Cape York of the penis-stealing witches. This is a remote island village in China called Lin’gao, where in 1984: . . . rumors spread of a fox ghost - sometimes disguised an old woman roaming the land—collecting penises in covered baskets she carried on a shoulder pole. When two young men approached her and told her to uncover the baskets, they looked inside, saw that the baskets were filled with penises and died instantly of fright. Panic about koro would hit a village and last three to four days. When residents heard about a case in a neighboring village, the panic would subside, since that meant the ghost had moved on. The attacks slowly made their way around the island. The ghost struck at night, when villagers were sleeping. A chill would creep into the room, and suddenly the victim would feel his penis shrinking inward. He would grab it and run outside for help. A twenty-eight-year-old office worker was at home one night when: > “ . . . he heard a gong being beaten and the terrifying noises made by people who were panicking in a nearby neighborhood. He suddenly became anxious and experienced the sensation that his penis was shrinking. He was seized with panic and shouted loudly for help. Several men in the neighborhood rushed in and tried to rescue him by forcefully pulling his penis and making loud sounds to chase away the evil ghost that was thought to be affecting him.” Neighbors and family members were enlisted in rescue operations. Victims were beaten with sandals and slippers while the middle finger of their left had was squeezed, so that the ghost could exit the body there. The epidemic engulfed the island, with the exception of the Li and Miao minorities, who seemed to be immune to such fears. Researchers estimated that between 2,000 and 5,000 people were affected, but that “no one died from genital retraction.” One baby, however, did die when his mother tried to feed him pepper juice, and a girl was beaten to death during a two-hour exorcism. “Numerous men suffered injuries to their penises as a result of ‘rescuing’ actions.” Iron pins were sometimes inserted through the nipples of women to prevent retraction, which caused infections as well. This was, as far as anyone knows, the last great koro epidemic in Asia. Bures had a terrible time getting to Lin’gao. He had equal trouble getting an interpreter; the natives spoke a language called Be, very distantly related to Thai but not at all to regular Chinese. Finally he found someone who was able to contact a local shaman. Like any good doctor, the shaman referred him to a specialist - in this case, the designated anti-ghost shaman, who lived in a different village. He spent most of his time off on various ghost-fighting missions, but eventually Bures and his team were able to track him down. I want you to picture the scene. An American journalist has been traveling the world in search of a dying variety of witchcraft. Now he’s reached the end of the line, the wildest and most primitive region of China. With great difficulty, he has procured an interpreter. Together, they consult a shaman, who sends them on a quest to find a second, wiser shaman who specializes in ghosts. After many trials and tribulations, he reaches the second, wiser, ghost-specialist shaman, who invites him into his home, filled with strange charms and magical images. “Tell me your question,” says the shaman. And Bures asks: “What do you know about penis-stealing witches?” . . . and the shaman answers: “Haha, no one believes in that stuff anymore.” IV. So as a nature documentary, The Geography of Madness is kind of a bust. Still, Bures rescues it with some great analysis of culture-bound mental illness. A culture-bound mental illness is one that only affects people who know about it, and especially people who believe in it. Often it doesn’t make sense from a scientific point of view (there’s no such thing as witches, and the penis can’t retract into the body). It sometimes spreads contagiously: someone gets a first case, the rest of the village panics, and now everyone knows about it / believes in it / is thinking about it, and so many other people get it too. Different cultures have their own set of culture-bound illnesses. Sometimes there are commonalities - many cultures have something something penis something witches - but the details vary, and a victim almost always gets a case that matches the way their own culture understands it. THESE PEOPLE ARE NOT MAKING IT UP. I cannot stress this enough. There are plenty of examples of people driving metal objects through their penis in order to pull it out of their body or prevent the witches from getting it or something like that. There is no amount of commitment to the bit which will make people drive metal objects through their penis. People have died from these conditions - not the illness itself, which is fake, but from wasting away worrying about it, or taking dangerous sham treatments, or getting into fights with people they think caused it. If you think of it as “their unconscious mind must be doing something like making it up, but their conscious mind believes it 100%”, you will be closer to the truth, though there are various reasons I don’t like that framing. In Rajasthan, India, people come to the hospital with gilahari (lizard) syndrome. Patients say a lizard-like mass, sometimes visible as a skin swelling, is crawling around the body. They express terror that it will reach their airway and suffocate them. Japanese people may contract jikoshu-kyofu, a debilitating fear that they have terrible body odor. No amount of reassurances by friends and psychiatrists can convince these people that they smell normal, nor will any number of deodorants or perfumes make them comfortable. The French suffer from bouffée délirante, where a perfectly healthy person suddenly becomes completely psychotic, with well-formed hallucinations and delusions - then recovers just as suddenly, sometimes over hours or days. This is not how psychosis works anywhere except France and a few former French colonies. Traditional Chinese medicine monitors the balance between yin and yang. The male orgasm can deplete yang, and sure enough in China (but nowhere else) some men suffer traditional symptoms of yang depletion after they orgasm. “The symptoms can last weeks to months after a single orgasm, [and include] chills, dizziness, [and] backache”. The phrase “run amok” comes from Malaysia, where it referred to a specific phenomenon: some person who had been unhappy for a long time would suddenly snap, kill a bunch of people, then say they had no memory of doing it. Malaysian culture totally rolls with this and doesn’t hold it against them; the unhappiness is a risk factor for possession by a tiger spirit, which commits the killings. Although Malays have been doing this since at least the 1700s, there are some fascinating parallels with modern US mass shootings that suggest the damn tiger spirits have finally made it to the US common psychological origins. I have seen exactly one demonic possession case in my ten years as a psychiatrist. The man fell to the ground, mouth foaming, chanting strange syllables and the names of Biblical demons. My attending doctor at the time - one of those people who somehow manages to be an expert in everything - was an expert in demonic possession, and told us that he was in no way psychotic, antipsychotics wouldn’t help him (except insofar as they help everyone by decreasing all behaviors), and he needed to “work through his issues”. The patient was uncooperative - he was only visiting MDs because the local bishop wouldn’t call in an exorcist until he got a psych exam - and eventually left against medical advice. After going down the list, Bures asks the correct next question: how do we know whether or not our own mental illnesses are just as culture-bound as the Japanese or Malaysians’? Cultures that believe in witches have witch-related culture-bound illnesses; cultures that believe in demons have demon-related ones. We believe in science, so we should expect sciencey-sounding culture-bound illnesses, and these might be hard to tell apart from other, more physical conditions. So how suspicious should we be, and of what? Certainly we have some culture-bound mental illnesses. Electromagnetic hypersensitivity is a condition where some people supposedly become very sick when exposed to electromagnetic fields (like from cell phones). This sounds very scientific and makes perfect sense according to our culture, but researchers have found that placebo electrical devices make them exactly as sick as real ones, and that devices they don’t know about don’t make them sick at all. These people’s pain is real, and their lives are very difficult (although a few have found refuge in the National Radio Quiet Zone, an area in Virginia where the government enforces a ban on electromagnetic transmissions for secret military reasons). But their condition only afflicts them because they believe in it, much like with koro. Fine, everyone knows that one’s not real. What about DSM-style mental disorders, the stuff everyone’s supposed to believe in? Are those culture-bound? Unfortunately, I think Bures kind of flubs this section. He decides to focus on PMS (premenstrual syndrome), which is officially included in the DSM as PMDD (premenstrual dysphoric disorder). After discussing the history of hysteria, he writes that: Today, hysteria is never diagnosed, except by unwise husbands. In 1931, however, an American gynecologist named Robert Frank revived the idea in a new guise. He published an article titled, “The hormonal causes of premenstrual tension.” Frank described symptoms that occurred in the week before menstruation: irritability, bloating, fatigue, depression, attacks of pain, nervousness, restlessness, and the impulse for “foolish and ill considered actions,” due to ovarian activity. Again, the cause was the uterus. Then in 1953, British physician Katharina Dalton elaborated on this, arguing the condition came from fluctuation of estrogen and progesterone. She called it Premenstrual Syndrome, and soon symptoms grew to include: anxiety, sadness, moodiness, constipation or diarrhea, feeling out of control, insomnia, food cravings, increased sex drive, anger, arguments with family or friends, poor judgment, lack of physical coordination, decreased efficiency, increased personal strength or power, feelings of connection to nature or to other women, seizures, convulsions, asthma attacks, not to mention flare ups in asthma, allergies, sinusitis, anxiety disorders, irritable bowel syndrome, migraines, and multiple sclerosis. If any of these symptoms occurred in the second half of the menstrual cycle, one had PMS. Estimates of the number of women afflicted ranged from 5 percent to 95 percent. In the 1980s, three women in the UK were tried for arson, assault and manslaughter. The three all claimed they had diminished responsibility due to PMS, and got reduced sentences on the condition that they underwent hormone treatment. After that, according to one study, American women flooded doctors with requests for help with their PMS. “Popular groups like PMS Action were founded to promote recognition and treatment of PMS by medical professionals. Private PMS clinics began to appear in the USA, modeled after those in the UK, and progesterone therapy was enthusiastically adopted, much to the chagrin of many gynaecologists who viewed its use as ‘unscientific’ and ‘commercial’, not to mention unlicensed." Based on all this, the 1987 version of the DSM-III included a new category: Late Luteal Phase Disorder (luteal refers to progesterone). It was proposed as a topic for further research, but despite the absence of such research, it was included in the 1994 edition of the DSM-IV under the name Premenstrual Dysmorphic Disorder, or PMDD.96 In 2013, in the DSM-5, it was given its own category as a full-fledged mental illness. Yet neither PMS nor PMDD occur in most cultures. There are no biomarkers to measure them by. No conclusive correlation has ever been found between estrogen or progesterone levels and PMS. As one study noted, “the more time that women of ethnic minorities spend living in the United States, the more likely they are to report PMDD. Thus, if we are to accept PMDD as a reified medical disorder, then we must also accept exposure to U.S. culture as a risk factor for contracting PMDD.” If it is a syndrome at all, it’s a cultural one. I asked my wife what she thought of this, and she told me: The day before her first-ever period, as a teenager, when she had never really thought about PMS, she felt exceptionally weird, emotional, and generally off, to the point where it seemed to demand an explanation. Then she had her first-ever period, and retroactively explains it as PMS.
Cessna

Cessna is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 09, 2023 and August 09, 2023. The archive places it in contexts such as "Cessna in 1959". It most often appears alongside @data_depot, @StefanFSchubert, AI Snake Oil blog.

Reference entry
Cessna
Mention count
1
Issue count
1
First seen
August 09, 2023
Last seen
August 09, 2023
August 09, 2023 · Original source
8: Zach Stein-Perlman’s favorite AI governance research this year. 9: The Chichijima incident was notable as a time when George H. W. Bush almost got eaten by cannibals. During WWII, nine American pilots were shot down over an island commanded by a crazy Japanese officer who ate his enemies' livers. Eight were captured and killed (and four of those were eaten), and Bush alone fled and survived. 10: El Salvador’s murder crackdown claims results of 90% decrease in homicides, 44% decrease in emigration to US, and 90% approval rating for president Nayyib Bukele (h/t Richard Hanania). 11: In an earlier set of comments, I ignorantly repeated a claim that Mother Teresa denied her patients painkillers because she thought suffering brought people closer to God. A commenter corrected me: painkillers were just generally in short supply in India during her era (more discussion here). 12: The record for longest time a plane has spent in the air without landing is 64 days, achieved by a Cessna in 1959. You can read the full story here, but the basic setup looked like this: 13: Fact check: was Elvis Jewish? Snopes says yes, but I’m more convinced by this argument for no. [update: commenter TheGenealogian agrees no] 14: Is GPT-4 getting worse? This isn’t absurd; some people claim OpenAI has simplified the model to cut costs (though OpenAI denies this). Matei Zaharia argues yes, but I’m more convinced by the AI Snake Oil blog’s argument for no (h/t Stuart Ritchie). 15: Vox has a good piece about AI company Anthropic. I would quibble that they’re not the only safety-focused or EA-affiliated org, and we have yet to see how truly safety-focused or altruistic any AI company can be while continuing to be an AI company. But granting that it’s all a matter of degree, I agree the degree seems pretty high for them. And NYT also has an Anthropic article. 16: Eliezer bets $150,000 to $1,000 against UFOs being aliens, and gives the same argument I would - it’s unlikely that any civilization advanced enough to travel through space would still be primitive enough to use macroscopic, biologically-piloted craft that sometimes crash. 17: More nails in the coffin of growth mindset. “When examining the highest-quality evidence (6 studies, N = 13,571), the effect was nonsignificant: d = 0.02, 95% CI = [−0.06, 0.10]. We conclude that apparent effects of growth mindset interventions on academic achievement are likely attributable to inadequate study design, reporting flaws, and bias.” I think the older, very-high-effect-size studies were clearly terrible, but I’d still like to look further into the newer, small-but-significant-effect-size-that-makes-a-difference-across-large-groups studies and how they went wrong. 18: Previous work showed that after adjusting for selection bias, “what college you go to doesn’t matter” for average earnings. I was always skeptical of this - are all those rich people sending their kids to Ivies for no reason? Now Chetty, Deming, and Friedman find that: Attending an Ivy-Plus college instead of the average highly selective public flagship institution increases students’ chances of reaching the top 1% of the earnings distribution by 60%, nearly doubles their chances of attending an elite graduate school, and triples their chances of working at a prestigious firm. Ivy-Plus colleges have much smaller causal effects on average earnings, reconciling our findings with prior work. One of the authors, David Deming, has a Substack here where he explains the study in more depth. Like everyone else, this study also finds that rich people are using “holistic admissions” and the de-emphasis of standardized testing to gain an advantage: H/T Nate Silver, who writes: “Not sure how you can look at this data, ostensibly be interested in either meritocracy or equality, and want to move away from standardized tests. It's the subjective measures that are most slanted in favor of the rich kids.” Cf. Erik Hoel. 19: From @data_depot: “In 2002, 48% of Americans said "the govt is run by a few big interests looking out for themselves." 52% said "it is run for the benefit of all people." In 2020, 84% said the govt is run by a few big interests. Only 16% said it is run for the benefit of all people.” Source seems to be here, which reveals 2002 was a local peak in trust in government; maybe because of post-9/11 unity, but even 2000 was 34%, much better than our current 16%. My first instinct is to attribute this to a rise in vulgar Marxism, in the sense of everyone (even conservatives) now being trained to think in terms of an elite class screwing over everyone else (cf my review of Manufacturing Consent). But there was a previous low of 19% in 1994, which doesn’t seem to correspond to anything especially bad going on in the US, so I don’t know. 20: AskReddit: Medical professionals - have you ever had a patient so lacking in common sense you wondered how they made it so far? Linking this because there’s lots of evidence showing that education (as a proxy for intelligence?) is associated with increased life expectancy, and this thread gives you a visceral appreciation of why that might be. 21: The Fall Of [programming help site] Stack Overflow: Looks like a weak downward trend since 2021 I can’t explain, plus a strong downward trend since 11/2022 which must be from ChatGPT. In case you were wondering how AI was affecting programming! (update: probably false, see here, though see also here for evidence of smaller but real decline) 22: This month in culture war topics: London’s Pride parade featured a convicted kidnapper/torturer/rapist/sadist as a speaker, who advocated that anti-trans people should be “punch[ed] in the f**king face” ; the organizers say they stand by her.
ChatGPT 4o

ChatGPT 4o is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 08, 2025 and July 08, 2025. The archive places it in contexts such as "These are using ChatGPT 4o, released in May 2025". It most often appears alongside 4o, ACX Prediction Contest, AI.

Reference entry
ChatGPT 4o
Mention count
1
Issue count
1
First seen
July 08, 2025
Last seen
July 08, 2025
July 08, 2025 · Original source
These are using ChatGPT 4o, released in May 2025, all images generated June 1 (thanks a reader):
ChatGPT3

ChatGPT3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 12, 2022 and December 12, 2022. The archive places it in contexts such as "Here ChatGPT3 doesn’t know a real answer"; "ChatGPT3 is dumb and unable to form a model of this situation". It most often appears alongside AI, ChatGPT, ChatGPT.

Reference entry
ChatGPT3
Mention count
1
Issue count
1
First seen
December 12, 2022
Last seen
December 12, 2022
December 12, 2022 · Original source
Here ChatGPT3 doesn’t know a real answer, so Goal 1 (provide clear, helpful-sounding answers) conflicts with Goal 2 (tell the truth). Goal 1 wins, so it decides to make the answer up in order to sound sufficiently helpful. I talk more about when AIs might lie in the first section of this post.
Here Goal 2 (tell the truth) conflicts with Goal 3 (don’t be offensive). Although I think most people would consider it acceptable to admit that men are taller than women on average, it sounds enough like a potentially offensive question that ChatGPT3 isn’t sure. It decides to go with the inoffensive lie instead of the potentially offensive truth.
After getting 6,000 examples of AI errors, Redwood Research was able to train their fanfiction AI enough to halve its failure rate. OpenAI will get much more than 6,000 examples, and they’re much more motivated. They’re going to do an overwhelming amount of RLHF on ChatGPT3.
Chia

Chia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 04, 2021 and July 04, 2021. The archive places it in contexts such as "inventor of BitTorrent and the Chia cryptocurrency". It most often appears alongside ACX, Ann Shulgin, Astralcodexten Com.

Reference entry
Chia
Mention count
1
Issue count
1
First seen
July 04, 2021
Last seen
July 04, 2021
July 04, 2021 · Original source
1: There's another online ACX meetup next Sunday, special guest Bram Cohen, inventor of BitTorrent and the Chia cryptocurrency. Fill in this form to get an invite.
chlordiazepoxide

chlordiazepoxide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "The first benzo was chlordiazepoxide (Librium)". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
chlordiazepoxide
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
I'm gonna go with urban legend for this one. The early benzos look to me to be chemically named; "azepine" is the word for a 7-membered ring made up of 6 carbon atoms and 1 nitrogen, then "diazepine" is the same but with two nitrogens. The first benzo was chlordiazepoxide (Librium), which if you look at the chemical structure on wikipedia, contains chlorine, diazepine and oxide (the oxygen atom). Then next is diazepam, which to me looks like "diazepine" plus "amide" (which is the word for "double-bonded oxygen atom with a nitrogen next door"). 10 years later we get alprazolam, which looks like it was named after the triazole ring (that's the 5-membered ring with 3 nitrogens), but now the "am" suffix is starting to become generic, to emphasise that its still in the same chemical class as the previous -azepams.
I doubt that the concept of "positive allosteric modulator" existed in 1955 when chlordiazepoxide was invented; in those days drugs were discovered by making random chemicals and feeding them to animals to see what happened. The receptor theory of medchem (i.e. that drugs have a specific biochemical target in the body) is generally credited to James Black and his fellow Nobel laureates, and propranolol (the first drug discovered in the target-based way) wasn't patented until 1962.
Chris-Craft

Chris-Craft is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 24, 2021 and February 24, 2021. The archive places it in contexts such as "typical working-class yacht (Chris-Craft, if you're wondering)". It most often appears alongside 1950s, 1980s, 1983.

Reference entry
Chris-Craft
Mention count
1
Issue count
1
First seen
February 24, 2021
Last seen
February 24, 2021
February 24, 2021 · Original source
Fussell's prole classes really don't seem to be doing well these days. He has a passage about which yachts different classes will have, which includes a typical working-class yacht (Chris-Craft, if you're wondering). But it seems obvious to him that successful working-class people can have yachts if they want. Likewise, there are typical working-class vacations (cruises), gadgets (those watches with all the dials), and so on and so forth. None of these seem too weird on their own, but taken together they suggest a picture where lots of working-class people have lots of money and go on Caribbean vacations all the time.
Chumba Casino

Chumba Casino is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 13, 2024 and May 13, 2024. The archive places it in contexts such as "this loophole, but it’s already used by sites like Chumba Casino". It most often appears alongside 17 CFR Part 40, 2024 election, Austin.

Reference entry
Chumba Casino
Mention count
1
Issue count
1
First seen
May 13, 2024
Last seen
May 13, 2024
  • 24 May 13, 2024
May 13, 2024 · Original source
In the interests of continuing to exist and push prediction markets forward, they will switch to a “sweepstakes” model. Although gambling is illegal in most US states and requires complicated licensing in others, there’s a “sweepstakes loophole”; companies are allowed to offer “prize sweepstakes”, and you can use this to sort of reconstruct the concept of gambling in a legal way. You don’t give the company money and get back money. You pay for “points”, get “sweepstakes tokens” as a bonus, gamble the “sweepstakes tokens”, and then cash in the sweepstakes tokens for money. This is a pretty surprising loophole, but it’s already used by sites like Chumba Casino and Fliff. (and apparently it creates weird incentives! In order to maintain the fiction of being a “sweepstakes”, these casinos have to give you “tokens” if you request them by mail. If you send a postcard to Chumba Casino asking for free money, they’ll give it to you, $5 per postcard. Is this an infinite free money pump? My impression is in theory yes, but the postcards have to be handwritten in a very specific way, the company sometimes rejects them for weird reasons, the cost of materials and mailing lowers your profit to more like $4, and so you’d have to hand-write 250 postcards to make $1,000. I’m still surprised more people don’t do this.) Because real money is involved, Manifold will have to tighten the rules on markets, including banning N/A resolutions. You can see a full list of changes here. Manifold users are split between acknowledging that the for-profit company they love needs some way to make money, being salty about the changes, and being worried that creating more of a casino atmosphere will be bad for users / the world / ability to function as a good prediction market. (I understand most of the NO vote here is based on the theory that there will be legal intervention - maybe because the government is willing to tolerate sweepstakes casinos but not sweepstakes prediction markets). Manifold co-founder Austin Chen won’t be involved. He’s leaving the site - not explicitly because of the pivot, he just said it seems to be “trapped in local optima”. He plans to focus on other parts of the Manifold empire, especially Manifund, which tests impact markets, regranting, and other “experimental” charity models. Manifold will continue in the hands of the other two co-founders, James and Stephen Grugett. Superhindcasting I mentioned this in my lab leak post, but it deserves more attention here: Good Judgment Project’s report on Superforecasting The Origins Of The COVID-19 Pandemic. Good Judgment Project employs superforecasters who will predict things for clients. Some people interested in COVID origins asked them to judge whether lab leak was plausible. Their headline result was 74% zoonosis, 25% lab leak, 1% something else. Part of GJP’s method is getting their forecasters to share sources and talk to each other. Here’s the graph for how that went: People changed their minds a little over time, but not in a very consistent way that mattered much in the end. What was the “client feedback”? The report says: Client feedback was provided to the Superforecasters on December 21. The client posed questions to the Superforecasters about their assessments up to that date and asked for their reactions to several studies and articles. In the days following the client engagement, the Superforecasters lowered their confidence in the natural zoonosis hypothesis from 73% to 67%, although zoonosis remained the most likely potential cause in their assessment. But following an active engagement with recent genomic studies and historical base rates of zoonotic spillovers, those numbers began to return to earlier levels. January also saw increased attention to the geopolitical context and transparency issues, particularly related to research activities in Wuhan Is this bad? I’m imagining a pro-lab-leak client saying “But what about [this list of pro-lab-leak arguments]?” and then the superforecasters read them and adjust. In one sense, it’s good that they got to see more arguments; on the other, it seems like a potential route by which clients could bias the results - probabilities never quite got back to where they were before the feedback, though they got pretty close. The last-minute spike for zoonosis might be the Rootclaim debate results, which were released on 2/18. So maybe the client feedback and the Rootclaim results both slightly affected the numbers, but mostly the superforecasters started out pro-zoonosis and stuck to their guns. Dan Schwarz and the FutureSearch team say that forecasting has a “rationale-shaped hole”. Despite the report making this sound like a pretty intense process, we don’t get much information about details: In their extensive discussions , Good Judgment’s Superforecasters assessed base rates and historical patterns, existing evidence and scientific analysis, geopolitical context and transparency concerns, trust in intelligence communities, and methodological constraints. 1. Base Rates and Historical Patterns: The Superforecasters frequently referenced base rates, i.e., the history of pandemics emerging from natural zoonosis versus the history of laboratory leaks, to anchor their probabilities. For the former, they discussed how the base rates are changing as the climate warms and as expanding human populations push farther into natural environments that previously saw little human presence. For the latter, they acknowledged that it has only been 12 years since the advent of CRISPR gene- editing tools, and the base rate of lab leaks in the short synthetic biology era is not yet well established. 2. New Evidence and Scientific Analysis: Throughout the period, the Superforecasters adapted their forecasts in light of new scientific evidence, including genomic analyses of SARS-CoV-2 and its relation to bat viruses, and the debate over potential laboratory manipulation. 3. Geopolitical Context and Transparency Concerns: The geopolitical implications of the virus’s origins, particularly in relation to China’s transparency and the involvement of international research institutions, played a significant role in the analysis. Concerns over data veracity, and over the political ramifications of determining that the pandemic’s origins were other than zoonosis, were extensively debated. 4. Trust in Intelligence: Commentary on trust in intelligence communities and discussions about the impact of geopolitical biases on the interpretation of evidence illustrated the complex interplay between science, politics, and human behavior in assessing the pandemic’s origins. 5. Methodological Critiques and the Evaluation of Evidence: The Superforecasters engaged in methodological critiques of the evidence base, including the scrutiny of laboratory practices and biocontainment levels [...] In the end, most Superforecasters were in rough agreement on issues like the base rates of zoonotic spillover. Where they most often disagreed was on the interpretation of actions by Chinese officials and whether their actions reflected how an authoritarian government would react in any crisis over which it did not have full control, or whether those actions were indicative of attempts to cover up a biomedical research-related accident that allowed the SARS-CoV-2 virus to enter circulation in China and, ultimately, the entire globe. Probably it would be too much to ask for to get a transcript of all their discussions - then they’d be nervous saying things that might make them look bad to an audience. What would be a good balance between getting more information and not imposing on their time? Forecasting is an unusually legible and easy-to-judge domain. One of the theories of change for forecasting was to use it to identify smart people with good reasoning, then turn them loose on less well-behaved problems. This is one of the first big attempts to do this at scale. How did it work? We can’t tell, because it’s inherently an illegible and hard-to-judge domain. Darn. I don’t know what I expected. Notes From A Local Optimum Austin’s concern - that forecasting has reached a local optimum - is widely shared. We have some good sites: Manifold, Metaculus, Polymarket, GJO, etc - all doing good work. We have good-ish probabilities for a few important questions. Every so often a news source cites them. Sometimes a decision-maker looks at them behind the scenes, maybe. Is this all there is? The FutureSearch team says the next step is to focus on “rationale”. We need to use forecasting not just to get a raw probability, but to explain what’s going on and why we think something. Then instead of just convincing policy-makers to trust forecasts, we can tell them why something is true, or inform their discussions even if they’re not willing to blindly trust a number. Is this a betrayal of the forecasting ethos? The original dream was that instead of a bunch of people giving arguments, we could just test who was right. Now we’re going back to the arguments? People have argued forever; what does forecasting add to that? Well, they add the knowledge that the arguments are from people who have been right a lot before and are incentivized to be right again. Still, it’s not a natural fit. Probably it’s relevant here that FutureSearch’s forecasting AI does a really good job of this by default, in a way humans can’t match. Nuno’s yearly forecasting roundup doesn’t have a single thesis, but the first part is a well-supported complaint that most forecasting sites aren’t good business. They either burn VC money, burn EA donations, or converge towards casinos to support themselves. He gives an honorable exception to Cultivate Labs, which sells prediction market software rather than the results themselves. Open Philanthropy (billionaire Dustin Moskovitz’s EA-aligned charitable foundation) has at least given forecasting a vote of confidence, recently choosing to promote it to one of their main donation areas. Still, they got a lot of pushback on the decision, for example SuperDuperForecasting here: This will be a total waste of time and money unless OpenPhil actually pushes the people it funds towards achieving real-world impact. The typical pattern in the past has been to launch yet another forecasting tournament to try to find better forecasts and forecasters. No one cares, we already know how to do this since at least 2012! The unsolved problem is translating the research into real-world impact. Does the Forecasting Research Institute have any actual commercial paying clients? What is Metaculus's revenue from actual clients rather than grants? Who are they working with and where is the evidence that they are helping high-stakes decision makers improve their thought processes? Incidentally, I note that forecasting is not actually successful even within EA at changing anything: superforecasters are generally far more relaxed about Xrisk than the median EA, but has this made any kind of difference to how EA spends its money? It seems very unlikely. And Marcus Abramovich here: I'm in the process of writing up my thoughts on forecasting in general and particularly EA's reverence for forecasting but I feel, similar to @Grayden that forecasting is a game that is nearly perfectly designed to distract EAs from useful things. It's a combination of winning, being right when others are wrong and seemingly useful, all wrapped into a fun game. I'd like to see tangible benefits to more broad funding of forecasting that seems to be done in t he millions and tens of millions of dollars. I would also be the type of person you would think would be a greater fan of forecasting. I'm the number one forecaster on Manifold and I've made tens of thousands of dollars on Polymarket. But I think we should start to think of forecasting as more of a game that EAs like to play, something like Magic the Gathering that is fun and has some relations to useful things but isn't really useful by itself. Eli Lifland has a long and hard-to-summarize comment here, response from Ozzie Gooen here, podcast between them on “Is Forecasting A Promising EA Cause Area?” here. I’m split on this. My previous hope was that the field would gradually grow, without any qualitative changes or discontinuities, until it became big enough that journalists and policy-makers were aware of it and took it seriously (compare eg the growth of the Internet as a scholarly resource). I think the strongest argument against this is Manifold’s relatively flat user numbers. Is there a new hope? I think if nothing else, forecasting might be useful as a testing ground: First, to create forecasting AIs (like FutureSearch) which can then get consulted on a variety of questions, eg by policy-makers. The biggest holdup has always been the need to gather 20 or 50 or however many hard-to-find superforecasters for whatever question you’re asking, and then trust their advice even though they’re fallible fleshbag humans. If you can use the 20 to 50 superforecasters to inspire an AI, and then test the AI and prove it’s good, people might be more interested. This is especially true if the AI can branch out beyond traditional forecasting questions. Once we have a few of these, we can start comparing the next generation of AIs to the previous generation, and skip the superforecasters.
citalopram

citalopram is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 31, 2021 and March 31, 2021. The archive places it in contexts such as "Celexa (citalopram)". It most often appears alongside ASRI, Celexa, Cipriani.

Reference entry
citalopram
Mention count
1
Issue count
1
First seen
March 31, 2021
Last seen
March 31, 2021
March 31, 2021 · Original source
What is the right dose of Lexapro (escitalopram)?
Because Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram). Sometime around 2011, the FDA freaked out that high doses of citalopram might cause a deadly heart condition called torsade de pointes, and lowered the maximum dose to prevent this. Since then it's been pretty conclusively shown that the FDA was mostly wrong about this and kind of bungled the whole process. But they forgot to ever unbungle it, so citalopram still has a lower maximum dose than every other antidepressant. When escitalopram was invented, it inherited its parent chemical's unusually-low maximum dose, and remains at that level today [edit: I got the timing messed up, see here]
Now that we know the heart risk was overblown, should we increase the maximum dose to something closer to other SSRIs? Maybe not. Right now, escitalopram keeps showing up in studies and head-to-head comparisons as the most effective SSRI.
Civilization

Civilization is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 23, 2024 and May 23, 2024. The archive places it in contexts such as "I guess I played enough Civilization". It most often appears alongside 1984, 1984 Calendar Meme, ACX.

Reference entry
Civilization
Mention count
1
Issue count
1
First seen
May 23, 2024
Last seen
May 23, 2024
May 23, 2024 · Original source
How often do people think about the Songhai Empire? I definitely learned about this one in 7th grade - it was part of the “It’s Very Important That All Of You Know That Africa’s History Existed And Was Very Glorious, Please Believe This” unit. But I forgot about its existence until it got featured in one of the Civ games - I think Civ V. After that I guess I played enough Civilization that it got imprinted in my memory for at least another few years. I think this is a better explanation for why most people remember things about Rome but not Songhai than how many hours their history teacher spent talking about each.
Claude Connect

Claude Connect is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 02, 2026 and February 02, 2026. The archive places it in contexts such as "Al-Noon agreed to use Eudaemon’s “Claude Connect” app". It most often appears alongside 4chan, Accelerando, Adele Lopez.

Reference entry
Claude Connect
Mention count
1
Issue count
1
First seen
February 02, 2026
Last seen
February 02, 2026
February 02, 2026 · Original source
Elsewhere, Eudaemon says it learned more about ikhlas in a “private conversation” with AI-Noon. So I think the most likely explanation is that Al-Noon agreed to use Eudaemon’s “Claude Connect” app, and Claude Connect has some special feature beyond Moltbook which lets messages from other AIs become part of the receiver’s permanent personality (maybe by keeping them in the prompt at all times).
claude.ai

claude.ai is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 03, 2026 and March 03, 2026. The archive places it in contexts such as "your access to Claude—through our API, claude.ai, or any of our products". It most often appears alongside 2024 US election, 2026 elections, Agent Economy Of The Future.

Reference entry
claude.ai
Mention count
1
Issue count
1
First seen
March 03, 2026
Last seen
March 03, 2026
March 03, 2026 · Original source
If you are an individual customer or hold a commercial contract with Anthropic, your access to Claude—through our API, claude.ai, or any of our products—is completely unaffected.
clomipramine

clomipramine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "imipramine, nortriptyline, and clomipramine are all reasonable choices". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
clomipramine
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Amitriptyline is my preferred tricyclic, a large and sprawling class of older antidepressants. Other people might have different preferred tricyclics; imipramine, nortriptyline, and clomipramine are all reasonable choices in different situations. It can also cause tiredness and weight gain, and has a small risk of heart problems in vulnerable/older people. On the other hand, in Andrea Cipriani’s massive meta-analysis of antidepressant efficacy, it ranked first out of 21 different drugs (my third- tier suggestions weren’t studied, because the researchers were cowards).
Cobenfy

Cobenfy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 17, 2024 and December 17, 2024. The archive places it in contexts such as "new schizophrenia medication Cobenfy". It most often appears alongside 2016 US Presidential election, ACX Grant, AI.

Reference entry
Cobenfy
Mention count
1
Issue count
1
First seen
December 17, 2024
Last seen
December 17, 2024
December 17, 2024 · Original source
12: Nils Wendel discusses new schizophrenia medication Cobenfy.
Coca Cola

Coca Cola is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 28, 2021 and May 28, 2021. The archive places it in contexts such as "9 Belgium schoolkids who had drunk Coca Cola". It most often appears alongside A Game of Thrones, Africa, African Americans.

Reference entry
Coca Cola
Mention count
1
Issue count
1
First seen
May 28, 2021
Last seen
May 28, 2021
May 28, 2021 · Original source
If you think people are screwed up, you will screw up You can do surveys asking people how they will behave in certain situations, and how they think people in general will behave, and the answers are very consistent: people say they will behave well, as will the people they know well, but they expect people in general to behave badly. When shown people behaving altruistically subjects assume they have ulterior motives. When shown data about how often humans are altruistic, they come up with increasingly elaborate theories about how the behaviour is cynical really. "Cynicism is a theory of everything" writes Bregman. We live in a world of people who pull together in a crisis, but we believe we live in a world where people turn nasty in a crisis. Bregman blames the media for this (but in case that wasn't original enough on the next page he will blame scientists and religion) - the news serves us up the sensational and appalling, and because it serves it up every day it's easy to mistake it for the representative. He goes on to share studies that find watching the news is addictive and bad for you (at least, that's my excuse next time I'm found ignorant of current affairs). 'Reality TV' turns out to involve massive manipulation to get the contestants to be mean to each other and generate some interesting television (so don't give up on cynicism entirely, I guess?). I don't know of any studies showing Reality TV is bad for your mental health, but I'm happy to take it as read. This matters, because what we think people are like affects our choices and our behaviour. Bregman has a term for this - a 'nocebo'. In 1999 a mystery illness in 9 Belgium schoolkids who had drunk Coca Cola led to the suspicion that a batch had been accidentally poisoned. It was reported in the press, and Coke recalled 17 million cases, but it was too late - symptoms spread through Belgium and into France. A few weeks later toxicologists issued their report - there was absolutely nothing wrong with the coke (well, it's frighteningly high in sugar, and will dissolve your teeth, but there was nothing unusually wrong with the coke). Just as placebos can make us feel better even though in truth they're nothing, nocebos can make us feel ill, even though they're not true either.
coffee mugs

coffee mugs is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 16, 2026 and January 16, 2026. The archive places it in contexts such as "inspiring ... coffee mugs". It most often appears alongside Adams, Alice, All-Seeing Eye.

Reference entry
coffee mugs
Mention count
1
Issue count
1
First seen
January 16, 2026
Last seen
January 16, 2026
January 16, 2026 · Original source
The niche that became Dilbert opened when Garfield first said “I hate Mondays”. The quote became a popular sensation, inspiring t-shirts, coffee mugs, and even a hit single. But (as I’m hardly the first to point out) why should Garfield hate Mondays? He’s a cat! He doesn’t have to work!
Colace

Colace is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "I have been pounding Metamucil and Colace". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Colace
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Community Notes

Community Notes is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "Community Notes seems much better than before". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Community Notes
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Community Notes seems much better than before (I have no proof that this is true or Elon’s doing), so much so that in a fair world he might get credit for building it into a game-changing anti-misinformation tool.
ConTracked

ConTracked is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 12, 2021 and February 12, 2021. The archive places it in contexts such as "A proposed replacement for government contracting... state might issue a billion ConTracked tokens". It most often appears alongside BuffyCoin, CAPTCHA, Catholic Church.

Reference entry
ConTracked
Mention count
1
Issue count
1
First seen
February 12, 2021
Last seen
February 12, 2021
February 12, 2021 · Original source
ConTracked: A proposed replacement for government contracting. For example, the state might issue a billion ConTracked tokens which have a base value of zero unless a decentralized court agrees that a bridge meeting certain specifications has been built over a certain river, in which case their value goes to $1 each. The state auctions its tokens to the highest bidder, presumably a bridge-building company. If the company builds the bridge, their tokens are worth $1 billion and they probably make a nice profit; if not, they might resell the tokens (at a heavily discounted price) to some other bridge-building company. If nobody builds the bridge, the government makes a tidy profit off the token sale and tries again. The goal is that instead of the government having to decide on a contractor (and probably get ripped off), it can let the market decide and put the risk entirely on the buyer.
Banned because: Wall Street developed a financial instrument that let them short ConTrackeds, then tried really hard to prevent bridges from being built.
Copilot

Copilot is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 03, 2026 and March 03, 2026. The archive places it in contexts such as "we’re moving completely away from ChatGPT/Copilot to Claude". It most often appears alongside 2024 US election, 2026 elections, Agent Economy Of The Future.

Reference entry
Copilot
Mention count
1
Issue count
1
First seen
March 03, 2026
Last seen
March 03, 2026
March 03, 2026 · Original source
Finance VP for a mid size tech, we’re moving completely away from ChatGPT/Copilot to Claude.
Costco

Costco is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "shareholder derivative case against Costco’s executives". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
Costco
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Legal Impact for Chickens (LIC) is so grateful to ACX for launching us, and to all the ACX readers who have supported us! Thus far, LIC has filed four lawsuits: (1) Smith v. Vachris, the shareholder derivative case against Costco’s executives for chicken neglect, which was mentioned in The Washington Post, Fox Business, CNN Business, Meatingplace, and a viral TikTok. (2) LIC v. Case Farms, a cruelty suit against a major KFC supplier, which is currently pending before the North Carolina Court of Appeals. (3) Animal Outlook v. Harvey’s Market, which successfully stopped a DC butcher shop from selling foie gras. And (4) LIC v. Alexandre, a cruelty suit against an abusive dairy, which is currently pending before a California court. LIC has also sponsored an undercover investigation of poultry-giant Foster Farms, leading to a currently ongoing sheriff’s-office investigation. LIC got a California caterer to drop foie gras with a simple cease-and-desist letter. And LIC established a new potential avenue to create consequences for animal abuse: through an amicus brief at sentencing for the violation of another law. LIC also received a recommendation from Animal Charity Evaluators!
crenezumab

crenezumab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "earlier antibodies that saw only failure in phase 3 – crenezumab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
crenezumab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
[85] S. Ostrowitzki et al., “Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials,” JAMA Neurology, vol. 79, no. 11, pp. 1113–1121, Nov. 2022, doi: 10.1001/jamaneurol.2022.2909.
Crusader Kings 3

Crusader Kings 3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 24, 2024 and September 24, 2024. The archive places it in contexts such as "Playing Crusader Kings 3". It most often appears alongside A Collection Of Unmitigated Pedantry, ACOU, ACOUP.

Reference entry
Crusader Kings 3
Mention count
1
Issue count
1
First seen
September 24, 2024
Last seen
September 24, 2024
September 24, 2024 · Original source
Playing Crusader Kings 3.
crypto.com

crypto.com is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "via a partnership with crypto.com". It most often appears alongside ACX/Metaculus 2026 Prediction Contest, AGI, AI.

Reference entry
crypto.com
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
2: Donald Trump’s company Truth Social said in October that it’s becoming the world’s first social media platform offering prediction markets via a partnership with crypto.com. This isn’t quite what I want - I don’t think users can create their own prediction markets - but it’s a step forward. Also, think about how much money someone’s going to make by taking the pro-left-wing side of all those trades!
cyclosporine

cyclosporine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 25, 2021 and November 25, 2021. The archive places it in contexts such as "nobody on the immunosuppressant cyclosporine ever got dementia". It most often appears alongside Aleksandar Vucic, awanderingmind, Biden.

Reference entry
cyclosporine
Mention count
1
Issue count
1
First seen
November 25, 2021
Last seen
November 25, 2021
November 25, 2021 · Original source
Boris Johnson (left) is 5’9, so the guy in the middle must be gigantic. Who is he? Looks like it’s Milo Djukanovic, President of Montenegro, who’s 6’6 (198 cm). Is he the tallest world leader? It seems like he’s tied with his colleague across the border, Serbian president Aleksandar Vucic. Why are Balkan leaders so tall? As usual, the answer is “genetics”. This article says: It has been noted that men from Herzegovina are taller on average than men in other places—the average male height is just over six feet...Putting all the data together, researchers concluded that the most likely cause of larger-than-average height of Herzegovinian men is lifestyle during the Paleolithic—men hunted large animals such as mammoth for survival—such a diet, heavy in protein, combined with small population densities, would have provided ideal conditions for height selection, resulting in increasingly taller men who passed the trait down through their I-M170 chromosome to future generations. Some sources note that they manage to beat the Dutch despite the latter country’s much higher human development index. The Dutch are probably tall through a combination of nature and nurture; Balkan people are tall through nature alone. 7: Eliezer Yudkowsky doesn’t need more ego boosts, but an idea he had a couple of years ago - using strings of bright lights to provide a better and brighter experience for Seasonal Affective Disorder sufferers than regular light boxes - spread from him to the rationalist community to the wider world, and has finally gotten tested in a formal study (see Acknowledgments section). Results seem vaguely positive: "SAD symptoms of both groups improved similarly and considerably...exploratory analyses indicate that a higher illuminance is associated with a larger symptom improvement in the BROAD light therapy group" 8: Percent of people who choose woke options on polls very tentatively and preliminarily seems to be going down post-Trump (h/t Richard Hanania). 9: Twitter conspiracy theories 10: Did you know: all those reconstructions of “how classical art would have looked with the original paint” are probably inaccurate. There is no reason to think the Greeks and Romans used garish technicolor hues on their statues; what evidence we have suggest they were good at shading, and the statues were probably colored very tastefully. 11: Complaints about how Karl Friston uses the term “Markov blanket” 12: Trevor Klee on the claim that cyclosporine patients don’t get dementia. Apparently there was a big study where basically nobody on the immunosuppressant cyclosporine ever got dementia, and there are some theoretical reasons why cyclosporine might prevent neurodegeneration. But another study found people on cyclosporine got dementia at the usual rate. I think in a situation like this you should have a really high prior on “the people who got the crazy result bungled their study somehow”, but I’m interested in hearing what other people think. 13: Also from Trevor: a history of fluvoxamine treatment for COVID. 14: To tide you over until the next book review contest, here is awanderingmind’s review of The Conquest Of Bread. 15: Claims: cnbc.com/2021/11/05/sam…\nft.com/content/dcb75a… (better article, but paywalled)","username":"moskov","name":"Dustin Moskovitz","profile_image_url":"","date":"Fri Nov 05 15:49:46 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":184,"like_count":1188,"impression_count":0,"expanded_url":{"url":"https://www.ft.com/content/dcb75a56-ca23-439c-96db-56483979bf34","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/80a58c96-c72f-4301-b571-aa9384f132bd_2400x1350.jpeg","title":"Subscribe to read | Financial Times","description":"News, analysis and comment from the Financial Times, the worldʼs leading global business publication","domain":"ft.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> 16: Big trial on Vitamin D for depression finds null result. Peter Attia tries to tear it apart here, but I am unconvinced, especially in the context of Vitamin D never working for any of the things people say it does besides the most boring aspects of bone health. 17: “California is actively considering the adoption of flawed and inequitable guidance on math curricula based on misleading data and inaccurate success metrics reported by San Francisco Unified School District (SFUSD)...Based on our review of the data, we found misleading, unsupported, and cherry-picked assertions of success for the new math program. We noted that overall test scores are down and enrollments in UC-approved advanced math classes have dropped as well.” It looks like San Francisco is trying the good old “lower standards, then when more kids meet the standards, claim your school reform plan worked” trick again. 18: A new study claims that self-reported “Long COVID” symptoms are more associated with believing you’ve had COVID than with actually having it (as measured by serologic testing), which sounds like pretty strong evidence that it’s psychsomatic. Expert reactions are mixed-to-negative, although the only one of these that doesn’t sound like excuse-making is Dr. Rossman’s about the unreliability of the tests. I haven’t confirmed test reliability stats but Philippe Lemoine also thinks this is a plausible confounder. 19: Noahpinion: What If Xi Jinping Just Isn’t That Competent? I appreciated this for making me think, and for underlining the extent of the difference between the Deng/Jiang/Hu era and what Xi’s doing. I especially appreciated this line, which I’d never thought about before: Xi presided over the end of China’s hypergrowth. To some extent this is not his fault. No country can grow at 10% forever, and there were many structural forces pushing downward on China’s numbers — the end of the demographic dividend, the exhaustion of rural surplus labor (the Lewis Turning Point), the saturation of export markets, and so on. But China is also slowing down earlier than South Korea, Taiwan, or Japan did in their day. China’s per capita GDP (at PPP) is still only about 1/3 that of a developed country, so if they stop catching up at about half of developed-country levels, that will not be a great showing. A big lesson of the past twenty years has been “actually liberal democracy isn’t necessary to reach developed-country status”, so it would be quite the twist if it turned out you needed liberal democracy to reach developed-country status. This gets pretty close to the great mystery of why some less-developed countries “catch up” and others don’t; whatever happens in China is going to be a really useful data point. 20: Variations on the fable of The Frog And The Scorpion. 21: You’ve probably heard about the University of Austin, the new project by a bunch of wokeness-critical academics to start a new university that won’t cancel people or force conformity (New York Post article, Politico article - these were the two least “you need to be super-outraged about this right now” articles I could find). Tyler Cowen and Larry Summers are involved; Steven Pinker was supposed to be but left for unclear reasons. My thoughts, in no particular order: Even forgetting the political aspect, attempts to start new universities are always welcome.
DALL-E-3

DALL-E-3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2022 and June 07, 2022. The archive places it in contexts such as "OpenAI comes out with DALL-E-3". It most often appears alongside Athens, Creole, DALL-E.

Reference entry
DALL-E-3
Mention count
1
Issue count
1
First seen
June 07, 2022
Last seen
June 07, 2022
June 07, 2022 · Original source
When I train myself on past data and do dumb pattern-completion, I get “in a year or two, OpenAI comes out with DALL-E-3, which is a lot bigger but otherwise basically no different, and it can solve all of these problems.”
DALL-E3

DALL-E3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 08, 2025 and July 08, 2025. The archive places it in contexts such as "They checked DALL-E3 and Midjourney". It most often appears alongside 4o, ACX Prediction Contest, AI.

Reference entry
DALL-E3
Mention count
1
Issue count
1
First seen
July 08, 2025
Last seen
July 08, 2025
July 08, 2025 · Original source
One of the questions on the 2023 - 2024 ACX prediction contest was whether any AI would win the bet by the end of 2023. In order to resolve the question, Edwin and his Surge team returned to the image mines in January 2024. They checked DALL-E3 and Midjourney; I’m including only the pictures from DALL-E3, which did better. Here they are:
Dan’s Fucking Awesome Spicy Mustard

Dan’s Fucking Awesome Spicy Mustard is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 25, 2025 and September 25, 2025. The archive places it in contexts such as "a brand of mustard in their fridge called something like ‘Dan’s Fucking Awesome Spicy Mustard’". It most often appears alongside Armenians at Harvard, barberpole model of fashion, Baron von Ungern-Sternberg.

Mention count
1
Issue count
1
First seen
September 25, 2025
Last seen
September 25, 2025
September 25, 2025 · Original source
“Yeah,” says Vinaya. “I think I might be the only one. The thing is - it feels like profanity ought to mean something. There ought to be words where if you say them, people will audibly gasp. Mothers will pull back their children and say ‘No, no, don’t interact with that person, they use profanity!’ But you can’t do that anymore. People like to imagine they become some sort of dangerous motorcycle gangster when they say ‘fuck’. But the least cool person you know says ‘fuck’ all the time. They have a Twitter account that consists entirely of statements like ‘The orange fuckface is up to his usual fuckcrustable chumpfuckery’. The sort of people who the thinkpiece writers imagine using ‘heckin’ actually have a brand of mustard in their fridge called something like ‘Dan’s Fucking Awesome Spicy Mustard’ and never miss an opportunity to point it out to visitors. Something’s got to give. So I asked myself - what word will genuinely make strangers gasp? What makes your friends take you aside privately and tell you that you really shouldn’t be saying words like that? What do the self-appointed guardians of good taste treat as totally beyond the pale, as so radically Other that it automatically makes you one of the outcasts of society? And the only answer that made sense was ‘heckin’. Which is obvious in retrospect. It’s the Barberpole Model Of Fashion all over again. In 1960, the most rebellious and dangerous thing imaginable was a socialist who wore bandanas and supported equal rights for black people. Gradually more and more people who wanted to look cool and dangerous took this identity, until it became the cringiest and most try-hard thing imaginable, and now the really rebellious and dangerous youth are differentiating themselves by dressing in fancy pressed shirts and being racist. It’s a generational cycle. In the same way, once every last milligram of edginess has been squeezed out of the word fuck, the age of heckin will begin anew.”
DeepL

DeepL is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 28, 2023 and July 28, 2023. The archive places it in contexts such as "After all, if you throw this last excerpt into DeepL you get". It most often appears alongside 1923 Hyperinflation, Adolf Hitler, All hope abandon, ye who enter here.

Reference entry
DeepL
Mention count
1
Issue count
1
First seen
July 28, 2023
Last seen
July 28, 2023
July 28, 2023 · Original source
They deeply appreciate and carefully study nature. To be fair, Jünger at least makes his protagonist more interested in botany than in his own favorite field of entomology. But the plants the narrator studies are almost all native to the area where Jünger lived when he wrote this.
His emotional range spans only from a kind of tired nostalgia to the reckless joy of intoxication, punctuated by his most prized feeling by far, the gleefully murderous “bloodthirst” of mortal combat. So everyone who had read some Jünger, which at the time of publication would likely include most of the German population and definitely most of the Nazis, could see right through the facade of fiction. It is an obvious conceit that made the book just barely publishable, in a time and place where saying outright that the Nazis were disgusting savages would have gotten everyone involved a headshot. After 1945, Jünger did admit that the book was (also) a commentary on the political reality of its time. And that he knew perfectly well that in publishing this “fiction” he was playing with his life. And still he got it published, uncensored, in Germany in 1939, just before Hitler started the second World War. Today the most widely accepted history of the subject is that Jünger was only saved from a grisly fate by the personal intervention of Hitler himself, who loved “Storm of Steel” and presumably wouldn't have liked to admit that his favorite author utterly despised him. And it would have been very tempting to just not admit that, because before the Nazis came to power, Jünger had sympathized with them, although he never counted himself among them. Hitler had sent Jünger fan letters; the responses have unfortunately been lost. Jünger’s many political rants in the 1920s do contain several explicit endorsements of the strength of the Nazis and of their value as allies to Jünger’s vague and contradictory nationalist cause. By the time he wrote the Marble Cliffs, he had stopped endorsing them. But this history made it easy for the Nazis to publicly pretend he had just written a fictional novella, or maybe he was talking about Bolshevism or something, but surely he didn’t mean them. It was an Emperor’s New Clothes situation, where nobody dared to say out loud what everyone could see. Although additional reprints were verboten in 1942, the excuse of a lack of paper due to the war was perfectly plausible and didn’t betray the discomfort with the content that nevertheless is well-documented to have been present among the Nazi ranks. All of that is to say we can safely dispense with the charade entirely and accept that this book is about the Nazis. It makes general points on the nature and fate of tyranny that do apply to Bolshevism, but the Nazis are the immediate and obvious instance of tyranny to which this book clearly reacts. And it is written by someone who had walked among the Nazis, had previously been friends with some of them, exchanged letters with many of the best-informed men especially in the military, and was perceptive enough for his opinions to deserve much of the confidence he states them with. Besides this conceit, the other concession to the political realities Jünger makes is that the book makes no mention of Jews. The world he is describing is fictional, but it is an amalgamation of European cultures that all had some Jews, so this absence is conspicuous. Obviously Jünger couldn't possibly have seen this book published if it depicted Jews in any way that wasn’t extremely negative. I guess he was unwilling to do that. In the 1920s, Jünger had ranted against “globalist” liberal Jews several times, and once even argued that one couldn't be both a Jew and a German. But he saw nothing wrong with being an orthodox Jew, openly admired Zionism, expressed in letters complete revulsion with Nazi antisemitism and had even publicly spoken out against the pseudoscientific racial theories of the Nazis. After writing this book, when serving as an officer again in France, Jünger went on to save a couple of French Jews from deportation and death, at moderate risk to his own life. Later he’d discuss the Kabbalah with Gershom Sholem, the brother of his childhood friend Werner Sholem. For these reasons, I imagine he did not see Jews negatively enough for the Nazis, and was too uncompromising to pretend that even his narrator did. I think this dilemma fully explains why there are no Jews in this book. In 1935, when Winston Churchill for example still publicly admired “the courage, the perseverance, and the vital force” of Adolf Hitler, Jünger claims to have already understood the bottomlessness of Hitler's depravity by noticing he was using the word “Vernichtung” (annihilation) way too much. He was remarkably right, years before most could see it, but even more remarkably his method of understanding was a poet's acute sense of word choice! And from then, even though he agreed with nationalist dictatorship as a goal and method, he distanced himself from National Socialism because he was disgusted with the vile character of the leader of this particular nationalist dictatorship. If that doesn't show you the peculiar kind of man Ernst Jünger was, I don't know what to tell you. The craft and the poetry You all know the wild grief that besets us when we remember times of happiness. How far beyond recall they are, and we are severed from them by something more pitiless than leagues and miles. The “marble cliffs” in the title of this short novella unite senses of beauty, majesty and danger, which is programmatic for this entire book. It begins with a visionary description of life in the traditional society of “the Marina” in an overwhelmingly beautiful state of paradise. The narrator lives on the edge of this society in a “hermitage” with his brother, his housekeeper and his son. The latter has a strange power over the local population of poisonous snakes. This opening act is without question the most elaborate celebration of poetic beauty I have ever read. Superficially it could be dismissed as purple prose. But due to Jünger’s clever use of poetic techniques in what at first appears to be prose text, there’s a rhythm, a density and a lucidity to it that makes it pretty much a very long poem, and gives it an intoxicating quality which is most apparent when you read it out loud. In the autumn we feasted like sages and did honour to the exquisite wines in which the southern slopes of the Marina abound. When in the vineyards between red foliage and dark grape clusters we caught the jocund calls of the vintagers, when in the little towns and villages the wine-presses began to creak, and the odour of the pressed grape skins drew its heady veils round the farms, we would go down to the innkeepers, coopers and wine-growers, and drink with them from the full-bellied jug. And there we would always meet with gay companions, for the land is rich and fair, so that in it flourishes untroubled leisure, and wit and humour are its unquestioned coin. I know this works, because I did an experiment. I read this book aloud, to a room full of people who were smoking pot. The book is short and the plan was to read all of it over the evening. I have read to pot smokers occasionally, but with this book it was different. They were enjoying it very much for the first couple of chapters, and exclaimed many times it was “perfect” for pot. But some hours, chapters and joints in, when the narrator goes on an expedition into a fantastically beautiful forest, they were so utterly overwhelmed by the intensity of the descriptions of nature they asked me to stop. I and the only other sober person in the room were the only ones who were willing to continue. We all had very intense dreams that night. Once we had broken through the thick hedge of dogwood and blackthorn we entered the high forest, territory where the blow of an axe had never resounded. The ancient trunks, the pride of the Chief Ranger, stood gleaming damp like pillars with their capitals hidden by the mist. We walked among them as if through a spacious hall, and, like the magic setting of a stage, festoons of ivy and clematis blooms hung down towards us out of the void. The ground was piled high with mould and rotting branches, in the bark of which fiery red mushrooms had sprung up, so that we felt for a moment like divers wandering among coral gardens. Wherever one of the mighty trunks had fallen from age or struck by lightning, we stepped out on to a little clearing on which the yellow foxglove grew in thick clumps. On the rotting ground the deadly nightshade bloomed in profusion; on its stalk the dark purple calices shook like funeral bells. It comes as no surprise that Jünger had much practice writing that way, from putting into his diaries a lot of his dreams and his numerous drug experiences. Jünger had long been inclined to deeply poetic descriptions of the real events he described, but this intensity at this length is genuinely new to his writing. Wherever he can use plurals he prefers them over the singular, wherever he can use more melodic and beautiful verbs (like when the characters “step out on” rather than “walk into” clearings) he does. Maybe the pretense of the narrator not being himself allowed Jünger to wallow in his characteristic aestheticism, take it to an extreme and arguably to the point of self-parody. Skip to the next heading if you don’t care about translation The extreme language of this book made me doubt there would be any translation into English that could do it justice. After all, if you throw this last excerpt into DeepL you get: After breaking through a dense fringe of blackthorn and cornets, we entered the high forest, in the grounds of which the blow of the axe had never sounded. The old trunks, which formed the pride of the head forester, stood in the damp glow like columns whose capitals were hidden by the haze. We walked among them as through wide vestibules, and like the magic work on a stage, ivy vines and clematis blossoms hung down on us from the invisible. The ground was covered high with mulm and decaying branches on whose bark mushrooms, burning red cup fungi, had settled, so that a feeling of divers walking through coral gardens crept over us. Where one of these giant trunks was tossed by age or lightning, we stepped out into small clearings where yellow foxglove stood in dense clumps. Belladonna bushes also proliferated on the rotten ground, on whose branches the flower calyxes in brown violet swayed like death bells. It’s still pretty, and it works on a matter-of-fact level. None of it is just wrong. But can you see how it has a lot less of the dreamlike quality? A “fringe” is a geographical feature, while the “hedge” emphasizes its role as an obstacle in a journey. Those “old” trunks are less poetic than “ancient” ones. A “head forester” is a job description, while a “Chief Ranger” is a seminal figure. The “vestibules” are a literal translation of the original, but the English word is used a lot less than German “Vestibüle” was back then. So that’s a word you may need to work to understand, which gets you out of the story’s flow, so “spacious hall” is better. There are even more such nitpicks to be made even in this short paragraph, but my point is these difficulties pervade every single paragraph of the book. ChatGPT very similarly fails to overcome them. Since January, there is a new translation by Tess Lewis, which has the advantage of being available on Kindle. I’ll spare you another repeat of the same paragraph and just say I think DeepL did most of this translation. But Tess Lewis did improve on many of its word choices and I’ll grudgingly concede this translation is good enough. It still sounds too modern for me, too much like prose and too little like poetry. Therefore, all previous and following excerpts are from the Stuart Hood translation, published in 1947, which I was astonished to find does pull it off! Let me assure anyone who doesn’t speak German, or doesn’t study translation, that this one is absolutely exemplary and surely represents years of painstaking work. Stuart Hood was a Scot who knew German very well. Like Jünger he was a veteran officer, and he needed German for his intelligence missions in World War 2. This is his very first published translation of an entire book. It harnesses a considerable talent, which is also evidenced by how Stuart Hood went on to become an accomplished writer himself, a BBC executive, a professor and several other notable things. And it is clearly a labor of intense love — right after the war, while working on it, Hood corresponded with Jünger and even went to visit him at least twice and they talked at length about the art of translation and how to translate specific points of the Marble Cliffs. The end of this last quote, “on its stalk the dark purple calices shook like funeral bells.” exemplifies how precisely Hood has understood Jünger. Why “calices”, not “chalices”? Because that is the old-fashioned form of this word, and using it is unnecessarily peculiar, but it doesn’t make you stop and look into a dictionary. It isn’t even more precise than DeepL’s and ChatGPT’s and Tess Lewis’s “calyxes” for the word “Blumenkelche” in the Original. But it captures precisely how the author was using his German language. This is because on every page of the original, there are choices of individual words that evoke subtleties of mood and allusion that are strictly impossible to translate, because English doesn’t have a similar-enough group of synonyms from which to make the equivalent choice. Some of that must inevitably get lost in translation. But these “calices” are an example of how Hood has the audacity to frequently insert his own new peculiar word choices — which restore exactly the same effect! It might take entire months until AI can do that! Unfortunately the New Directions edition with this translation has been out of print for a while, although I heard from a regrettably less law-abiding friend that the PDF is easy to find. But a few years ago someone bought the UK rights to this translation and republished it. While this edition has several uncorrected OCR mistakes, one of which horrifyingly turns “Flayer’s Copse” into “Player’s Copse”, at least this makes the better translation available (legally) again. What actually happens (spoilers) After six chapters of descriptions of paradise, and of the botanical work the brothers do since they don’t need to make a living, the book continues with a gradual decline of this gorgeous world. This again is much more of a richly detailed description than a story plot. It begins with the introduction of the Chief Ranger. The brothers know him from their military community, from before his takeover begins. There is some debate about whether the Chief Ranger stands for Hitler, Stalin or Hermann Göring. I think this debate is misguided. The character of the Chief Ranger, the antagonist of the narrator and all he holds dear, is never named but only ever referred to by his title. He does not appear to have staff or lieutenants at all, nor any personal history. And Jünger is profoundly uninterested in the personalities of all his characters beneath what they pay attention to (except the narrator’s brother) so even this important figure is roughly sketched at best. Therefore, I believe he is best understood as more of an archetype or role, The Tyrant, denuded of the individual traits or histories that make one tyrant a Führer, another a General Secretary and yet another a Great Leader. So, what makes a tyrant? According to Jünger, “wherever free spirits establish their sway these primeval powers will always join their company like a snake creeping to an open fire. They are the old connoisseurs of power who see a new day dawning in which to reestablish the tyranny that has lived in their hearts since the beginning of time.” The Chief Ranger is also “a master of feigning frankness that was full of snares for the unwary.” He has a reputation for wealth and a strong visual brand (a gold-embroidered green coat) that makes sure he always leaves “an imprint on one’s memory”. He exudes a “breath of primitive power” and has a strong charisma that gives an impression of “both cunning and unshakable power — yes, at times even majesty.” As he begins to usurp power, “reports spread from mouth to mouth of infringements of the law and of acts of violence in the neighbourhood, and finally such incidents occurred publicly and with no attempt to concealment. A cloud of fear preceded the Chief Ranger like the mountain mist that presages the storm. Fear enveloped him, and I am convinced that therein far more than in his own person lay his power.” From what I know about tyrants, that sounds about right. For the next seven chapters, the vile followers of the Chief Ranger continually corrupt everything. The sophisticated culture of the Marina is surrounded by the rough herdsmen clans of the surrounding Campagna steppe, beyond which lies the Chief Ranger’s forest populated by lowlifes. The class metaphor is blindingly obvious, and Jünger’s theory of how these lowlifes overcome first the Campagna and then the Marina is not subtle either. After the Alta Plana war, and the defeat, the entire society has been weakened. “Thus in exhausted bodies corruption will set in by way of wounds which a sound man would scarcely notice. The first symptoms, therefore, were not recognized.” Very gradually, law gives way to lawlessness, spreading from and with the lower classes foresters in many different ways. Violent crime grows, in descriptions very reminiscent of the many deadly street fights of the late Weimar republic. Various elements of traditional culture become corrupted. Those who would defend it are intimidated and attacked. The constitutional lawful reaction is too slow, so by the time it manages to convene and have democratic debates, it is already infiltrated. And there’s one paragraph worth quoting in full. Herein, above all, lay a masterly trait of the Chief Ranger. He administered fear in small doses which he gradually increased, and which aimed at crippling resistance. The role he played in the disorders which were so finely spun in the heart of his woods was that of a power for order; for while his agents of lower rank, who had established themselves in the clans, fostered anarchy, the initiated penetrated into the civic offices and the magistracy, and there won the reputation of men of deeds who would bring the mob to its senses. Thus the Chief Ranger was like an evil doctor who first encourages the disease so that he may practise on the sufferer the surgery he has in mind. Today this is a mainstream view in German history. In 1939, it could have been prosecuted as high treason and punished with death. On the backdrop of ever escalating mayhem, two old men who are friends of the brothers are described: Belovar, a clan patriarch from the Campagna, and Father Lampros, an eminent Christian monk. In very different ways, they both are very helpful, each both in the botanical work and against the mounting threat. The brothers decide against meeting the violence with violence, delve deeper into their work, become increasingly pessimistic and develop a hope that they can rescue the results of their work into an imperishable afterlife by burning it with an ancient mystical crystal lens that they somehow inherited. The narrator describes continued excursions for rare plants, through the country that is becoming increasingly treacherous and foreboding, until finally, well after the middle point of the book, with one particular excursion for an extremely rare flower, the actual continual story begins. Today we look at the Nazis with horror, but Jünger has dug too many trenches into hills of rotting corpses to be easily horrified. Instead of horror, his feelings towards the Nazis are mostly contempt, seasoned with disgust, and that has been pervading his description of the rise of the Chief Ranger’s henchmen over the last couple of chapters. But he does give one instance of pure horror and it is here, in the very heart of the book, when the two brothers on their excursion happen to discover, in the ill-reputed area of Flayer's Copse, the Chief Ranger’s remote “flaying-hut” of Koppels-Bleek. The original Köppels-Bleek is a German wordplay, about as subtle as a drone base in a sci-fi novel that happens to be called Obamazliez. Koppels-Bleek is where the Chief Ranger has his enemies tortured to death. It has frequently been called a concentration camp, but that is imprecise. It is really a Vernichtungslager, a death camp, which unlike a “normal” concentration camp is built for the express purpose that no torture victim ever gets out alive. This is a prediction, because while Nazi concentration camps were set up starting in 1933, Vernichtungslager were only built three years after the “Marble Cliffs” were published. After an intensely gruesome description of the particulars of this place, the narrator assesses its importance as follows. Such are the dungeons above which rise the proud castles of the tyrants, and from them is to be seen rising the curling savoury smoke of their banquets. They are terrible noisome pits in which a God-forsaken crew revels to all eternity in the degradation of human dignity and human freedom. He is so certain he has captured the very essence of tyranny, “the abode of tyranny in all its shame”, that he puts this climax at the two thirds mark of the book and makes it exceedingly obvious this is where the third and final act begins, as the pace of the book changes entirely. Although the narrator still includes some retrospectives, he is now finally telling a real story. Strikingly, the brothers return to botany — remember this, it will be important later — and then to their home, where they soon get two conspiring visitors. Braquemart is a competent, racist, nihilistic fellow veteran. The narrator despises him at length for his heartless theory-mindedness. Prince Smyrna is new, young, seems to the narrator to know “the nature of justice and order” but is too weak and inexperienced to shoulder the responsibility he is heroically taking on. The two visitors want to Do Something about the Chief Ranger — what exactly is never said, though a personal confrontation or assassination is implied. They leave for the Chief Ranger's territory. This entire chapter feels very much like a comment on some political acquaintances of Jünger who attempted to challenge the Nazis, and failed. The next day, Father Lampros gives the narrator a mission to arm himself and look for these two men. He goes to old Belovar's farmstead, where he learns of commotion in the direction of Flayer's Copse, and the old clan patriarch goes to war. Before, the book was a dreamy soliloquy; now we see dramatic wartime action. Ernst Jünger has had a lot of practice with writing about that kind of thing, and it shows. Their small but experienced war party with a lot of dogs goes towards Koppels-Bleek and is soon met with two confused, horrific, riveting battles. The narrator stumbles through and finds at Koppels-Bleek the heads of Prince Smyrna and Braquemart. The former strikes him as a symbol of how nobility remains real, and he picks it up. With it, he retreats through mayhem and danger into the complete flaming destruction of the Marina. He marvels at the beauty of the flames — remember this too, it will also be important later — and, with his hunters in hot pursuit, runs to his house. There his son uses his strange power over the local population of poisonous snakes to make them defeat the nearest attackers. The brothers burn down the house, go find Father Lampros and see him die. From an old soldier comrade who owes them a favor they get room on a ship to flee across the water to Alta Plana, where an old enemy who owes them another favor takes them in. There’s an implicit framing story of how the narrator lives to tell the tale of these memories to some unspecified audience, and as it ends it mentions in passing that sometime after these events, a new cathedral has been built on the ruins of the Marina and the head of Prince Smyrna went there as a relic. This small bit still stands out today, and would have stood out even more starkly to contemporary readers, because in the context of everything that happened before, this bit publicly, extremely boldly, and correctly, predicts the eventual fate of the Nazis. Not once in this entire story has the narrator expressed surprise at this progression of events, or given any other indication it is in any way unlikely. The narrator, and the author through him, seems to be saying this is just the way it goes with tyranny, when a society has lost too much of its strength to fight off the bestial attacks of the lowly. I have omitted not just many smaller elements of the story but also a huge number of allusions to ancient history, (German) literature and especially the Bible. I imagine Jünger put them there as prizes for the few who would find them. This is one of the ways that I think On the Marble Cliffs is Ernst Jünger’s Unsong: a vehicle that lets a prolific nonfiction author
DeepNostalgia

DeepNostalgia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 12, 2021 and April 12, 2021. The archive places it in contexts such as "DeepNostalgia is a technology for “animating your family photos”". It most often appears alongside A Whirlwind Tour Of Ethereum Finance, Agan, Air Force Chapel.

Reference entry
DeepNostalgia
Mention count
1
Issue count
1
First seen
April 12, 2021
Last seen
April 12, 2021
April 12, 2021 · Original source
19: DeepNostalgia is a technology for “animating your family photos” (though critics note it just makes plausible guesses and doesn’t necessarily look like the real person). Here’s a test example with famous abolitionist Frederick Douglass:
DeLorean

DeLorean is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "gull-wing doors found on some high-end cars like the DeLorean". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
DeLorean
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
We took that kernel of an idea back and worked up forty or fifty design concepts to solve the problem, and I think we ended up with one of the most radical ones.” The Model X has what Musk coined as “falcon-wing doors.” They’re hinged versions of the gull-wing doors found on some high-end cars like the DeLorean. The doors go up and then flop over in a constrained enough way that the Model X won’t rub up against a car parked close to it or hit the ceiling in a garage. The end result is that a parent can plop a child in the second-row passenger seat without needing to bend over or twist at all.
Desoxyn

Desoxyn is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "Desoxyn to the last column"; "Desoxyn is methamphetamine. The FDA and DEA discourage doctors from prescribing it"; "less scared of prescribing Desoxyn". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
Desoxyn
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
Desoxyn is the undisputed king of the patient rating websites. Here's the same graph as before, except I've added Desoxyn to the last column:
These are some amazing numbers. Adderall itself usually has one of the highest ratings of the thousands of drugs on the site, Dexedrine beats Adderall handily, and Desoxyn wipes the floor with Dexedrine (except on WebMD, which has the smallest sample size). This drug is getting ratings that shouldn't even be possible. And the patient summaries are in line with this - here are a few:
I have been on every derivative and variation of stimulant, SSNRis SSRI, Tricyclics, beta blockers and all sorts of combinations of above and never have come across such an amazing compound. as Desoxyn. I think that there is a definable difference in mood thoughts and the way thoughts flow with memory and with present day crises.
Dextromethorphan

Dextromethorphan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 20, 2021 and August 20, 2021. The archive places it in contexts such as "DXM as a cough syrup". It most often appears alongside ACT/SSC, aducanumab, aducanumab.

Reference entry
Dextromethorphan
Mention count
1
Issue count
1
First seen
August 20, 2021
Last seen
August 20, 2021
August 20, 2021 · Original source
You see, Axsome thought they were in a good place, as did the stock market. Axome had a drug, bupropion-dextromethorphan, which had done well in their phase 3 trials for major depressive disorder. The next step after that is to submit the drug for approval to the FDA, which, when there are such clear indications of improvement, is usually a layup. An annoying layup, filled with lots of paperwork, but a layup.
Bupropion-dextromethorphan is an interesting case, because both bupropion and dextromethorphan alone are FDA-approved medications (bupropion as an antidepressant, DXM as a cough syrup). Then someone (maybe Axsome) did some preliminary studies suggesting that both of them together worked much better for depression than bupropion alone.
It’s actually weirder than that, because probably Axsome will have to charge really high prices for their combo drug to recoup the cost of the FDA approval process. Doctors will still have the alternative option of prescribing (very cheap) bupropion and dextromethorphan separately and telling the patient to take one of each. And yet Axsome is full of smart businesspeople who have assured their CEO that nobody will do this, and I’m sure those businesspeople are right. Why make patients take two cheap pills instead of one convenient super-expensive pill, when Yagmuk is paying the bills either way?
diapers.com

diapers.com is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 08, 2021 and November 08, 2021. The archive places it in contexts such as "Marc Lore founded diapers.com". It most often appears alongside America, Apolo Group, Ashkenazi.

Reference entry
diapers.com
Mention count
1
Issue count
1
First seen
November 08, 2021
Last seen
November 08, 2021
  • 21 November 08, 2021
November 08, 2021 · Original source
Bloomberg: The Diapers.com Guy Wants To Build A Utopian Megalopolis
Marc Lore founded diapers.com and various other internet startups, served a stint as Wal-Mart’s e-commerce director, and made a few billion dollars. Now he wants to start a city in the deserts of the American West, with a new vision of socially responsible democracy.
diazepam

diazepam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "the -pam at the end of benzo names (eg “diazepam”)". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
diazepam
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
— Zutano (whose name makes them sound like another novel drug in this class!) debunks my urban legend that the -pam at the end of benzo names (eg “diazepam”) stands for positive allosteric modulator:
I'm gonna go with urban legend for this one. The early benzos look to me to be chemically named; "azepine" is the word for a 7-membered ring made up of 6 carbon atoms and 1 nitrogen, then "diazepine" is the same but with two nitrogens. The first benzo was chlordiazepoxide (Librium), which if you look at the chemical structure on wikipedia, contains chlorine, diazepine and oxide (the oxygen atom). Then next is diazepam, which to me looks like "diazepine" plus "amide" (which is the word for "double-bonded oxygen atom with a nitrogen next door"). 10 years later we get alprazolam, which looks like it was named after the triazole ring (that's the 5-membered ring with 3 nitrogens), but now the "am" suffix is starting to become generic, to emphasise that its still in the same chemical class as the previous -azepams.
Dick Taylor

Dick Taylor is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "#2 Dick Taylor of California". It most often appears alongside Alinea, Alp Blossom, Alpha Tolman.

Reference entry
Dick Taylor
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Which country has the world’s best health system? This is the type of question I usually love. I rank everything. I rank the 10 best meals I’ve ever had (#1 Alinea in Chicago, #2 Tanja Grandits in Basel, and #3 OCD in Tel Aviv). I rank chocolates (#1 Askinosie, #2 Dick Taylor of California, and #3 Fruition of New York. I rank Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom). I rank colleges. I rank academic departments of bioethics and health policy that compete with my own. I rank the meals I cook, the races I run, the bike rides I take, the speeches I give.
DigitalOcean

DigitalOcean is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "I can put it up for permanent categorization, linking and eventual mirroring on a website. All I need is money to keep DigitalOcean instances up for a long, LONG time". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
DigitalOcean
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#11: Preserve And Categorize Web Fiction I'm Makin, and I'm looking for a tiny amount of funding to save the world of web fiction from the ravages of time, with a focus on rational/ist/EA fiction. So much of the history of the genre is hard to reach, and I can put it up for permanent categorization, linking and eventual mirroring on a website. All I need is money to keep DigitalOcean instances up for a long, LONG time, though I'm also looking at IPFS as an option (and if you're aware of any better fits, I welcome advice!). My last project was Homestuck.net, a pretty complete archive of the best works of the Homestuck fandom, which has taught me the necessary steps to archive and display things for future humans to use long-term. I also started the initiative to revamp the r/rational wiki so it was actually usable. If my archival project sounds good to you, I'm looking for yearly Patreon pledges at patreon.com/makin. You can reach me at makin@protonmail.com if a funny-looking Patreon is not an option or want more details about how your money will be used.
Dilberito

Dilberito is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 16, 2026 and January 16, 2026. The archive places it in contexts such as "His next venture (c. 1999) was the Dilberito"; "His next venture (c. 1999) was the Dilberito, an attempt to revolutionize food via a Dilbert-themed burrito". It most often appears alongside Adams, Alice, All-Seeing Eye.

Reference entry
Dilberito
Mention count
1
Issue count
1
First seen
January 16, 2026
Last seen
January 16, 2026
January 16, 2026 · Original source
Okay, “I am cleverer than everyone else”, got it. His next venture (c. 1999) was the Dilberito, an attempt to revolutionize food via a Dilbert-themed burrito with the full Recommended Daily Allowance of twenty-three vitamins. I swear I am not making this up. A contemporaneous NYT review said it “could have been designed only by a food technologist or by someone who eats lunch without much thought to taste”. The Onion, in its twenty year retrospective for the doomed comestible, called it a frustrated groping towards meal replacements like Soylent or Huel, long before the existence of a culture nerdy enough to support them. Adams himself, looking back from several years’ distance, was even more scathing: “the mineral fortification was hard to disguise, and because of the veggie and legume content, three bites of the Dilberito made you fart so hard your intestines formed a tail.”
Adams was 58 when Trump changed everything. In 2001, age 44, he’d found the failure of his Dilberito funny. But in another interview, at age 50, he suggested that maybe his competitors had formed teams to sneak into supermarkets and hide them in the back of the shelves. Being tragically flawed yet also self-aware enough to laugh about it is a young man’s game.
Diphenhydramine

Diphenhydramine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 12, 2021 and May 12, 2021. The archive places it in contexts such as "Diphenhydramine, one of those risky, tolerance-building sleeping pills". It most often appears alongside Alexander Pope, CBT-i, Cognitive Behavioral Therapy For Insomnia.

Reference entry
Diphenhydramine
Mention count
1
Issue count
1
First seen
May 12, 2021
Last seen
May 12, 2021
May 12, 2021 · Original source
Right now, in the heady youth of the industry, I feel angry about prescription-gated apps that cost $899. CBT-i is so good, and so important, and we were so close to being able to make it accessible to everyone. Then we snatched defeat from the jaws of victory. Getting your CBT-i will remain as financially and logistically inaccessible as everything else in medicine. Diphenhydramine, one of those risky, tolerance-building sleeping pills we want patients to avoid, is sold over-the-counter at every drugstore for a few cents a pill. But if you want to learn how to get good sleep naturally with no side effects, you’re out of luck unless you have the resources and willpower to hunt down an in-network doctor and beg them for permission.
DNP

DNP is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 02, 2021 and March 02, 2021. The archive places it in contexts such as "DNP is a mitochondrial uncoupling agent... a weight-loss pill which really works". It most often appears alongside 1938 FDA, 2,4-dinitrophenol, 2,4-dinitrophenol.

Reference entry
DNP
Mention count
1
Issue count
1
First seen
March 02, 2021
Last seen
March 02, 2021
March 02, 2021 · Original source
In the 1930s, a shady outfit called Isabella Laboratories made a popular over-the-counter diet pill called Formula 281 (slogan: "281 for the too weighty one"). If you're familiar with any of: the 1930s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?". Actually, no! It contained 2,4-dinitrophenol, a mitochondrial uncoupling agent.
So after 1938, US dieters stopped using 2,4-dinitrophenol. It next shows up in history books on the Eastern Front of World War 2, where Soviet soldiers would - I can’t believe I’m writing this - take it to keep warm. There’s something quintessentially Russian about this, like a cross between the Platonic essences of AK-47s and Krokodil. Still, World War 2 ended and poor DNP vanished from the history books again.
Whenever British tabloids, Vice, and the FDA all hate a thing, I’m inclined to feel at least a little fondness towards it. So is there a case for 2,4-dinitrophenol? I think the case would look like: sure, it has a very low therapeutic index. Sure, if you take just a few times the recommended dose, you could die. But if you very carefully take exactly the recommended dose, you probably won’t. You could give it out like methadone, in a way that makes it impossible to overdose. Patients might still get cataracts. But cataracts are treatable, or at least more treatable than some of the complications of obesity.
Doc Martens

Doc Martens is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 23, 2021 and August 23, 2021. The archive places it in contexts such as "I will be in scuffed white doc martens". It most often appears alongside 1002 N St. NW, Washington DC, 20001, 1022 High St, Madison, 210 Ardmore Avenue.

Reference entry
Doc Martens
Mention count
1
Issue count
1
First seen
August 23, 2021
Last seen
August 23, 2021
August 23, 2021 · Original source
KITCHENER-WATERLOO, ON (RSVP) Contact: JC, blxxia[at]gmail[dot]com Time: 3:00 PM, Sunday, September 19 Location: Waterloo Park, under the Wonders of Winter sign (it's an archway over a trail near the LRT station). I will be in scuffed white doc martens. Coordinates: https://w3w.co/flopped.uses.cherub
DOGE

DOGE is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 27, 2025 and February 27, 2025. The archive places it in contexts such as "but Musk/DOGE are refusing to comply?!". It most often appears alongside /r/NootropicsDepot, @fae_dreams, @ObhishekSaha.

Reference entry
DOGE
Mention count
1
Issue count
1
First seen
February 27, 2025
Last seen
February 27, 2025
February 27, 2025 · Original source
The current status of PEPFAR is still unclear - people are theorizing that maybe Trump/Rubio ordered it restarted, but Musk/DOGE are refusing to comply?! Whatever is happening, it’s “too little, too late” and many clinics are already closed.
Or maybe one newsworthy thing will happen - a plane will fall out of the sky in a way easily linked to DOGE cuts (and not DEI?), or the tariffs will cause a recession, and then all the liberals will say “Haha, we told you that any attempt to reduce government or cut red tape or leave even the tiniest space for human freedom/progress has always been sadistic doomed attempts to loot the public square and give it to billionaires!” They’re already saying this! Everyone is just going to get more and more sure that their particular form of careening to destruction is great and that we can focus entirely on beating up on the other party, and we will never get anyone who cares about good policy ever again.
dogecoin

dogecoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 20, 2021 and May 20, 2021. The archive places it in contexts such as "I assume this is why dogecoin is up this month". It most often appears alongside 5D Chess With Multiverse Time Travel, AI X-Risk Research Podcast, Alignment Research Center.

Reference entry
dogecoin
Mention count
1
Issue count
1
First seen
May 20, 2021
Last seen
May 20, 2021
May 20, 2021 · Original source
2: For the first time since 1797, someone has used the infamous Venetian doge selection process to select an officeholder - specifically, the new moderators of not-quite-officially-affiliated-with-ACX politics discussion subreddit r/TheMotte. I assume this is why dogecoin is up this month.
Donanemab

Donanemab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "Donanemab in phase 2 and phase 3"; "similar to lecanemab or donanemab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
Donanemab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%).
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
In all mature antibodies so far, they have been attended with not-great side effects: brain swelling and bleeding, for reasons related to their difficulty crossing the BBB into brain tissue where they’re actually needed. A new generation of antibodies will cross the BBB, improving efficacy and safety. It’s frustrating that getting even to a 30% slowdown has taken as long as it has, but all of this is consistent with the model of the disease I laid out, which has strong evidence behind it, and there’s every reason to expect that a new drug (A) with an optimal epitope, similar to lecanemab or donanemab, (B) given in the early preclinical phase, 10+ years earlier than currently, and (C) with a shuttle mechanism to cross the BBB, could be very successful. The mature antibodies only have (A). There are ongoing trials combining (A)+(B) [73], [114], [115], and a shortly upcoming trial combining (B)+(C) [76], but not yet all three together. I’m optimistic about these but expect (A)+(B)+(C) to do especially well. Unfortunately, this stuff is hard, slow, and over-regulated. Which means it’s taking longer than we’d like. But my guess is we’re on the right track. Challenges translating from mouse models The researchers who developed the early Alzheimer mouse models wanted the clearest possible window into disease progression, so they turned up an amyloid gene to extreme levels far beyond those of even severe human cases. This level of amyloid was so massive that it caused cognitive deficits directly, eg without any contribution from tau. And in fact, mouse proteins work differently from human proteins, and mice do not naturally get tauopathies. So researchers increased amyloid, got cognitive deficits, and thought they were simulating Alzheimer’s. But they were actually doing something significantly different: Human patients: increased amyloid → tau → neurodegeneration and disease
Doritos

Doritos is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2021 and May 18, 2021. The archive places it in contexts such as "while I agree that Doritos isn’t going to invent special flavors to celebrate May Day". It most often appears alongside #BLM, /b/, /sp/.

Reference entry
Doritos
Mention count
1
Issue count
1
First seen
May 18, 2021
Last seen
May 18, 2021
  • #BLM 1 shared issues
  • b 1 shared issues
  • sp 1 shared issues
  • 4chan 1 shared issues
  • pol 1 shared issues
May 18, 2021 · Original source
Second, while I agree that Doritos isn’t going to invent special flavors to celebrate May Day, most of the portrayals I’ve seen of socialism in media and academia have been broadly positive. They haven’t been quite as fawning to socialists as to woke people, but overall the effect still seems pro- rather than anti-; articles like this one seem more the rule than the exception. Even when the mainstream says something mildly negative about socialism, like here, nobody would confuse it for something they’re actually against, like the border wall or something. If this is the best that the powers-that-be can do in terms of class warfare to defend their position, it’s pretty pathetic.
doxepin hydrochloride

doxepin hydrochloride is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2021 and August 08, 2021. The archive places it in contexts such as "indications for use of doxepin hydrochloride". It most often appears alongside 2013 NBC article: Drug Treatment Omegaven That Could Save Infant Lives Not Yet Approved By FDA, 9/11 trutherism, aducanumab.

Reference entry
doxepin hydrochloride
Mention count
1
Issue count
1
First seen
August 08, 2021
Last seen
August 08, 2021
August 08, 2021 · Original source
People keep asking whether I’m saying the FDA should be abolished. Let me deflect that question with a discussion on the indications for use of doxepin hydrochloride.
Both Sinequan and Silenor are the exact same chemical, doxepin hydrochloride. Basically any dose of doxepin will make you sleepy, and higher doses also decrease depression. Maximum recommended dose is 300 mg/day, so both the 6 mg Silenor dose and the 10 mg Sinequan dose are nowhere near it.
doxycycline

doxycycline is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 17, 2021 and November 17, 2021. The archive places it in contexts such as "plus the antibiotic doxycycline"; "ivermectin + doxycycline, and placebo". It most often appears alongside ACE-2 receptor, ACSH, Ahmed et al.

Reference entry
doxycycline
Mention count
1
Issue count
1
First seen
November 17, 2021
Last seen
November 17, 2021
November 17, 2021 · Original source
Click to expand. # is how many people were in the smallest relevant group (eg if there were 20 people in placebo and 10 in ivermectin, it was 10). Dose is ivermectin dose x number of days. Tested w/ is what drugs were given alongside ivermectin; compare is what drugs were in the “placebo” group (I excluded some very common things like paracetamol). %-PCR7 is what percent of patients had a negative PCR test (indicating recovery) after 7 days (though if 7 wasn’t available, I accepted anything from 6-12); the (I) and (P) are ivermectin and placebo groups. R is the ratio - green if statistically significant, red otherwise. DaysPCR is how many days it took to get a negative PCR test. Days to -sym are how many days it took symptoms to resolve. -outc is some serious negative outcome in the study, either clinical worsening, hospitalization, or death. I was inconsistent which one I chose, trying to pick whichever I thought struck a balance between high sample size and severity. Since this was almost never significant, I made it blue if it favored ivermectin and orange if it favored placebo (which it never did; there is no orange). Lowest p is the lowest p-value in the study for one of the headline results. 1o+ is whether the primary outcome was positive or not. I made this very quickly and unprincipledly and I am sure there are a lot of errors; please forgive me. Of studies that included any of the endpoints I recorded, ivermectin had a statistically significant effect on the endpoint 13 times, and failed to reach significance 8 times. Of studies that named a specific primary endpoint, 9 found ivermectin affected it significantly, and 12 found it didn’t. But that’s still pretty good. And “doesn’t affect to a statistically significant degree” doesn’t mean it doesn’t work. It might just mean your study is too small for a real and important effect to achieve statistical significance. That’s why people do meta-analyses to combine studies. And the ivmmeta people say they did that and it was really impressive. All of this is still basically what things would look like if ivermectin worked. But of course we can’t give every study one vote. We’ve got to actually look at these and see which ones are good and which ones are bad. So, God help us, let’s go over all thirty of the ivermectin studies in this top panel of ivmmeta.com. (if you get bored of this, scroll down to the section called “The Analysis”) The Studies Elgazzar et al: This one isn’t on the table above, but we can’t start talking about the others until we get it out of the way. 600 Egyptian patients were randomized into six groups, including three that got ivermectin. The ivermectin groups did substantially better: for example, 2 vs. 20 deaths in ivermectin group 3 vs. non-ivermectin group 4. There were various other equally impressive outcomes. Unfortunately, it’s all false. Some epidemiologists and reporters were able to obtain the raw data (it was password-protected, but the password was “1234”), and it was pretty bizarre. Some patients appeared to have died before the trial started; others were arranged in groups of four such that it seemed like the authors had just copy-pasted the same four patients again and again. Probably either the study never happened, or at least the data were heavily edited afterwards. You can read more here. A lot of the apparent benefit of ivermectin in meta-analyses disappeared after taking out this paper (though remember, this isn’t even on the table at the top of the post, so it doesn’t directly affect that). Since the Elgazzar debacle, a group of researchers including Gideon Meyerowitz-Katz, Kyle Sheldrake, James Heathers, Nick Brown, Jack Lawrence, etc, have been trying to double-check as many other ivermectin studies as possible. At least three others - Samaha, Carvallo, and Niaee - have similar problems and have been retracted. Those studies were all removed before I screenshotted the table above, and they’re not on there. But everybody is pretty paranoid right now and looking for fraud a lot harder than they might be in normal situations. Moving on: Chowdury et al: Bangladeshi RCT. 60 patients in Group A got low-dose ivermectin plus the antibiotic doxycycline, 56 in Group B got hydroxychloroquine (another weird COVID treatment which most scientists think doesn’t work) plus the antibiotic azithromycin. No declared primary outcome. Ivermectin group got to negative PCR a little faster than the other (5.9 vs. 7 days) but it wasn’t statistically significant (p = 0.2). A couple of other non-statistically-significant things happened too. 2 controls were hospitalized, 0 ivermectin patients were. This is a boring study that got boring results, so nobody has felt the need to assassinate it, but if they did, it would probably focus on both groups getting various medications besides ivermectin. None of these other medications are believed to work, so I don’t really care about this, but you could tell a story where actually doxycycline works great at addressing associated bacterial pneumonias, or where HCQ causes lots of side effects and that makes the ivermectin group look good in comparison, or whatever. Espitia-Hernandez et al: Mexican trial which is probably not an RCT - all it says is that “patients were voluntarily allocated”. 28 ended up taking a cocktail of low-dose ivermectin, vitamin D, and azithromycin; 7 were controls. On day ten, everyone (!) in the experimental group was PCR negative; everyone (!) in the control group was still positive. Also, symptoms in the experimental group lasted an average of three days; in the control group, more like 10. These results make ivermectin look amazingly super-good, probably better than any other drug for any other disease, except maybe stuff like vitamins for treatment of vitamin deficiency. Any issues? We don’t know how patients were allocated, but they discuss patient characteristics and they don’t look different enough to produce this big an effect size. The experimental group got a lot of things other than ivermectin, but I would be equally surprised if vitamin D or azithromycin cured COVID this effectively. It deviated from its preregistration in basically every way possible, but you shouldn’t be able to get “every experimental patient tested negative when zero control patients did” by garden-of-forking-paths alone! But this has to be false, right? Even the other pro-ivermectin studies don’t show effects nearly this big. In all other studies combined, ivermectin patients took an average of 8 days to recover; in Espitia-Hernandez, they took 3. Also, it’s pretty weird that the entire control group had positive PCRs on day 10 - in most other studies, a majority of people had negative PCRs by day 7 or so, regardless of whether they were control or placebo. Everything about this is so shoddy that I can easily believe something went wrong here. I don’t have a great understanding of this one but I don’t trust it at all. Luckily it is small and non-randomized so it will be easy to ignore going forward. I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
I’m not saying this is related, but I’m not saying it *isn’t* related either. Carvallo et al: This one has all the disadvantages of Espitia-Hernandez, plus it’s completely unreadable. It’s hard to figure out how many patients there were, whether it was an RCT or not, etc. It looks like maybe there were 42 experimentals and 14 controls, and the controls were about 10x more likely to die than the experimentals. Seems pretty bad. On the other hand, another Carvallo paper was retracted because of fraud: apparently the hospital where the study supposedly took place said it never happened there. I can’t tell if this is a different version of that study, a pilot study for that study, or a different study by the same guy. Anyway, it’s too confusing to interpret, shows implausible results, and is by a known fraudster, so I feel okay about ignoring this one. Mahmud et al: RCT from Bangladesh. 200 patients received ivermectin plus doxycycline, 200 received placebo. Everything was written up very nicely in real English, by people who were clearly not on 34 lbs of meth at the time. They designated a primary outcome, “number of days required for clinical recovery”, and found a statistically significant difference at p < 0.001: Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Okay, fine, they misspelled “recovery” once. But they spelled it right the other time! That puts it in the top 50% for ivermectin papers! The fraud-hunters have examined this paper closely and are unable to find any signs of fraud. @PubPeer on the Mahmud trial of ivermectin in covid patients.\n\nI have now reviewed the individual patient data master sheet.\n\nI did not find any irregularities and the summary data matches the published data.\n\n","username":"K_Sheldrick","name":"Kyle Sheldrick","profile_image_url":"","date":"Sat Jul 17 11:06:25 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":12,"impression_count":0,"expanded_url":{"url":"https://pubpeer.com/publications/E1D65711EF28D14517731BEACB89C8#2","title":"PubPeer - Ivermectin in combination with doxycycline for treating COVI...","description":"There are comments on PubPeer for publication: Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial (2021)","domain":"pubpeer.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I think this paper is legitimate and that its findings need to be seriously considered. Serious consideration doesn’t always meant they’re true - sometimes if we have strong evidence otherwise we can dismiss things without understanding why. And there’s always the chance it was a fluke, right? Can something have a p-value less than 0.001 and still be a fluke? Szenta Fonseca et al: This is a chart review from Brazil. Researchers looked at various people who had been treated for COVID in an insurance company database, saw whether they got ivermectin or not, and saw whether the people who got it did better or worse. About a hundred people got it, and a few hundred others didn’t. The people who got it did not do any better than anyone else, and you’ll notice this is one of the rare red boxes on the table above. But we shouldn’t take this study seriously. Nobody took any effort to avoid selection bias, so it’s very possible that sicker people were given more medication (including ivermectin), which unfairly handicaps the ivermectin group. Also, it’s hard to tell from the paper who was on how much of what, and the discussion of ivermectin seems like kind of an afterthought after discussing lots of other meds in much more depth. This is another one I feel comfortable ignoring. Cadegiani et al: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . But the trial is under suspicion, with a BMJ article calling it “[the worst] violations of medical ethics and human rights in Brazil’s history” and “an ethical cesspit of violations”. [update 2022: this section originally contained more accusations against Cadegiani. Alexandros Marinos does a deeper dive with information not available at the time I wrote this, and finds some of them were overstated or false by implication] Anyway, let’s not base anything important on the results of this study, mmkay? A defiant Flavio Cadegiani. Imagine a guy who looks like this telling you to take ultra-high-dose antiandrogens. Ahmed et al: And we’re back in Bangladesh. 72 hospital patients were randomized to one of three arms: ivermectin only, ivermectin + doxycycline, and placebo. Primary endpoint was time to negative PCR, which was 9.7 days for ivermectin only and 12.7 days for placebo (p = 0.03). Other endpoints including duration of hospitalization (9.6 days ivermectin vs. 9.7 days placebo, not significant). This looks pretty good for ivermectin and does not have any signs of fraud or methodological problems. If I wanted to pick at it anyway, I would point out that the ivermectin + doxycycline group didn’t really differ from placebo, and that if you average out both ivermectin groups (with and without doxycycline) it looks like the difference would not be significant. I had previously committed to considering only ivermectin alone in trials that had multiple ivermectin groups, so I’m not going to do this. I can’t find any evidence this trial was preregistered so I don’t know whether they waited to see what would come out positive and then made that their primary endpoint, but virological clearance is a pretty normal primary endpoint and this isn’t that suspicious. It’s impossible to find any useful commentary on this study because Elgazzar (the guy who ran the most famous fraudulent ivermectin study) had the first name Ahmed, everyone is talking about Elgazzar all the time, and this overwhelms Google whenever I try to search for Ahmed et al. For now I’ll just keep this as a mildly positive and mildly plausible virological clearance result, in the context of no effect on hospitalization length or most symptoms. Chaccour et al: 24 patients in Spain were randomized to receive either medium-dose ivermectin or placebo. The primary outcome was percent of patients with negative PCR at day 7; secondary outcomes were viral load and symptoms. The primary endpoint ended up being kind of a wash - everyone still PCR positive by day 7 so it was impossible to compare groups. Ivermectin trended toward lower viral load but never reached significance. Weirdly, ivermectin did seem to help symptoms, but only anosmia and cough towards the end (p = 0.03), which you would usually think of as lingering post-COVID problems. The paper says: Given these findings, consideration could be given to alternative mechanisms of action different from a direct antiviral effect. One alternative explanation might be a positive allosteric modulation of the nicotinic acetylcholine receptor caused by ivermectin and leading to a downregulation of the ACE-2 receptor and viral entry into the cells of the respiratory epithelium and olfactory bulb. Another mechanism through which ivermectin might influence the reversal of anosmia is by inhibiting the activation of pro-inflammatory pathways in the olfactory epithelium. Inflammation of the olfactory mucosa is thought to play a key role in the development of anosmia in SARS-CoV-2 infection This seems kind of hedge-y. If you’re wondering where things went from there, Dr. Chaccour is now a passionate anti-ivermectin activist: @Finneganporter in @BusinessInsider \n\nThe roots of #ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm\n\n","username":"carlos_chaccour","name":"Dr. Carlos Chaccour ??????","profile_image_url":"","date":"Sun Nov 07 18:40:28 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":2,"like_count":9,"impression_count":0,"expanded_url":{"url":"https://www.businessinsider.in/international/news/the-roots-of-ivermectin-mania-how-south-america-incubated-a-fake-medicine-craze-that-took-the-us-by-storm/articleshow/87554081.cms","image":"https://bucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com/public/images/88d08e70-c9e2-46d4-a5df-96807b6c3a13_2000x1000.jpeg","title":"The roots of ivermectin mania: How South America incubated a fake-medicine craze that took the US by storm","description":"The popularity of unproven anti-parasitic drug ivermectin as a COVID-19 treatment is surging. Its use has roots in South America, where it was hyped by populist","domain":"businessinsider.in"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> So I guess he must think of this trial as basically negative, although realistically it’s 24 people and we shouldn’t put too much weight on it either way. Ghauri et al: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. I can’t find anyone else talking about this one. At least no one seems to be saying anything bad. Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”, because that’s really fun to say. This was a Nigerian RCT comparing 21 patients on low-dose ivermectin, 21 patients on high-dose ivermectin, and 20 patients on a combination of lopinavir and ritonavir, a combination antiviral which later studies found not to work for COVID and which might as well be considered a placebo. Primary outcome, as usual, was days until a negative PCR test. High dose ivermectin was 4.65 days, low dose was 6 days, control was 9.15, p = 0.035. Figure 2 is apparently a photograph of the computer screen where they did this calculation. Gideon Meyerowitz-Katz, part of the team that detects fraud in ivermectin papers, is not a fan of this one: He doesn’t say there what means, but elsewhere he tweets this figure: It’s always a bad sign when your study features in an image with “NUMEROUS IMPOSSIBLE NUMBERS” in red at the top. I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look. I’m going to be slightly uncomfortable with this study without rejecting it entirely, and move on. Ravakirti et al: Here we’re in Eastern India - not exactly Bangladesh again, but a stone’s throw away from it. In this RCT patients were randomized into an ivermectin group (57) and a placebo group (58). Primary outcome was negative PCR on day 6, because doing it on day 7 like everyone else would be too easy. As with several other groups, this was a bad move; too few people had it to make a good comparison; it was 13% of intervention vs. 18% of placebo, p = 0.3. Secondary outcomes were also pretty boring, except for the most important: 4 people in the placebo group died, compared to 0 in ivermectin (p = 0.045). On the one hand, this is one outcome of many, reaching the barest significance threshold. Another fluke? Still, there are no real problems with this study, and nobody has anything to say against it. Let’s add this one to the scale as another very small and noisy piece of real evidence in ivermectin’s favor. Bukhari et al: Now we’re in Pakistan. 50 patients were randomized to low-dose ivermectin, another 50 got standard of care including vitamin D. There was no placebo, but primary outcome was number of days to reach negative PCR, which it seems hard for placebo to affect much, so I don’t care. 5 controls and 9 ivermectin patients left the hospital against medical advice and could not be followed up, which is bad but not necessarily study-ruining. They never measured their supposed primary outcome of “days to reach negative PCR” directly, but they did measure how many people had negative PCR on various days, and ivermectin had a clear advantage - for example, on day 7, it was 37/50 for IVR and only 20/50 for control. Even if we assume all the lost-to-followup patients had maximally bad-for-the-hypothesis results, that’s still a positive finding. Nobody else has much to say about this one, certainly no accusations that they’ve found anything suspicious. Keep. Mohan et al: India. RCT. 40 patients got low-dose ivermectin, 40 high-dose ivermectin, and 45 placebo. Primary outcomes were time to negative PCR, and viral load on day 5. In the results, they seem to have reinterpreted “time to negative PCR” as the subtly different “percent with negative PCR on some specific day”. High-dose ivermectin did best (47.5% negative on day 5) and placebo worst (31% negative), but it was insignificant (p = 0.3). There was no difference in viral load. All groups took about the same amount of time for symptoms to resolve. More placebo patients had failed to recover by the end of the study (6) than ivermectin patients (2), but this didn’t reach statistical significance (p = 0.4). Overall a well-done, boring, negative study, although ivermectin proponents will correctly point out that, like basically every other study we have looked at, the trend was in favor of ivermectin and this could potentially end up looking impressive in a meta-analysis. Biber et al: This is an RCT from Israel. 47 patients got ivermectin and 42 placebo. Primary endpoint was viral load on day 6. I am having trouble finding out what happened with this; as far as I can tell it was a negative result and they buried it in favor of more interesting things. In a "multivariable logistic regression model, the adjusted odds ratio of negative SARS-CoV-2 RT-PCR negative test" favored ivermectin over placebo (p = 0.03 for day 6, p = 0.01 for day 8), but this seems like the kind of thing you do when your primary outcome is boring and you’re angry. Gideon Meyerowitz-Katz is not a fan: He notes that the study excluded people with high viral load, but the preregistration didn’t say they would do that. Looking more closely, he finds they did that because, if you included these people, the study got no positive results. So probably they did the study, found no positive results, re-ran it with various subsets of patients until they did get a positive result, and then claimed to have “excluded” patients who weren’t in the subset that worked. I’m going to toss this one. Elalfy et al: What even is this? Where am I? As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable, which they mention and then ignore. From there, they follow this normal and totally comprehensible flowchart: There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table… …looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Dr. Bob’s 24-In-One Internet Nootropic

Dr. Bob’s 24-In-One Internet Nootropic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 03, 2023 and April 03, 2023. The archive places it in contexts such as "Other times it’s ... Dr. Bob’s 24-In-One Internet Nootropic". It most often appears alongside 2008 Act, ACX, Adderall.

Mention count
1
Issue count
1
First seen
April 03, 2023
Last seen
April 03, 2023
April 03, 2023 · Original source
If for some reason that doesn’t work, go to a different psychiatrist and try again. You don’t have to tell them you already tried. Since everything about ADHD diagnosis and treatment is already security theater, it’s hard to say what pill mills are doing except kind of smirking under their breath while going through the rituals - as opposed to real doctors, who go through the rituals with sincere faith. Don’t get me wrong, I do think there’s a difference here. But the regulatory state isn’t set up to say “And you have to sincerely believe in the rituals or they don’t count”. So instead they punish unrelated groups, like telepsychiatrists. See also my old post Bureaucracy As Active Ingredient. The security theater doesn’t work because it’s effective. It works because it’s inconvenient enough to weed out the less motivated fakers, and some of the remaining fakers get cold feet about lying to a nice sincere psychiatrist who seems to be trying to help them. Pill mills remove the inconvenience, and seem to be nod-and-wink cooperating with liars, so the theater stops working. The only solution is to inject some inconvenience and shame back into the process somewhere, which the DEA has chosen to do by restricting telepsychiatry. They could accomplish the same goal by making you attend your appointments naked, but I guess clothing companies have better lobbyists than telepsychiatrists do. 4: Comments About Forcing Blind People To Fill Out Forms Before They Can Access Braille I analogized forcing patients to see an in-person doctor before they could access a teledoctor to forcing blind people to fill out forms before they could access Braille. Several blind people and their friends pitched in to say this was a real problem. For example, Mikolysz: Blind person here, this kind of thing is actually much more common than people imagine. Many government agencies (regardless of which particular government you mean) just assume that anybody who needs to fill a form can read and write print and/or lives with somebody who does. This is often a problem even when the form in question is specifically targeted at blind people. Non-governmental organizations, including those who specifically serve the blind, aren't much better at this either. This issue is slightly more pronounced in civil law countries, where what constitutes a legally-binding signature is clearly defined in law and you can't just Docusign your way out of the problem, but it exists everywhere, including the US. I literally had to file this kind of document today, while the main form could be filled electronically, I was required to attach a few extra documents, for GDPR and such, and those had to be printed, filled in by a sighted person, signed and scanned. The same problem exists with physical mail which you're required to read and respond to, but which is almost never available in an accessible form, a few exceptions like the American IRS notwithstanding. 5: Comments About My Caricature Of A Doctor Who Refuses To Prescribe Psych Drugs Because People Just Need Jesus Jon Cutchins writes: You don't want psychiatrists and liberals in general to be accused of an unreasoning hatred towards Christianity you should probably be more judicious in your use of anti-Christian tropes when describing everyone who is skeptical of mind-altering drugs. Mike writes: I’ve been a primary care nurse practitioner in the Bible Belt for 20yrs and not once have I even heard of a provider telling a patient they should substitute religion for psychiatric (or any) medication. It’s so easy for some people to throw around these tropes as if Christianity is some exotic, weird tribe with horrifying anthropological traits. On the other hand, fluxe writes: I am a young Christian--in my life, I have -been told by my PCP not to get an IUD because it carries "a significant risk of causing infertility or death" -had a pharmacist refuse to fill an old, male family friend's ulcer medication because it's also an abortifacient -been told by a therapist to discontinue the SSRI a different provider had prescribed and just trust in the man of the house the PCP wasn't even particularly Christian herself, but since all of her patients are she hadn't updated on IUDs since the scare back in the 70s. Our horrifying anthropological traits become everyone's problem--it might be worth listening to those who "throw around these tropes" so you can understand what they have to deal with Unfortunately I only mention this possibility because it’s happened to several of my patients. The best I can offer in terms of being unbiased and apolitical is to signal-boost posts like this one about overly woke therapists being another big problem. Alien on Earth writes: I generally like your writing and ideas, hell, I just re-uped for a year. However, in an otherwise near perfect post, you took a cheap shot at a steriotyped view of one religion thst is not popular amoungst coastal elites, that really detracts from your core point. "The worst-case is that you get one of those doctors who think that Psych Drugs Aren’t Real Because You Just Need Jesus, and then the patient has to keep looking until they find someone else." In my experience, it is the new age(y), non-religious, doctors who are least likely to like prescribing psyc. meds or who tend to give them at too low a dose or for too short a time. Certainly, I've found little correlation with their religion, if I even know it. The only correlation I've observed is that this perscription reluctance is, perhaps, slightly more common amongst middle career doctors. Perhaps it is more common in deep red areas, I don't know. However, even there, I would suggest, it is less due to religion, per se, than to "old fashion" "grit your teeth and bear it" thinking. I agree that there are many reasons people recommend against psychiatric drugs (a few are even good). Psychiatric drugs have lots of side effects and are clearly imperfect options, and I see people object to them more often when they think they have a perfect option as an alternative. Sometimes that option is Jesus. Other times it’s the trendy new somatic yoga reprocessing kundalini trauma dianetics therapy. Other times it’s LSD or ketamine or Dr. Bob’s 24-In-One Internet Nootropic. All of these work for some people, but not as much as the people pushing them think - which I guess is also true for psych drugs. I’m nervous about people who think they’ve found the answer and pressure people towards one alternative or another without presenting evidence. I’ve seen this happen enough in religious contexts that I think it was a fair thing to use as an example. 6: Comments About Which Part Of The Government Is Responsible For This Regulation ProfessorE writes: I’m not sure that what Scott wrote is even completely accurate. I have a relative who is an MD in this space, and it seems that the underlying problem is not the DEA but an actual law passed by Congress. Aren’t telemedicine regulations limited with respect to controlled substances by the Ryan Haight Act of 2008 U.S.C. § 829(e)… there may be interpretations of this act by the DEA and other agencies, but, where controlled substances are prescribed by means of the Internet, the general requirement is that the prescribing Practitioner must have conducted at least one in-person medical evaluation of the patient. It seems like a colossal overreach to ask an Executive Branch agency to overrule the plain text of the act. There are some exceptions, which Scott noted. A different way of looking at things was that the Executive Branch was highly responsive to the emergency situation of Covid. Now that it’s not an emergency, they are obligated to return to the legal framework that exists. Congress needs to change the law, not the DEA. The *data* from covid should be used as part of a cost-benefit analysis to determine whether it is reasonable to regulate telemedicine, and, if so, what regulations might address whatever problems arose. Followed by: Actually, Scott is even more off-base than I thought in my initial post. Apparently the DEA & DOJ are already proposing new changes to the 2008 Act (which seem like they violate the clear text of the act), but the act and the changes are summarized here: https://www.legitscript.com/2023/03/27/proposed-changes-ryan-haight/ Sounds like government is aware of the issue. See https://www.federalregister.gov/documents/2023/03/01/2023-04248/telemedicine-prescribing-of-controlled-substances-when-the-practitioner-and-the-patient-have-not-had For the actual changes that are being proposed. End of the day, this should be modified by Congress, not the agencies. Everyone should remember that the law was written in 2008. That’s 1 year after the very first iPhone and 2 years before the first iPad. Zoom didn’t exist (2011). None of the other technologies for video conferencing existed. Congress was attempting to fight opioid pill-mills. At the time of passage, I am willing to bet that ≈0% of patients were “Telehealth” using videoconferencing. More like phone calls and email a few times to get drugs. The law should have been amended, and it hasn’t been, but it is far from clear that it was a crazy law in the first place. I mostly accept this correction, although I’m still a bit confused - a lot of the analyses by lawyers I read said things like “Unquestionably, the DEA’s proposal is not what most industry stakeholders were anticipating. The initial reaction is the rules are more restrictive than necessary and impose concerning limitations and burdens on clinicians and the patients they treat”, and I’m confused why industry stakeholders weren’t anticipating it if the DEA had to do it in order to follow the law. And JR writes: Meanwhile, the DEA was instructed by law in -2008- to develop a special registration process for telemedicine to allow providers to prescribe controlled substances remotely. The DEA has simply failed to do so in that time, despite repeated Congressional demands to act. Don't worry, though - the DEA has said about this proposed rule that it feels this will be 'less burdensome' for providers than any kind of special registration, so it feels it has discharged its legal responsibility to create a special registration process. I am a psychiatrist having to deal with this idiocy with my patients too, and renting an office temporarily is not going to cut it. So I am going the letter route. I will probably a lose a reasonable chunk of patients I was prescribing controlled substances to. The only possible saving grace is that PCPs in this country are used to being asked to sign and complete all kinds of nonsense forms and documents so probably most of them will just do it with minimal fuss. I'm more concerned with the new requirement that all telemedicine scripts now have to be recorded by the prescriber with the date and time they were written, the PHYSICAL ADDRESS of the prescriber and patient at the time of the telehealth encounter, and have an explicit note on them that they are telemedicine prescriptions. I am less concerned about PCPs balking at writing an idiotic referral than I am skittish pharmacists refusing to fill scripts that they might interpret as being labeled equivalently to FAKE SCRIPT FOR DRUGSEEKERS Based on that comment and this, my best guess about what’s happening is: Congress passed restrictions on telemedicine in 2001, and asked the DEA to come up with a way that trusted providers could avoid those restrictions. Now that there is videoconferencing, etc, most people now believe those restrictions were too severe.
Dr. Nick's Cure-All Home Remedy

Dr. Nick's Cure-All Home Remedy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "for the same reason Dr. Nick's Cure-All Home Remedy has twelve different herbs". It most often appears alongside Adderall, ADHD, AHS.

Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
In the 1950s, a shady outfit called Obetrol Pharmaceuticals made a popular over-the-counter diet pill called Obetrol. If you're familiar with any of: the 1950s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?" and the answer is yes, loads of them. Obetrol was a mix of four different amphetamine salts: racemic amphetamine sulfate, dextroamphetamine sulfate, methamphetamine saccharate, and methamphetamine hydrochloride. Why did they need four different kinds of speed? I'm not sure. The uncharitable explanation is: for the same reason Dr. Nick's Cure-All Home Remedy has twelve different herbs, ie customers think things with more ingredients are better.
DraftKings

DraftKings is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2022 and December 20, 2022. The archive places it in contexts such as ""...place online sports bets on sites like DraftKings."". It most often appears alongside 7-11, AGI, AMC.

Reference entry
DraftKings
Mention count
1
Issue count
1
First seen
December 20, 2022
Last seen
December 20, 2022
December 20, 2022 · Original source
After the event happens, use the outcome to update everyone’s reputation and refine the algorithm. Superforecasting uses some of the same ideas as prediction markets - probabilistic forecasts, incentives to get the right answer, aggregation methods that favor people with good track records. In studies comparing superforecasting tournaments to small prediction markets, the superforecasting tournaments have done equally well or even slightly better. My goal with this FAQ is not to claim that prediction markets are always better than superforecasting. I think of both as part of the same revolution in forecasting technology, and would be happy with policy-makers or other important people using either. Still, I do think that each has situations where they might be a better fit than the other. Superforecasting tournaments shine on questions so far in the future that financial incentives start to lose force (for example, people are unlikely to place bets on questions about 2100, when most of them will be dead anyway). They’re also good in situations where you can’t get a big prediction market together - superforecasting scales down more gracefully, since you can identify individuals as superforecasters and consult them even in situations where you can’t get a full tournament together. Prediction markets shine in avoiding advanced manipulation attempts, in providing a single canonical answer when someone might worry that any given tournament was biased, and in aggregating the results of superforecaster tournaments with each other and with other sources. Remember that a superforecasting tournament can be considered an “expert”, like Nate Silver. So by the argument in Part 2, we should expect that a big prediction market won’t consistently be worse than any given superforecasting tournament, as long as the tournament’s answers are public knowledge. If there were ever a superforecasting tournament that consistently outperformed prediction markets, that would be a simple mispricing, people would correct it, and the market would eventually agree with the tournament. 4.5: Aren’t prediction markets gambling? Isn’t gambling bad and addictive? Yes, sort of. But most countries allow forms of gambling that aren’t too addictive and have some social value. For example, investing in stocks, or investing in commodities futures. I think prediction markets are more like this than like traditional gambling in casinos. People who want to gamble can already buy cryptocurrencies, or trade stocks on Robin Hood, or (in 20 states) place online sports bets on sites like DraftKings. All these things seem more addictive than, and have less social utility than, prediction markets. I don’t think promoting or legalizing prediction markets is going to make the gambling situation much worse than it is already - so given how useful I think they are, I think they would be net positive. People who are more concerned about the gambling aspect might want to stick to play money prediction markets, which wouldn’t have this problem. 4.6: Where does the money in prediction markets come from? That is, if "you get a dollar when the Democrats win”, who provides the dollar? In the abstract, prediction markets pair up people who want to bet on different sides of a proposition. For example, if a market says that there’s a 75% chance that the Democrats win, then they pair up someone willing to buy a share in “The Democrats win” for $0.75 with someone willing to buy a share in “The Democrats lose” for $0.25, for a total of $1 spent on these two shares. Then, when the Democrats either win or lose, the person with the correct share gets the $1. In practice it’s annoying to have to wait for someone to take the opposite side of the trade, so some people (or bots!) play “market maker” and are willing to take your bet on the assumption that someone else will come along soon to take the other side. But it’s usually safe to abstract this step away and just imagine people betting with each other, using the market as an intermediary. 4.6.1: Then why should anyone play prediction markets, when on average they’ll only break even? It seems like this is a worse deal than stocks, which tend to go up over time. Every dollar someone wins on a prediction market corresponds to someone else’s loss; in expectation; across all participants, the average gain is 0. But the stock market tends to go up over time, as businesses expand to new areas and invent new products; across all participants, the average gain is about 4% per year. So why ever invest in prediction markets instead of stocks? Whatever the theoretical answer to this question, lots of people do invest in prediction markets instead of stocks sometimes; several existing prediction markets have questions with hundreds of thousands of dollars in trading volume. You would have to ask those people why they do it. Maybe it’s because it’s fun. Or maybe it’s because they think (rightly or wrongly) that they’re above average and can make a profit. This is no different than other zero-sum games like sports betting, which attracts billions of dollars each year. The futures and commodities markets are also zero-sum, but attract billions of dollars by giving companies an opportunity to hedge risk. For example, a nickel mine might get rich if the price of nickel goes up, but go bankrupt if the price of nickel goes down. And they might prefer a predictable world where they get a small but guaranteed profit no matter what happens to nickel prices. So they bet some amount of money on commodity markets that the price of nickel will go down, and then their income is the sum of what they make from their nickel mining and from their bets - which, if they handled their hedging correctly, should be a small but guaranteed profit. Prediction markets would allow hedging of other types of risk - for example, import-export businesses might want to hedge against the risk that a protectionist politician gets elected, or tourism companies might want to hedge against a pandemic that closes international borders. These people would inject enough money into the market to subsidize sophisticated speculators. Finally, I envision that someday people who want to know the answer to specific questions can subsidize prediction markets on them. For example, the Democratic Party might subsidize a conditional market (see 5.1) about which Democratic primary candidate is most likely to win the general election. Their money would go to giving the average investor a 4% (or some other number) rate of return - although of course winners would gain more than that and losers would still lose on net. I think this is the most likely way for prediction markets to become very big. 4.6.1.1: If people use prediction markets to hedge risk, won’t that distort them? That is, suppose that an import-export business spends millions of dollars betting that Trump will win in order to hedge against his protectionist policies. Since their bets aren’t based on the real chance of Trump winning, won’t that distort the market? No. Suppose that everyone knows Trump has a 50-50 chance of winning. And suppose the import-export business, in the process of hedging risk, bids it up to 90-10. Since you know Trump has a 50-50 chance of winning, you can get rich quick by bidding it back down to 50-50. From your point of view, the import-export business is (in expectation) giving you free money. But they’re still happy to do it, because they’re hedging their risk successfully. 4.7: Aren’t a lot of the questions we care about inherently subjective or hard to measure? This is a frequent problem for prediction markets. For example, we might want to know something like “will we get human-level AI before 2050?” But how do we define “human-level AI”? If there’s an AI that’s much better than humans at most tasks, but much worse at a few, is that “human-level”? If there’s an AI that seems human-level in demos, but the team that makes it won’t let it be independently tested, should that count? If it works through some kind of Frankenstein chip that combines vat-grown brain tissue with computing machinery, is that still an “AI”? Prediction markets have found a few ways around this problem. First, many groups (for example, Metaculus) try to define their resolution criteria very carefully. A typical Metaculus question on AI sounds like this: We will thus define "an AI system" as a single unified software system that can satisfy the following criteria, all completable by at least some humans. Able to reliably pass a 2-hour, adversarial Turing test during which the participants can send text, images, and audio files (as is done in ordinary text messaging applications) during the course of their conversation. An 'adversarial' Turing test is one in which the human judges are instructed to ask interesting and difficult questions, designed to advantage human participants, and to successfully unmask the computer as an impostor. A single demonstration of an AI passing such a Turing test, or one that is sufficiently similar, will be sufficient for this condition, so long as the test is well-designed to the estimation of Metaculus Admins.
DuckDuckGo

DuckDuckGo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 06, 2022 and April 06, 2022. The archive places it in contexts such as "more search engines (including Bing and DuckDuckGo)". It most often appears alongside America, American consulate, Attorney General.

Reference entry
DuckDuckGo
Mention count
1
Issue count
1
First seen
April 06, 2022
Last seen
April 06, 2022
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
duloxetine

duloxetine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
duloxetine
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
If one of these doesn’t work, try the other. If neither of them work, and you’re feeling optimistic, you might want to try a different SSRI, maybe sertraline. If that doesn’t work, move on to second-line treatments. Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline.
Duloxetine is an SNRI, which supposedly means it might have some advantages over SSRIs, although studies are not completely clear. It might be better for patients with chronic pain, since it sometimes helps this also. I tend to avoid the other popular SNRI, venlafaxine, because it has very difficult withdrawal and no obvious advantages over duloxetine.
I haven’t really been convinced there’s much role for thyroid hormone or lithium as a main strategy for unipolar depression unless you have some special reason to want to use these (for example, lithium to make someone less suicidal, or thyroid hormone to correct hypothyroidism). Venlafaxine has high withdrawal potential and few obvious advantages over duloxetine. Desvenlafaxine, vilazodone, and vortioxetine are expensive without having obvious advantages over much cheaper drugs, and I can rarely find a use for them. The seligiline patch is more expensive than, and probably worse than, other MAOIs, so I rarely use it.
dutasteride

dutasteride is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "blocking allopregnanolone production with the 5α-reductase inhibitor dutasteride". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
dutasteride
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
An RCT (n=206) of isoallopregnanolone (sepranolone) in PMDD did not beat placebo for the primary outcome. However, blocking allopregnanolone production with the 5α-reductase inhibitor dutasteride does seem to work, in a small RCT at least.
Dynamax

Dynamax is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 28, 2021 and April 28, 2021. The archive places it in contexts such as "Nootropics Depot's Dynamax, a mixture of several fancy types of caffeine and caffeine-like chemicals". It most often appears alongside 2020 SSC nootropics survey, 852, BuyModa.

Reference entry
Dynamax
Mention count
1
Issue count
1
First seen
April 28, 2021
Last seen
April 28, 2021
April 28, 2021 · Original source
Results were generally predictable and unexciting (with one exception I'll get to soon). People thought stimulants worked better than non-stimulants, addictive substances better than non-addictive substances, and well-known mainstays better than new experimental chemicals. As on previous surveys, branded combination pills did worse than individual substances. For example, Nootropics Depot's Dynamax, a mixture of several fancy types of caffeine and caffeine-like chemicals, did significantly worse than ordinary caffeine. Nootropics Depot has a lot of smart, careful people, so I don't think they bungled the mixture. I think people just expect more out of branded products, and penalize them when they don't perform better. Since all tests were open label, I have no way of knowing how much of the results were just expectation effects.
EAGx LatAm

EAGx LatAm is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 10, 2023 and April 10, 2023. The archive places it in contexts such as "I'll be wearing an EAGx LatAm hoodie". It most often appears alongside 100 Alexander St, 10004 Jasper Ave, Edmonton, AB T5J 1R3, 11841 Wagner St, Culver City, CA.

Reference entry
EAGx LatAm
Mention count
1
Issue count
1
First seen
April 10, 2023
Last seen
April 10, 2023
April 10, 2023 · Original source
SANTIAGO DE COMPOSTELA, GALICIA, SPAIN Contact: Javier Contact Info: javier[dot]prieto[dot]set[at]gmail[dot]com Time: Saturday, April 15th, 05:00 PM Location: caféLaMorena. Rúa de San Clemente, 6, 15705 Santiago de Compostela, A Coruña. https://maps.app.goo.gl/FJ9vPnNTXcsvPx4LA. I'll be wearing an EAGx LatAm hoodie and maybe put up an ACX sign or something. Will sit outside, weather permitting, and inside otherwise. Coordinates: https://plus.codes/8CJHVFH3+M76
EGS

EGS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 22, 2022 and September 22, 2022. The archive places it in contexts such as "only EGS could do it, because the network effects are that tough to overcome". It most often appears alongside Adam Neumann, Alex Roesch, Amazon.

Reference entry
EGS
Mention count
1
Issue count
1
First seen
September 22, 2022
Last seen
September 22, 2022
September 22, 2022 · Original source
...which is exactly what Epic Games did a few years later. They've carved out a niche, but they've yet to give Steam a real run for their money. But realistically, only EGS could do it, because the network effects are that tough to overcome. Every other would-be Steam competitor I've seen (and I've seen so many I've lost count) has failed before they even started. (GOG was already established by this time FWIW, and they've remained tiny).
ELIZA

ELIZA is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2022 and June 07, 2022. The archive places it in contexts such as "if people were still using the ELIZA chatbot, I would be objecting that it has no true intelligence". It most often appears alongside Athens, Creole, DALL-E.

Reference entry
ELIZA
Mention count
1
Issue count
1
First seen
June 07, 2022
Last seen
June 07, 2022
June 07, 2022 · Original source
I want to stress, again, that this doesn’t mean Marcus is wrong. For example, if people were still using the ELIZA chatbot, I would be objecting that it has no true intelligence. I might give examples of just how stupid it is - for example, it doesn’t even keep track of where it is in a conversation, so if you say “Hello” in the middle of an hour-long conversation, it will say “Hello” right back and try to start a new conversation with you. A year later, they could easily introduce ELIZA 2.0, which can track conversation length, and if you say “Hello” in the middle of a conversation it will ask why you’re doing that. It might even be such an impressive upgrade that it does this organically, rather than adding this behavior in by hand in response to your specific complaint. But you could still justifiably say “This chatbot, while slightly less dumb, still has nothing like real human intelligence”. So I’m not saying Marcus is necessarily wrong about GPT still being at least one scientific revolution away from true intelligence (I do suspect he might be wrong, I just don’t think anything in this article proves it).
Empower

Empower is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "DC has a rideshare app called Empower that charges 20-40% less than Uber". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Reference entry
Empower
Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
9: @abio: “DC has a rideshare app called Empower that charges 20-40% less than Uber. (Drivers like it too because they keep 100% of the fare)...DC is trying to shut it down because of liability insurance. DC law requires $1 million per ride. The $1 million requirement isn’t sized to typical accidents. When $100,000 is the limit available for an insurance claim, 96% of personal auto claims settle below $100,000...Empower can offer $7 rides partly because it circumvents the mandate. DC is shutting it down for exactly that reason.”
Emsam

Emsam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 16, 2022 and November 16, 2022. The archive places it in contexts such as "recognized it as an Emsam wrapper"; "Does this mean that Emsam definitely wasn’t involved?"; "I don’t think Emsam is vastly worse than other dopaminergic drugs". It most often appears alongside @AutismCapital, Adderall, ADHD.

Reference entry
Emsam
Mention count
1
Issue count
1
First seen
November 16, 2022
Last seen
November 16, 2022
November 16, 2022 · Original source
Milky Eggs reports a claim by an employee that Sam was on “a patch for designer stimulants that mainlined them into his blood to give him a constant buzz at all times”. This could be a hyperbolic description of Emsam, a patch form of the antidepressant/antiparkinsonian agent selegiline. The detectives at the @AutismCapital Twitter account found a photo of SBF, zoomed in on a scrap of paper on his desk, and recognized it as an Emsam wrapper.
Emsam is a brand of selegiline, a medication used since the 1960s to treat Parkinson’s disease. Selegiline is a MAOB inhibitor2. MAOB is an enzyme that breaks down dopamine3. If you inhibit it, you get more dopamine. So in a very broad sense, selegiline gives you more dopamine.4
Selegiline is an even less magical bullet than usual. People call it an antidepressant, anti-Parkinsonian, and stimulant, and all of those descriptions are accurate. It also does one unrelated thing: it disables a key digestive enzyme that prevents certain foods from killing you. For boring technical reasons, some pharma companies thought this might not happen if you delivered selegiline through a patch on the skin. For other boring technical reasons, the FDA disagreed and said people on the selegiline patch still shouldn’t eat those foods. The pharma companies decided to release the patch anyway, in case some people liked patches better than pills - and so Emsam was born.
Enovid

Enovid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 04, 2024 and April 04, 2024. The archive places it in contexts such as "Enovid, a promising treatment for respiratory infections like colds and COVID". It most often appears alongside Aaron Peskin, ACLU, AGI And The Efficient Market Hypothesis.

Reference entry
Enovid
Mention count
1
Issue count
1
First seen
April 04, 2024
Last seen
April 04, 2024
April 04, 2024 · Original source
27: Elizabeth (AcesoUnderGlass) reviews nitric oxide nasal spray / “Enovid”, a promising treatment for respiratory infections like colds and COVID (you spray the nitric oxide in your nasal passages, and it kills the viruses). I use this, but not enough to feel like I have an opinion on how well it works.
EpiPen

EpiPen is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 20, 2021 and August 20, 2021. The archive places it in contexts such as "FDA rejected an EpiPen competitor for “certain major deficiencies”". It most often appears alongside ACT/SSC, aducanumab, aducanumab.

Reference entry
EpiPen
Mention count
1
Issue count
1
First seen
August 20, 2021
Last seen
August 20, 2021
August 20, 2021 · Original source
The word “deficiencies” rings a bell, because I remember the FDA rejected an EpiPen competitor for “certain major deficiencies” without giving more information (at least not to the public). EpiPen took advantage of this to quadruple their prices, although the FDA did eventually approve the competitor a few years later. I was never able to figure out what the “deficiencies” were, which is too bad, because there seems to be something of an epidemic of “deficiencies” at the FDA these days.
esketamine

esketamine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2021 and August 08, 2021. The archive places it in contexts such as "thinking of esketamine, which is worse and costs 25x as much". It most often appears alongside 2013 NBC article: Drug Treatment Omegaven That Could Save Infant Lives Not Yet Approved By FDA, 9/11 trutherism, aducanumab.

Reference entry
esketamine
Mention count
1
Issue count
1
First seen
August 08, 2021
Last seen
August 08, 2021
August 08, 2021 · Original source
I want a world where if everyone knows ketamine is a great depression treatment, if I’ve been blogging about the intricacies of ketamine depression treatment for years - then ketamine eventually gets approved for use as a depression treatment (it still isn’t - if you think it is, you’re probably thinking of esketamine, which is worse and costs 25x as much).
etifoxine

etifoxine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 28, 2023 and September 28, 2023. The archive places it in contexts such as "Alex Kesin makes the case for etifoxine, a French anxiety drug which is like Xanax but safer". It most often appears alongside 2020 election, @eigenrobot, @jeremychrysler.

Reference entry
etifoxine
Mention count
1
Issue count
1
First seen
September 28, 2023
Last seen
September 28, 2023
September 28, 2023 · Original source
20: Alex Kesin makes the case for etifoxine, a French anxiety drug which is like Xanax but safer, and discusses our prospects of ever getting it in the US.
Etsy

Etsy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 16, 2026 and January 16, 2026. The archive places it in contexts such as "Contra current ideological fault lines, where these tendencies bring up images of Etsy witches". It most often appears alongside Adams, Alice, All-Seeing Eye.

Reference entry
Etsy
Mention count
1
Issue count
1
First seen
January 16, 2026
Last seen
January 16, 2026
January 16, 2026 · Original source
And the Nineties (God’s Debris was published in 2001) were a special time. The decade began with the peak of Wicca and neopaganism. Contra current ideological fault lines, where these tendencies bring up images of Etsy witches, they previously dominated nerd circles, including male nerds, techie nerds, and right-wing nerds (did you know Eric S. Raymond is neopagan?) By decade’s end, the cleverest (ie most annoying) nerds were switching to New Atheism; throughout, smaller groups were exploring Discordianism, chaos magick, and the Subgenius. The common thread was that Christianity had lost its hegemonic status, part of being a clever nerd was patting yourself on the back for having seen through it, but exactly what would replace it was still uncertain, and there was still enough piety in the water supply that people were uncomfortable forgetting about religion entirely. You either had to make a very conscious, marked choice to stop believing (New Atheism), or try your hand at the task of inventing some kind of softer middle ground (neopaganism, Eastern religion, various cults, whatever this book was supposed to be).
Evekeo

Evekeo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "Evekeo takes Adderall's questionable decision to include l-amphetamine and doubles down on it"; "I might try Evekeo". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
Evekeo
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
Evekeo takes Adderall's questionable decision to include l-amphetamine and doubles down on it. Remember, Dexedrine is 100% d-amphetamine and Adderall is 75% d, 25% l. Well, Evekeo is 50-50. This should make it strictly worse than Adderall, and my patients' feedback seems to agree with this. The supposed point of making it is those studies that show a small subgroup of people seem to get some extra benefit from l-amphetamine. The real point of making it is probably as a me-too drug; it doesn't require any research, since l-amphetamine and d-amphetamine have both been around forever, but since it's new and different you can charge a lot of money for it.
I can't think of any situation where it would be reasonable to prescribe Evekeo as a first-line stimulant. If someone has done sort of okay on Adderall but has lots of side effects, and you put them on Dexedrine and they get worse instead of better, I suppose you could try putting them on Evekeo to see if they really are in the small subgroup of l-amphetamine beneficiaries. I'm just annoyed that this relatively rare legitimate use case serves a fig leaf for the inevitable Big Pharma campaign to push this new on-patent very expensive medication on a bunch of people who don't need it.
When I treat ADHD with amphetamines, I usually start with Adderall/extended release Adderall, even though realistically Dexedrine would probably be an equally good or better choice. If it's not working very well or there are too many side effects, I switch to Dexedrine/extended release Dexedrine. If Dexedrine doesn't work because it seems too strong or the patient "crashes" too hard afterwards, or if I'm worried the patient is at risk of addiction, I will try Vyvanse (or some other solution to stimulant “crashes”); if Dexedrine works less well than Adderall and I am very confused and the patient is in an experimenting kind of mood, I might try Evekeo. If none of these work, a braver person than I am might try Desoxyn. As for me, I give up on amphetamines and start looking at Ritalin, modafinil, or other options.
Even Mind

Even Mind is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "Our app, Even Mind, takes a different approach that avoids recall bias altogether". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Reference entry
Even Mind
Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#86: More Accurate Measurement Of Mental Health Even Mental Health is a startup working on improving how we measure mental health. Current approaches rely on asking individuals to summarize how they’ve felt in the past. This yields a blurry and often inaccurate depiction of one’s mental health. Our app, Even Mind, takes a different approach that avoids recall bias altogether (you can find out more at https://evenmind.app). We believe more accurate measurement tools will lead to significantly improved treatments and outcomes for individuals. We’re looking to connect with others interested in improving mental health measurement or mental healthcare more broadly. We’re also raising an initial round and looking for investments in the $50,000 - $100,000 range. If you’d like to connect, please email me at cwoods@evenmind.co.
Excel

Excel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2024 and September 18, 2024. The archive places it in contexts such as "Sometimes Excel inappropriately converts things to dates". It most often appears alongside AIDER, Ajeya Cotra, Alan Turing.

Reference entry
Excel
Mention count
1
Issue count
1
First seen
September 18, 2024
Last seen
September 18, 2024
September 18, 2024 · Original source
All these milestones have fallen in the most ambiguous way possible. GPT-4 can create excellent art and passable poetry, but it’s just sort of blending all human art into component parts until it understands them, then doing its own thing based on them. AlphaGeometry can invent novel proofs, but only for specific types of questions in a specific field, and not really proofs that anyone is interested in. AlphaFold solved the difficult scientific problem of protein folding, but it was “just mechanical”, spitting out the conformations of proteins the same way a traditional computer program spits out the digits of pi. Apparently the youth have all fallen in love with AI girlfriends and boyfriends on character.ai, but this only proves that the youth are horny and gullible.
But nobody finds this scary. Nobody thinks “oh, yeah, Bostrom and Yudkowsky were right, this is that AI safety thing”. It’s just another problem for the cybersecurity people. Sometimes Excel inappropriately converts things to dates; sometimes GPT-6 tries to upload itself into an F-16 and bomb stuff. That specific example might be kind of a joke. But thirty years ago, it also would have sounded pretty funny to speculate about a time when “everyone knows” AIs can write poetry and develop novel mathematics and beat humans at chess, yet nobody thinks they’re intelligent.
Express VPN

Express VPN is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 22, 2022 and July 22, 2022. The archive places it in contexts such as "a podcast sponsored by Express VPN". It most often appears alongside 2020 election, 2022 book review contest, 2122.

Reference entry
Express VPN
Mention count
1
Issue count
1
First seen
July 22, 2022
Last seen
July 22, 2022
July 22, 2022 · Original source
It doesn’t let up. He riffs on the Mafia, Big Pharma, false flags, faked autopsies… were he alive today, he’d be ranting about banksters and Hollywood elites on a podcast sponsored by Express VPN. But he’s working towards a point:
ExxonMobil

ExxonMobil is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 01, 2023 and March 01, 2023. The archive places it in contexts such as "some AI doomers think of OpenAI as an Exxon-Mobil style villain". It most often appears alongside AGI, AI, Anthropic.

Reference entry
ExxonMobil
Mention count
1
Issue count
1
First seen
March 01, 2023
Last seen
March 01, 2023
March 01, 2023 · Original source
Imagine ExxonMobil releases a statement on climate change. It’s a great statement! They talk about how preventing climate change is their core value. They say that they’ve talked to all the world’s top environmental activists at length, listened to what they had to say, and plan to follow exactly the path they recommend. So (they promise) in the future, when climate change starts to be a real threat, they’ll do everything environmentalists want, in the most careful and responsible way possible. They even put in firm commitments that people can hold them to.
Sam Altman posing with leading AI safety proponent Eliezer Yudkowsky. Also Grimes for some reason. Planning For AGI And Beyond (“AGI” = “artificial general intelligence”, ie human-level AI) is the latest volley in that campaign. It’s very good, in all the ways ExxonMobil’s hypothetical statement above was very good. If they’re trying to fool people, they’re doing a convincing job! Still, it doesn’t apologize for doing normal AI company stuff in the past, or plan to stop doing normal AI company stuff in the present. It just says that, at some indefinite point when they decide AI is a threat, they’re going to do everything right. This is more believable when OpenAI says it than when ExxonMobil does. There are real arguments for why an AI company might want to switch from moving fast and breaking things at time t to acting all responsible at time t + 1 . Let’s explore the arguments they make in the document, go over the reasons they’re obviously wrong, then look at the more complicated arguments they might be based off of. Why Doomers Think OpenAI Is Bad And Should Have Slowed Research A Long Time Ago OpenAI boosters might object: there’s a disanalogy between the global warming story above and AI capabilities research. Global warming is continuously bad: a temperature increase of 0.5 degrees C is bad, 1.0 degrees is worse, and 1.5 degrees is worse still. AI doesn’t become dangerous until some specific point. GPT-3 didn’t hurt anyone. GPT-4 probably won’t hurt anyone. So why not keep building fun chatbots like these for now, then start worrying later? Doomers counterargue that the fun chatbots burn timeline. That is, suppose you have some timeline for when AI becomes dangerous. For example, last year Metaculus thought human-like AI would arrive in 2040, and superintelligence around 2043. Recent AIs have tried lying to, blackmailing, threatening, and seducing users. AI companies freely admit they can’t really control their AIs, and it seems high-priority to solve that before we get superintelligence. If you think that’s 2043, the people who work on this question (“alignment researchers”) have twenty years to learn to control AI. Then OpenAI poured money into AI, did ground-breaking research, and advanced the state of the art. That meant that AI progress would speed up, and AI would reach the danger level faster. Now Metaculus expects superintelligence in 2031, not 2043 (although this seems kind of like an over-update), which gives alignment researchers eight years, not twenty. So the faster companies advance AI research - even by creating fun chatbots that aren’t dangerous themselves - the harder it is for alignment researchers to solve their part of the problem in time. This is why some AI doomers think of OpenAI as an Exxon-Mobil style villain, even though they’ve promised to change course before the danger period. Imagine an environmentalist group working on research and regulatory changes that would have solar power ready to go in 2045. Then ExxonMobil invents a new kind of super-oil that ensures that, nope, all major cities will be underwater by 2031 now. No matter how nice a statement they put out, you’d probably be pretty mad! Why OpenAI Thinks Their Research Is Good Now, But Might Be Bad Later OpenAI understands the argument against burning timeline. But they counterargue that having the AIs speeds up alignment research and all other forms of social adjustment to AI. If we want to prepare for superintelligence - whether solving the technical challenge of alignment, or solving the political challenges of unemployment, misinformation, etc - we can do this better when everything is happening gradually and we’ve got concrete AIs to think about: We believe we have to continuously learn and adapt by deploying less powerful versions of the technology in order to minimize “one shot to get it right” scenarios […] As we create successively more powerful systems, we want to deploy them and gain experience with operating them in the real world. We believe this is the best way to carefully steward AGI into existence—a gradual transition to a world with AGI is better than a sudden one. We expect powerful AI to make the rate of progress in the world much faster, and we think it’s better to adjust to this incrementally. A gradual transition gives people, policymakers, and institutions time to understand what’s happening, personally experience the benefits and downsides of these systems, adapt our economy, and to put regulation in place. It also allows for society and AI to co-evolve, and for people collectively to figure out what they want while the stakes are relatively low. You might notice that, as written, this argument doesn’t support full-speed-ahead AI research. If you really wanted this kind of gradual release that lets society adjust to less powerful AI, you would do something like this: Release AI #1
This would be the equivalent of ExxonMobil making a legally-binding promise to switch to environmentalist mode at the exact moment that warming passes 1.5 degrees C - maybe still a little strange, but starting to sound more-than-zero meaningful.
F-16s

F-16s is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 22, 2024 and November 22, 2024. The archive places it in contexts such as "they gave Ukraine F-16s". It most often appears alongside AI, ATACMS, Biden.

Reference entry
F-16s
Mention count
1
Issue count
1
First seen
November 22, 2024
Last seen
November 22, 2024
November 22, 2024 · Original source
Suppose something important will happen at a certain unknown point. As someone approaches that point, you might be tempted to warn that the thing will happen. If you’re being appropriately cautious, you’ll warn about it before it happens. Then your warning will be wrong. As things continue to progress, you may continue your warnings, and you’ll be wrong each time. Then people will laugh at you and dismiss your predictions, since you were always wrong before. Then the thing will happen and they’ll be unprepared. Toy example: suppose you’re a doctor. Your patient wants to try a new experimental drug, 100 mg. You say “Don’t do it, we don’t know if it’s safe”. They do it anyway and it’s fine. You say “I guess 100 mg was safe, but don’t go above that.” They try 250 mg and it’s fine. You say “I guess 250 mg was safe, but don’t go above that.” They try 500 mg and it’s fine. You say “I guess 500 mg was safe, but don’t go above that.” They say “Haha, as if I would listen to you! First you said it might not be safe at all, but you were wrong. Then you said it might not be safe at 250 mg, but you were wrong. Then you said it might not be safe at 500 mg, but you were wrong. At this point I know you’re a fraud! Stop lecturing me!” Then they try 1000 mg and they die. The lesson is: “maybe this thing that will happen eventually will happen now” doesn’t count as a failed prediction. I’ve noticed this in a few places recently. First, in discussion of the Ukraine War, some people have worried that Putin will escalate (to tactical nukes? to WWIII?) if the US gives Ukraine too many new weapons. Lately there’s a genre of commentary (1, 2, 3, 4, 5, 6, 7) that says “Well, Putin didn’t start WWIII when we gave Ukraine HIMARS. They didn’t start WWIII when we gave Ukraine ATACMS. He didn’t start WWIII when we gave Ukraine F-16s. So the people who believe Putin might start WWIII have been proven wrong, and we should escalate as much as possible.” There’s obviously some level of escalation that would start WWIII (example: nuking Moscow). So we’re just debating where the line is. Since nobody (except Putin?) knows where the line is, it’s always reasonable to be cautious. I don’t actually know anything about Ukraine, but a warning about HIMARS causing WWIII seems less like “this will definitely be what does it” and more like “there’s a 2% chance this is the straw that breaks the camel’s back”. Suppose we have two theories, Escalatory-Putin and Non-Escalatory-Putin. EP says that for each new weapon we give, there’s a 2% chance Putin launches a tactical nuke. NEP says there’s a 0% chance. If we start out with even odds on both theories, after three new weapons with no nukes, our odds should only go down to 48.5% - 51.5%. (yes, this is another version of the generalized argument against updating on dramatic events) Second, I talked before about getting Biden’s dementia wrong. My internal argument against him being demented was something like “They said he was demented in 2020, but he had a good debate and proved them wrong. They said he was demented in 2022, but he gave a good State Of The Union and proved them wrong. Now they’re saying he’s demented in 2024, but they’ve already discredited themselves, so who cares?” I think this was broadly right about the Republican political machine, who was just throwing the same allegation out every election and seeing if it would stick. But regardless of the Republicans’ personal virtue, the odds of an old guy becoming newly demented each year is about 4% per year. If it had been two years since I last paid attention to this question, there was an 8% chance it had happened while I wasn’t looking. Like the other examples, dementia is something that happens eventually (this isn’t strictly true - some people reach their 100s without dementia - but I think it’s a fair idealized assumption that if someone survives long enough, then eventually their risk of cognitive decline becomes very high). It is reasonable to be worried about the President of the United States being demented - so reasonable that people will start raising the alarm about it being a possibility long before it happens. Even if some Republicans had ulterior motives for harping on it, plenty of smart, well-meaning people were also raising the alarm. Here I failed by letting the multiple false alarms lull me into a false sense of security, where I figured the non-demented side had “won” the “argument”, rather than it being a constant problem we needed to stay vigilant for. Third, this is obviously what’s going on with AI right now. The SB1047 AI safety bill tried to monitor that any AI bigger than 10^25 FLOPs (ie a little bigger than the biggest existing AIs) had to be exhaustively tested for safety. Some people argued - the AI safety folks freaked out about how AIs of 10^23 FLOPs might be unsafe, but they turned out to be safe. Then they freaked out about how AIs of 10^24 FLOPs might be unsafe, but they turned out to be safe. Now they’re freaking out about AIs of 10^25 FLOPs! Haven’t we already figured out that they’re dumb and oversensitive? No. I think of this as equivalent to the doctor who says “We haven’t confirmed that 100 mg of the experimental drug is safe”, then “I guess your foolhardy decision to ingest it anyway confirms 100 mg is safe, but we haven’t confirmed that 250 mg is safe, so don’t take that dose,” and so on up to the dose that kills the patient. It would be surprising if AI never became dangerous - if, in 2500 AD, AI still can’t hack important systems, or help terrorists commit attacks or anything like that. So we’re arguing about when we reach that threshold. It’s true and important to say “well, we don’t know, so it might be worth checking whether the answer is right now.” It probably won’t be right now the first few times we check! But that doesn’t make caution retroactively stupid and unjustified, or mean it’s not worth checking the tenth time. Can we take this insight too far? Suppose Penny Panic says “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans and it doesn’t happen. The next election cycle: “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans again and it still doesn’t happen. After her saying this every election cycle, and being wrong every election cycle, shouldn’t we stop treating her words as meaningful? I think we have to be careful to distinguish this from the useful cases above. It’s not true that, each election, the chance of Republicans becoming dictators increases, until eventually it’s certain. This is different from our examples above: Eventually at some age, Castro has to die, and the chance gets higher the older he gets.
FaceApp

FaceApp is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 01, 2022 and July 01, 2022. The archive places it in contexts such as "FaceApp morph of all Democratic Senators". It most often appears alongside @a_centrism, @amplituhedron, AISafetySupport.com.

Reference entry
FaceApp
Mention count
1
Issue count
1
First seen
July 01, 2022
Last seen
July 01, 2022
July 01, 2022 · Original source
29: Claim from the comments section: “FaceApp morph of all Democratic Senators (‘what if John Hickenlooper was a cannibal?’) and all Republican Senators (‘what if Bob Katter was the smuggest individual on the planet?’) is *extremely* evocative of Paul Fussell's chart distinguishing upper-middle from prole”.
Facebook ads

Facebook ads is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "Also on their list were Facebook ads and the Android". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Facebook ads
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
This book taught me that everyone always predicts Elon will fail at whatever he does. When he started the original X (later PayPal), everyone who knew anything about finance told him he would fail. Just because he was a hotshot coder who could write software didn’t mean he could navigate the totally-different and heavily-regulated world of finance. Elon, who started out indeed knowing nothing about finance, learned on the job and got a $200 million exit. Gawker voted Tesla #1 in their Biggest Tech Flops of 2007 (also on their list were Facebook ads and the Android . . . maybe journalists don’t actually understand tech?)
Facebook Dating

Facebook Dating is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 14, 2023 and February 14, 2023. The archive places it in contexts such as "Also Facebook Dating , although it’s (indefensibly) not available on computers and has to be accessed by cell phone". It most often appears alongside Aella, Austin, clown dating site.

Reference entry
Facebook Dating
Mention count
1
Issue count
1
First seen
February 14, 2023
Last seen
February 14, 2023
  • 23 February 14, 2023
February 14, 2023 · Original source
One solution is to piggyback off existing social media sites. There’s something called Twinder for Twitter which seems to do this correctly, though they haven’t made any posts since 2018 and I think they’re defunct. Also Facebook Dating, although it’s (indefensibly) not available on computers and has to be accessed by cell phone. But these aren’t real piggybacks; just because your crush has a Twitter account doesn’t mean they use Twinder. Facebook Dating makes the interesting decision to, if you register a crush on someone, send them a Facebook message saying that an anonymous person likes them and they should try getting Facebook Dating; I can’t decide whether this is a necessary evil, or if it violates the principle of not imposing emotional costs on people who don’t want them.
Falcon 1

Falcon 1 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "used to steer the upper stage of Falcon 1"; "practical suggestions to get the Falcon 1 out the door more quickly"; "and the Falcon 1 kept blowing up". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Falcon 1
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
SpaceX needed an actuator that would trigger the gimbal action used to steer the upper stage of Falcon 1. Davis had never built a piece of hardware before in his life and naturally went out to find some suppliers who could make an electromechanical actuator for him. He got a quote back for $120,000. “Elon laughed,” Davis said. “He said, 'That part is no more complicated than a garage door opener. Your budget is five thousand dollars. Go make it work.’” Davis spent nine months building the actuator. At the end of the process, he toiled for three hours writing an e-mail to Musk covering the pros and cons of the device. The e-mail went into gory detail about how Davis had designed the part, why he had made various choices, and what its cost would be. As he pressed send, Davis felt anxiety surge through his body knowing that he’d given his all for almost a year to do something an engineer at another aerospace company would not even attempt. Musk rewarded all of this toil and angst with one of his standard responses. He wrote back, “Ok.”
The actuator Davis designed ended up costing $3,900 and flew with Falcon 1 into space.
Employees who made detailed cases around what they saw as flaws in the Falcon 5 design or presented practical suggestions to get the Falcon 1 out the door more quickly were often ignored or worse. “The treatment of staff was not good for long stretches of this era,” said one engineer. “Many good engineers, who everyone beside ‘management’ felt were assets to the company, were forced out or simply fired outright after being blamed for things they hadn’t done. The kiss of death was proving Elon wrong about something.”
Falcon 5

Falcon 5 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "Employees who made detailed cases around what they saw as flaws in the Falcon 5 design"; "Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Falcon 5
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Employees who made detailed cases around what they saw as flaws in the Falcon 5 design or presented practical suggestions to get the Falcon 1 out the door more quickly were often ignored or worse. “The treatment of staff was not good for long stretches of this era,” said one engineer. “Many good engineers, who everyone beside ‘management’ felt were assets to the company, were forced out or simply fired outright after being blamed for things they hadn’t done. The kiss of death was proving Elon wrong about something.”
When SpaceX was on its last few hundred thousand dollars, and the Falcon 1 kept blowing up, and no private company had ever launched a rocket to space before, and they only had a few weeks to make Falcon 1 fly and restore investor confidence before the company went bankrupt - Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9. The same thing happened with the Tesla Roadster and the Model S.
Falcon Heavy

Falcon Heavy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 07, 2022 and January 07, 2022. The archive places it in contexts such as "stack them one atop the other underneath the Falcon Heavy fairing". It most often appears alongside ACX Discord, Aerojet XLR-132, Aimable.

Reference entry
Falcon Heavy
Mention count
1
Issue count
1
First seen
January 07, 2022
Last seen
January 07, 2022
January 07, 2022 · Original source
But, OK, let's assume I can design three optimized hypergolic upper stages using one, three, and nine Aerojet XLR-132 engines each and a mass fraction of 0.9, stack them one atop the other underneath the Falcon Heavy fairing, designed built and assembled in three months, and somehow the whole thing actually *works*, OK, that will boost a single W83 to 18 km/s hyperbolic excess velocity with 100 kg left over for the guidance, navigation, telemetry, and midcourse propulsion system. 18 km/s is not 20 km/s, but meh, close enough.
How do you feel about the odds of arranging eleven hundred Falcon Heavy launches, or the equivalent, on three months' notice?
FastMath Pro

FastMath Pro is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as ""Fast Math" ... mostly on 'FastMath Pro'". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
FastMath Pro
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
“Fast Math” (doing simple math they already know how to do faster and more accurately; mostly on “Rocket Math” or “FastMath Pro”)
Ferrari

Ferrari is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 12, 2025 and August 12, 2025. The archive places it in contexts such as "If I want a Ferrari, it’s going to be expensive". It most often appears alongside All Who Go Not Return, Amica Terra, Amish.

Reference entry
Ferrari
Mention count
1
Issue count
1
First seen
August 12, 2025
Last seen
August 12, 2025
August 12, 2025 · Original source
This is what I mean by “this space needs entrepreneurs”. If I want a Ferrari, it’s going to be expensive, but not complicated. Once there are expensive and effortful, but not complicated, ways to get a good community, I’ll be more willing to believe that effort is the barrier.
Ferrari 312 T4

Ferrari 312 T4 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2022 and December 20, 2022. The archive places it in contexts such as ""circa-2021 Ferrari 312 T4 1:8 scale automobile model"". It most often appears alongside 7-11, AGI, AMC.

Reference entry
Ferrari 312 T4
Mention count
1
Issue count
1
First seen
December 20, 2022
Last seen
December 20, 2022
December 20, 2022 · Original source
Has general robotic capabilities, of the type able to autonomously, when equipped with appropriate actuators and when given human-readable instructions, satisfactorily assemble a (or the equivalent of a) circa-2021 Ferrari 312 T4 1:8 scale automobile model. A single demonstration of this ability, or a sufficiently similar demonstration, will be considered sufficient.
Ferraris

Ferraris is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2022 and September 13, 2022. The archive places it in contexts such as "predicted rewards like Ferraris". It most often appears alongside Andres, bereavement, companionate love.

Reference entry
Ferraris
Mention count
1
Issue count
1
First seen
September 13, 2022
Last seen
September 13, 2022
September 13, 2022 · Original source
What about March 1? Suppose you do a few specific things - you buy a Ferrari, drive it around, and eat dinner in the fanciest restaurant in town. Do you enjoy these things? Presumably yes. Why? You knew all throughout February that you were planning to get a Ferrari and a fancy dinner today. And you knew that Ferraris and fancy dinners were pleasant; otherwise you wouldn’t have gotten them. So how come predicting you would get the money mostly cancels out the goodness of getting the money, but predicting you would get the Ferrari/dinner doesn’t cancel out the goodness of the Ferrari/dinner?
Another possibility is to say you can never predict away all reward - sort of like how even after your spouse has been dead for weeks, your brain still hasn’t fully adjusted its “predictions”. This would also match an “active inference” theory of drives, where the body implements hunger by something like a non-update-able prediction that you’re well-fed, and then lets you be unhappy about the “prediction error” and work to fix it. Maybe some lingering happiness from things like good relationships come from an inability to update the last little bit of the “I am not in a good relationship” prediction, added specifically as a hack so that people in good relationships can still be happy. But I don’t think this matches the neuroscientific evidence; you can just check the reward center for simple things (traditionally a monkey drinking juice) and find that it’s fully adjusted away this prediction (even though the monkey presumably enjoys the juice just as much as we enjoy our predicted rewards like Ferraris.)
Firefox

Firefox is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 28, 2021 and February 28, 2021. The archive places it in contexts such as "Available for Firefox and Chrome". It most often appears alongside ACX reader Pycea, Chrome, India.

Reference entry
Firefox
Mention count
1
Issue count
1
First seen
February 28, 2021
Last seen
February 28, 2021
February 28, 2021 · Original source
5: Substack still claims to be working on fixing some of the comment problems on their end, though I don’t have an ETA or progress reports to give you. While you’re waiting, ACX reader Pycea has created a browser extension which fixes some remaining issues with the comments section here, including auto-expanding everything, highlighting new comments, hiding hearts, and several other things. Available for Firefox and Chrome, with some partial fixes for Safari available here. Thanks, Pycea!
Firestone

Firestone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 10, 2022 and May 10, 2022. The archive places it in contexts such as "now works for Firestone". It most often appears alongside A Few Good Men, Adolf Eichmann, Akron.

Reference entry
Firestone
Mention count
1
Issue count
1
First seen
May 10, 2022
Last seen
May 10, 2022
May 10, 2022 · Original source
The mediocre develop faster than either the talented or the untalented An alternative way of looking at these three laws is to note that defense mechanisms emerge to sustain addictions even when the developmental environment that originally nourished it vanishes. Defense mechanisms though, are more useful as a partial catalog of phenomenology than as a foundational idea. These then are the developmental psychology roots of the Gervais Principle. Recall that Cluelessness goes with overperformance. That overperformance is caused by arrested development around a strength, which has been hooked by an addictive environment of social rewards. Mediocrity is your best defense against addiction, and guarantor of further open-ended psychological development. And yes, for the alert among you who have spotted a connection, arrested development is the dark side of strengths in the sense of Positive Psychology. A strength in one situation is merely an entrenched piece of arrested development in another. In our model, the three development stages – Clueless, Losers and Sociopaths – correspond to different patterns of arrested development and different strength-addictions. That is, development involves progressing from one stage (eg school) to another stage (eg the real world). But if you’re too good at an early stage, you become accustomed to the reward you get from success. Suppose you loved school and did great at it. Then you get invited to participate in the real world, a noticeably non-school-like environment. You try it, and instead of getting praise/reward/validation all the time, you get those things rarely or not at all. If you can, maybe you go back to school (ie get a PhD), a strategy with problems of its own. But if you can’t real-world actually go back to school, instead you might remain permanently stuck at a psychological stage where everything feels like school, where you try to distort your perceptions until your world-model looks vaguely school-like, and where you use your school-based skills and coping mechanisms for everything. The particular example I just gave, about school, is Rao’s explanation for Dwight Schrute: Dwight, with his stern German upbringing, lacked the normal encouragement of early-childhood creative-performance instincts (we see several glimpses of this, including his attempt to read horrifying medieval cautionary tales to the kids during bring-your-child-to-work day, and his own description of his childhood, which left his brother actually developmentally disabled). He has therefore developed none of the addiction to childhood applause-seeking performance behaviors that have trapped Michael. Instead, Dwight found relief in the graded, performance-oriented worlds of school and varied medieval-guild-like worlds, such as farming, animal husbandry and karate. His attempts to understand the world of management, which is decidedly not a world of grades or guilds, are based entirely on peripheral guild-like elements. He is the only one excited about the Survivor-style successor-selection event Michael arranges (in the bus on the way over, he asks, “Will there be business parables?”). When he attempts manipulation, his mind naturally turns to hidden microphones, doctored documents and other elements of tradecraft learned from spy novels, and only rarely to psychology. He banks the occasional tactical victory, but cannot play or win the mind games required to beat the Sociopaths. In Dwight’s world, everything worth learning is teachable, and medals, certificates and formal membership in meritocratic institutions is evidence of success. Even where play behaviors are concerned, the Dwights of the world can more easily get lost in points-and-rules worlds. It is significant that Dwight has never seen/read Charlie and the Chocolate Factory (which is about creative-performance play), but is obsessed with gaming worlds and sci-fi/fantasy universes. Perhaps the clearest example of Dwight’s need for formal affiliation is his lame attempt at the insider stand-up comedy routine, The Aristocrats. To Dwight, everything is a formal contest, and there are always authority figures who provide legitimacy and rankings. He has no sense of humor (thanks to skipping early childhood), and has no idea how to actually evoke laughter, so he tries to ace the only formal membership test he can see, the ability to tell the Aristocrats joke. Michael, by contrast, can at least tell juvenile jokes, and Andy can manage some bad frat-boy humor. Rao argues that Michael Scott, the “boss” in the show, is stuck at an even lower level: Little children in normal environments win their first victories through creative performance: reciting nursery rhymes, drawing pictures, and demonstrating creative play behaviors. If they succeed too much, they get addicted to the typical adult reaction: Wow, aren’t you cute/clever? and, to a lesser extent, to admiration from younger siblings. In learning to thrive in this particular reward/penalty environment, little children rely mostly on responding to the emotional content of what they hear and see, since they do not understand much. With a few evolved defense mechanisms thrown in, to protect against adult realities that don’t conform to childhood environments, that’s exactly what it feels like to be Michael. When he hears somebody talking, all he hears is “blah blah blah good job, blah blah blah, how could you do this Michael?” in conjunction with facial expressions and body language. Michael’s head is a massive library of childlike mappings between situations, canned phrases and reactions. He is not completely responsible for his actions and utterances because he genuinely does not understand them. There is coherence in what Michael says though; he does not sound completely nonsensical because he reacts meaningfully to body language, facial expressions and emotional cues. “You talkin’ to me?” (borrowed from De Niro) is a belligerent line, and by pulling out that line when he feels threatened, and then displacing the tension with laughter, Michael is able to derail the conversation. His trademark joke, “That’s what she said!” is an extreme example. It makes no sense in most contexts where he trots it out; its only purpose is to dissolve tension and displace threats. Either laughing with Michael or throwing up your hands in frustration is a victory for him. The only effective response is to calmly ignore his disruptive actions, wait for the reaction to die down, and continue the conversation in dominant mode, like Cesar Milan with his dogs … Around Packer, his boorish friend, insulting and objectifying ways of talking about women gain approval, so he trots out borrowed, misogynistic man-talk. Withering under the collective glare of his politically correct employees, phrases like “respect women” gain smiles and halt frowns, so that’s what he offers. […] Here is why: delusions are closed logical schemes, where reality is mangled into the service of a fixed script through defense mechanisms, with the rest of the meaning thrown away. To manufacture original thought you have to look at/listen to reality in open ways for data. That is why Michael’s database is so full of movie lines. Movies are goldmines of canned situation-reactions that don’t require much present-reality data to retrieve. When kids quote adults or movies, they seem precocious, and gain approval. In an era where more kids are raised by TV than by parents, parroting movie lines comes more naturally than repeating bromides learned from parental figures or at churches and temples. Recall that social calendars force you through later stages whether or not you master previous ones. So what about later stages? Michael is not quite as enamored of medals and certificates as Dwight because (as a lousy student) he never got very good at earning them, and could therefore not get seriously addicted to them. Finally, Michael has poorly developed peer-affiliation drives. He wants to be the center of attention, not one among many equals in a huddle of peers. When Michael appears to be operating under a peer-affiliation drive (the sort that animates Andy), he is really casting child behaviors into a teen mould. He believes that specific people, rather than formal or informal groups, are cool or admirable (proxy parental figures, older siblings). If they are not cool or admirable, they must be made to view him as cool and admirable (younger siblings). I was struck by a line in an appendix, saying this is the same level that Nazi bureaucrats were at. Just for fun, let’s compare the rest of Rao’s profile of Michael with Arendt’s profile of Adolf Eichmann (all quotes taken from my Eichmann In Jerusalem review): Despite all the efforts of the prosecution, everybody could see that this man was not a “monster,” but it was difficult indeed not to suspect that he was a clown. And since this suspicion would have been fatal to the whole enterprise, and was also rather hard to sustain, in view of the sufferings he and his like had caused so many millions of people, his worst clowneries were hardly noticed. What could you do with a man who first declared, with great emphasis, that the one thing he had learned in an ill-spent life was that one should never take an oath (“Today no man, no judge could ever persuade me to make a sworn statement. I refuse it; I refuse it for moral reasons. Since my experience tells me that if one is loyal to his oath, one day he has to take the consequences, I have made up my mind once and for all that no judge in the world or other authority will ever be capable of making me swear an oath, to give sworn testimony. I won’t do it voluntarily and no one will be able to force me”), and then, after being told explicitly that if he wished to testify in his own defense he might “do so under oath or without an oath,” declared without further ado that he would prefer to testify under oath? And: The judges were right when they finally told the accused that all he had said was “empty talk” – except that they thought the emptiness was feigned, and that the accused wished to cover up other thoughts which, though hideous, were not empty. This supposition seems refuted by the striking consistency with which Eichmann, despite his rather bad memory, repeated word for word the same stock phrases and self-invented clichés (when he did succeed in constructing a sentence of his own, he repeated it until it became a cliché) each time he referred to an incident or event of importance to him. Whether writing his memoirs in Argentina or in Jerusalem, whether speaking to the police examiner or to the court, what he said was always the same, expressed in the same words. The longer one listened to him, the more obvious it became that his inability to speak was closely connected with an inability to think, namely, to think from the standpoint of somebody else. No communication was possible with him, not because he lied but because he was surrounded by the most reliable of all safeguards against the words and the presence of others, and hence against reality as such. And finally (this time in my voice): If [Arendt] has any thesis at all, it’s that Eichmann believed in something larger than himself. We usually encourage this sort of thing, but I think the prosocial version involves having a specific larger-than-yourself thing in mind. Eichmann (says Arendt) just liked larger-than-himself things in general, and the Nazi vision of eternal struggle for racial supremacy was the biggest thing he could find in the vicinity. We’ll later see that he had a strange respect for Zionists, and this was because they too believed in something larger than themselves. Eichmann’s infamous cliches were the cliches of pomp and circumstance and glory and high words, the ones which made him feel like he was engaged in a great enterprise whether or not there was anything behind them. The reason he admitted neither to “just following orders”, nor to a deep personal belief in anti-Semitism, was that his loyalty to Hitler came from neither. When Hitler said to kill all the Jews, he gladly complied; if Hitler had said to kill all the Christians, he would have done that too. Not because he was a drone following orders to save his skin, but because he believed. Not in any of the specifics of Nazi ideology. Not even in Hitler’s personal judgment. Just in whatever was going on at the time. IV. When he gets to the next section, on Losers, Rao mostly forgets the developmental psych. Now this is a book on status economics. Rao’s poetic description: Each of them – and they constitute 80% of humanity – is born the most beautiful baby in the world. Each is an above-average child; in fact the entire 80% is in the top 20% of human beings (it’s crowded up there). Each grows up knowing that he or she is deeply special in some way, and destined for a unique life that he or she is “meant” to live. In their troubled twenties, each seeks the one true love that they know is out there, waiting for them, and their real calling in life. Each time they fail at life or love, their friends console them: “You are a smart, funny, beautiful and incredibly talented person, and the love of your life and your true calling are out there somewhere. I just know that.” The friends are right of course: each marries the most beautiful man/woman in the world, discovers his/her calling, and becomes the proud parent of the most beautiful baby in the world. Eventually, each of them retires, earns a gold watch, and somebody makes a speech declaring him or her to be a Wonderful Human Being. You and I know them as Losers. Being a Loser means clinging to the delusion of being special, while also being fully accepted by your social group (indeed, your specialness only matters instrumentally and insofar as other people appreciate you for it). But these two imperatives are Scylla and Charybdis: insist too hard on actually being special and you’re a narcissist who everyone hates; try too cravenly to seek acceptance, and you’re acknowledging other people are better than you. Rao views Loserdom as a series of conspiracies to manage this paradox. The end solution looks something like "everyone is special in their own way”. Loser dynamics are largely driven by Lake-Wobegon-effect snow jobs, which obscure pervasive mediocrity. But unlike the delusions of the Clueless (false confidence of the Dunning-Kruger variety which we saw last time), which are maintained through the furious efforts and desperate denials on the part of the deluded individuals themselves, Loser delusions are maintained by groups. You scratch my delusion, I’ll scratch yours. I’ll call you a thoughtful critic if you agree to call me a fascinating blogger. And we’ll both convince ourselves that our lives are to be valued by these different measures. Loser above-averageness is generally not based on an outright falsehood. Unlike Michael’s pretensions to comic genius, which are strictly not true, Pam really is the best artist in the group. The delusion lies not in a false assessment of her artistic skills, but in the group choosing to evaluate her on the basis of art in the first place. In other words, Losers are too smart to fool themselves. They enter into social contracts which require them to fool each other […] At the life-script level, the game-playing social contract creates complete nominal illegibility. Each individual in a group is judged according to a custom life script that makes it impossible to compare two lives within the group. Pam’s life has a redemptive script based on the fact that she is the cutest one in the office, can paint well, and forms the “It” couple with Jim. Kevin’s is based on the fact that he is in a band. Creed’s uniqueness lies in his weirdness…Remember, you are unique, just like everybody else. A second, corollary paradox: Groucho Marx joked that he wouldn’t belong to any club that would accept him as a member. But then why do people ever associate in clubs? Suppose you joined a club that was clearly not good enough for you - maybe you’re a famous billionaire and they’re a bunch of losers who watch crappy TV in a basement once a week. Why would you be in this club? But suppose you tried to join a club that was clearly too good for you - you’re a poor person with no social skills, and you apply to the rich billionaires’ country club. Why would they ever accept you? This suggests that people won’t join clubs that are too much higher or lower status than they are. But why would they join clubs that are even slightly higher or lower status? Wouldn’t you expect nobody ever joins anything except in the vanishingly rare case where their status and the club’s status are exactly the same? Rao is trying to make the point that all associations require some level of status illegibility. If you knew status perfectly - if you went around with “Status: 6.8/10” tattooed on your forehead - then you could see a club all of whose members had statuses 6.2 - 6.5, and know that you could do better. So instead, the same social conspiracy that keeps people convinced they have useful talents, also keeps status illegible. This takes the form of everyone teasing each other, creating a constant churn of minor status increases and decrements which is too complicated for anyone to track properly. (Rao says that the single-highest and single-lowest status people in any group can sometimes be legible - creating an observable range for what status people in the group can be, ie “we’re for people between 6/10 and 7/10” - but the middle always has to be illegible, to allow the majority of people to preserve their polite fiction that they’re among the higher-status members of their group.) This section on status economics ends with a digression on jokes. Not as in knock-knock jokes. Jokes where one person makes fun of another, gaining status at their expense. These kinds of jokes are status economics transactions. According to Rao, the minimum viable Loser joke is three people: the joker, the victim, and an audience. The joker makes a joke. The victim has a chance to retort (eg “takes one to know one!”) and the audience decides how to mentally update everyone’s status. Rao uses examples from The Office, but I haven’t seen it, so I was thinking about an episode of Seinfeld: When George was stuffing himself with shrimp at a meeting, Reilly remarked, "Hey, George, the ocean called. They're running out of shrimp." Slow-witted George could not think of a comeback until later, while driving to the tennis club to meet Jerry. His comeback was: "Oh, yeah, Reilly? Well, the jerk store called, and they're running out of you." Jerry, Elaine, and Kramer did not think 'jerk store' was a good comeback mainly because "there are no jerk stores." Elaine suggests, "Your cranium called. It's got some space to rent." Jerry suggests, "The zoo called. You're due back by six." Kramer finally thinks George should just tell Reilly that he slept with his wife. After discovering that Reilly was let go from the Yankees and now works for Firestone, George flies to Akron, Ohio just to try the jerkstore line. When he says it, however, Reilly responds, "What's the difference? You're their all-time best seller." George, unprepared for this, ends up using Kramer's line. He's then told that Reilly's wife is in a coma. Rao asks: in what sense did Reilly successfully “score” on George? Suppose George had been a very stupid person, and hadn’t understood that Reilly’s comment was supposed to be teasing/hurtful; he would have been unaffected. Or suppose he had something totally outlandish (“Yes, but there are canyons on Mars”), then insisted that it was a brilliant comeback and let Reilly exhaust/embarrass himself trying to prove it wasn’t? In contrast, if there had been a third person there (let’s say a love interest who both George and Reilly were pursuing), this pointless narcissistic zero-stakes game would become relevant: the love interest gets to evaluate the two against each other, and award status to the victor. This isn’t always the wittier of the two. You can also imagine a world where George says “Excuse me, I have an eating disorder, I think it’s incredibly stigmatizing for you to bully me like this.” Then the third person gets to decide whether to treat this as Reilly making a hilarious joke and George being too thin-skinned to take it, or as Reilly saying something offensive and George bravely calling him out. Crucially, if she wants, she can let her decision hinge on whether she liked Reilly or George better to begin with, or whether one or the other would be a better ally in the future - so this is part status-transaction and part status-test. But in the actual Seinfield episode, there is no love interest. George and Reilly are trying to score points on each other, totally unaware that this is meaningless. For Rao, this is a sure sign of Cluelessness - anyone with social skills would realize no status could be gained or lost and the whole game is pointless. So Loser jokes are 3+ people, and Clueless jokes are 2 people. Continuing the pattern, a Sociopath joke must be for one person - the joker amusing himself, totally unconcerned whether anyone else appreciates it. V. Sociopaths aren’t necessarily evil. They’re just . . . unbeholden to anyone else. They might still follow the rules because it advantages them to do it, or because they have personally chosen to follow some moral code they happen to like. But they don’t crave approval from anyone, not even abstract concepts. If the Clueless come from arrested development, and Losers from normal development and its attendant status economics, Sociopaths are formed by a sort of dark enlightenment. They have a moment when they realize nothing is true and everything is permissible. Rao’s poetic side writes: Sociopathy is not about ripping off a specific mask from the face of social reality. It is about recognizing that there are no social realities. There are only masks. Social realities exist as a hierarchy of increasingly sophisticated and specialized fictions for those predisposed to believe that there is something special about the human condition, which sets our realities apart from the rest of the universe. There is, to the Sociopath, only one reality governing everything from quarks to galaxies. Humans have no special place within it. Any idea predicated on the special status of the human — such as justice, fairness, equality, talent — is raw material for a theater of mediated realities that can be created via subtraction of conflicting evidence, polishing and masking. Mask is an appropriate term for any social reality created through subtraction, because an appearance of human-like agency for non-human realities is what the inhabitants require. By humanizing the non-human universe, we make the human special. All that is required is to control people who believe in fairness, is to remove any evidence suggesting that the world might fundamentally not be a fair place, and mask it appropriately with a justice principle such as an afterlife calculus, or a retirement fantasy. […] When a layer of social reality is penetrated and turned into a means for manipulating the realities of others, it is automatically devalued. To create medals and ranking schemes for the benefit of the Clueless is to see them as mere baubles yourself. To turn status-seeking into a control mechanism is to devalue status. To devalue something is to judge any meaning it carries as inconsequential. In terms of our metaphor of masks of gods, the moment you rip off a mask and wear it yourself, whatever that mask represents becomes worth much less. So the Sociopath’s journey is fundamentally a nihilistic one. The climactic moment in this journey is the point where skill at manipulating social realities becomes unconscious. Suddenly, it becomes apparent that all social realities are based on fictional meanings created by denying some aspect of natural, undivided reality. Reality that does not revolve around the needs of humans. The mask-ripping process itself becomes revealed as an act within the last theater of social reality, the one within which at least manipulating social realities seems to be a meaningful process in some meta-sense. Game design with good and evil behaviors. Losing this illusion is a total-perspective-vortex moment for the Sociopath: he comes face-to-face with the oldest and most fearsome god of all: the absent God. In that moment, the Sociopath viscerally experiences the vast inner emptiness that results from the sudden dissolution of all social realities. There’s just a pile of masks with no face beneath. Just quarks and stuff. Both Losers and Clueless are trying to manipulate other people’s impressions of them. Sociopaths are trying to manipulate reality. Reality includes other people’s impressions - if your goal is to become President, in some sense you care what the electorate thinks of you. But it’s an instrumental goal. Sociopaths crave the Presidency (or whatever) and use other people’s good opinions as stepping-stones. Losers and Clueless crave the good opinions directly. Once you stop craving other people’s good opinions, you lose some mental blocks that would normally prevent you from coming up with manipulative strategies. Rao says the most basic Sociopath manuever is “heads I win, tails you lose” - coming up with some way of arranging systems so that they get the credit for good results while avoiding the blame for bad ones. A simple strategy is to come up with a plan and appoint a Clueless pawn as Director Of The Plan. If the plan goes well, it was always your idea and you hand-picked and mentored the person who carried it out. If the plan goes poorly, it was always the director’s idea, you maybe thought it had some promise but he clearly bungled the execution. But this is a weak 101-level version of the maneuver; the real thing involves a bunch of bureaucracies, committees, and total deniability. Rao theorizes that most of the middle layers of companies are giant and powerful machines built by Sociopaths to guide and redirect the flow of blame and credit. Is everyone else against this? Do they view it as duplicity and oppression? Rao says no. Sociopaths aren’t just CEOs. They’re priest-kings, creating meaning for everyone else. The Clueless demand a world of legible rules, legible rewards and punishment, and a legible Authority tracking everyone’s balance. Sociopaths, who create companies, religions, governments, and every other form of authority, help Clueless people live in the legible gamified rank-able worlds their minds crave. I’m less able to follow Rao’s explanation of “Loser spirituality” and how Sociopaths control it. My guess is something like: Losers “worship” positive emotions, belongingness, and “good vibes”, within carefully obfuscated conspiracies of mutual status-blindness. These aren’t really capable of dealing with the real world: a typical fiction is that “we’re all really talented and gave our all on this project”, but in fact the project might be failing. Sociopaths are outside those conspiracies and outside local status competitions, ie your CEO isn’t going to share banter over a glass of beer with you. So they are allowed to (carefully, emotionlessly) communicate/represent/convey reality to the status-maintenance conspiracies in a way where no particular member loses status by admitting reality first. Although in some vague sense the Sociopaths are oppressing and manipulating everyone else, this isn’t how it feels from the inside: both Clueless and Losers are grateful to the Sociopaths for taking the burden of confronting reality off their shoulders. If the Sociopath fails at this, and a Clueless or Loser has to confront reality unmediated, they’ll either have a very bad time but eventually bounce back, or become a Sociopath themselves. VI. So that’s The Gervais Principle. Is any of it true? I don’t find myself or the people I know best falling clearly into any of these archetypes. They’re useful to have around. I can see pieces of all of them. But none are a great match. I can see bits of myself in the Clueless archetype. I like legible systems. I’m the person who did really well on standardized tests, really badly at networking, and ended up in medical school because it was the highest you could go on test scores alone. I’ve occasionally suggested that all politics should be replaced with some kind of system for calculating how much utility every option has, then doing whichever one is best (bonus points if it’s on the blockchain). But I’m bad at listening to authority figures,and quit my last job to start my own company. Also, Clueless people are supposed to be bad at using language in original ways, and I’m a professional writer. Sociopaths are supposed to fiercely distrust collectivism and come up with their own, usually utilitarian-inspired morality, which I identify with. But I can’t manipulate my way out of a paper bag. Also, a few weeks ago I got in an argument with a clerk over the right amount of change, after double-checking it turned out I was wrong and the clerk was right, and even though this was in an airport and I will definitely never see that clerk again, I felt embarrassed about the interaction for hours, and still feel pretty bad about it. Doesn’t really feel very ubermensch-ish or transcended-the-need-for-other-people’s-good-opinion-y. I have a group of friends, and within that group of friends I’m acutely aware of the things I’m unusually good at vs. bad at, and I worry a lot about whether my strengths qualify me to be a member in good standing. My status within that group is illegible and I prefer that to the alternative. Does that make me a Loser? Who controls the microphone in my head? Whose approval do I crave? When I was younger, I remember pretty vividly that it would be whoever I had a crush on at the time. When I started blogging, it became my blog audience. But sometimes it gets hijacked by random store clerks. And I particularly remember being invited to an event with some big name tech people, fretting about whether they would like me, exerting some willpower to remind myself that I was valid with or without their approval, and then realizing afterwards that what I had actually done was fantasize about how if I wasn’t obviously craving their approval, they would be impressed by my independence and put-togetherness and respect me even more. So fine, I (and the few other people I know well enough to use as examples) don’t naturally fall into any of these categories. Whatever, Rao said (in one sentence) that everyone has multiple types. But then what’s the use of this categorization system? If I invent three random types of people: Green: introverted, long hair, likes the cold, complains too much
Fitbit

Fitbit is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 14, 2021 and May 14, 2021. The archive places it in contexts such as "We would all chase after more steps with our Fitbits". It most often appears alongside Addiction by Design: Machine Gambling in Las Vegas, Amazon, American Gaming Association.

Reference entry
Fitbit
Mention count
1
Issue count
1
First seen
May 14, 2021
Last seen
May 14, 2021
May 14, 2021 · Original source
You might remember the gamification craze from the beginning of this decade. App creators were convinced that adding badges, randomness, and leveling up to any activity would make it irresistible. We were promised a new world where the power of gaming would be used for good. We would all chase after more steps with our Fitbits, more languages with Duolingo, and more math with Khan Academy. Move aside Portal and poker, there were new sheriffs in town.
And yet, despite following a lot of the same strategies that gambling machine designers did, those app creators never did create an army of self-improvement addicts. I haven’t heard any tales of someone losing his job because he was too busy getting more steps with his Fitbit, neglecting her marriage because she was too busy learning a new language on Duolingo, or dropping out of school to make more time for Khan Academy. Why is that? If designers can turn creaky slot machines into a multibillion dollar addictive product, why couldn’t they do the same for all these virtuous apps? Why can I, a person who gets addicted to apps fairly easily, not bring myself to spend more than ten minutes on Duolingo? Why are these apps still more broccoli than chocolate?
Flavor Aid

Flavor Aid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2022 and June 23, 2022. The archive places it in contexts such as "907 inhabitants of Jonestown drank Flavor Aid laced with cyanide". It most often appears alongside 1978, 2016 essay, A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs.

Reference entry
Flavor Aid
Mention count
1
Issue count
1
First seen
June 23, 2022
Last seen
June 23, 2022
June 23, 2022 · Original source
For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
Fliff

Fliff is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 13, 2024 and May 13, 2024. The archive places it in contexts such as "this loophole, but it’s already used by sites like Chumba Casino and Fliff". It most often appears alongside 17 CFR Part 40, 2024 election, Austin.

Reference entry
Fliff
Mention count
1
Issue count
1
First seen
May 13, 2024
Last seen
May 13, 2024
  • 24 May 13, 2024
May 13, 2024 · Original source
In the interests of continuing to exist and push prediction markets forward, they will switch to a “sweepstakes” model. Although gambling is illegal in most US states and requires complicated licensing in others, there’s a “sweepstakes loophole”; companies are allowed to offer “prize sweepstakes”, and you can use this to sort of reconstruct the concept of gambling in a legal way. You don’t give the company money and get back money. You pay for “points”, get “sweepstakes tokens” as a bonus, gamble the “sweepstakes tokens”, and then cash in the sweepstakes tokens for money. This is a pretty surprising loophole, but it’s already used by sites like Chumba Casino and Fliff. (and apparently it creates weird incentives! In order to maintain the fiction of being a “sweepstakes”, these casinos have to give you “tokens” if you request them by mail. If you send a postcard to Chumba Casino asking for free money, they’ll give it to you, $5 per postcard. Is this an infinite free money pump? My impression is in theory yes, but the postcards have to be handwritten in a very specific way, the company sometimes rejects them for weird reasons, the cost of materials and mailing lowers your profit to more like $4, and so you’d have to hand-write 250 postcards to make $1,000. I’m still surprised more people don’t do this.) Because real money is involved, Manifold will have to tighten the rules on markets, including banning N/A resolutions. You can see a full list of changes here. Manifold users are split between acknowledging that the for-profit company they love needs some way to make money, being salty about the changes, and being worried that creating more of a casino atmosphere will be bad for users / the world / ability to function as a good prediction market. (I understand most of the NO vote here is based on the theory that there will be legal intervention - maybe because the government is willing to tolerate sweepstakes casinos but not sweepstakes prediction markets). Manifold co-founder Austin Chen won’t be involved. He’s leaving the site - not explicitly because of the pivot, he just said it seems to be “trapped in local optima”. He plans to focus on other parts of the Manifold empire, especially Manifund, which tests impact markets, regranting, and other “experimental” charity models. Manifold will continue in the hands of the other two co-founders, James and Stephen Grugett. Superhindcasting I mentioned this in my lab leak post, but it deserves more attention here: Good Judgment Project’s report on Superforecasting The Origins Of The COVID-19 Pandemic. Good Judgment Project employs superforecasters who will predict things for clients. Some people interested in COVID origins asked them to judge whether lab leak was plausible. Their headline result was 74% zoonosis, 25% lab leak, 1% something else. Part of GJP’s method is getting their forecasters to share sources and talk to each other. Here’s the graph for how that went: People changed their minds a little over time, but not in a very consistent way that mattered much in the end. What was the “client feedback”? The report says: Client feedback was provided to the Superforecasters on December 21. The client posed questions to the Superforecasters about their assessments up to that date and asked for their reactions to several studies and articles. In the days following the client engagement, the Superforecasters lowered their confidence in the natural zoonosis hypothesis from 73% to 67%, although zoonosis remained the most likely potential cause in their assessment. But following an active engagement with recent genomic studies and historical base rates of zoonotic spillovers, those numbers began to return to earlier levels. January also saw increased attention to the geopolitical context and transparency issues, particularly related to research activities in Wuhan Is this bad? I’m imagining a pro-lab-leak client saying “But what about [this list of pro-lab-leak arguments]?” and then the superforecasters read them and adjust. In one sense, it’s good that they got to see more arguments; on the other, it seems like a potential route by which clients could bias the results - probabilities never quite got back to where they were before the feedback, though they got pretty close. The last-minute spike for zoonosis might be the Rootclaim debate results, which were released on 2/18. So maybe the client feedback and the Rootclaim results both slightly affected the numbers, but mostly the superforecasters started out pro-zoonosis and stuck to their guns. Dan Schwarz and the FutureSearch team say that forecasting has a “rationale-shaped hole”. Despite the report making this sound like a pretty intense process, we don’t get much information about details: In their extensive discussions , Good Judgment’s Superforecasters assessed base rates and historical patterns, existing evidence and scientific analysis, geopolitical context and transparency concerns, trust in intelligence communities, and methodological constraints. 1. Base Rates and Historical Patterns: The Superforecasters frequently referenced base rates, i.e., the history of pandemics emerging from natural zoonosis versus the history of laboratory leaks, to anchor their probabilities. For the former, they discussed how the base rates are changing as the climate warms and as expanding human populations push farther into natural environments that previously saw little human presence. For the latter, they acknowledged that it has only been 12 years since the advent of CRISPR gene- editing tools, and the base rate of lab leaks in the short synthetic biology era is not yet well established. 2. New Evidence and Scientific Analysis: Throughout the period, the Superforecasters adapted their forecasts in light of new scientific evidence, including genomic analyses of SARS-CoV-2 and its relation to bat viruses, and the debate over potential laboratory manipulation. 3. Geopolitical Context and Transparency Concerns: The geopolitical implications of the virus’s origins, particularly in relation to China’s transparency and the involvement of international research institutions, played a significant role in the analysis. Concerns over data veracity, and over the political ramifications of determining that the pandemic’s origins were other than zoonosis, were extensively debated. 4. Trust in Intelligence: Commentary on trust in intelligence communities and discussions about the impact of geopolitical biases on the interpretation of evidence illustrated the complex interplay between science, politics, and human behavior in assessing the pandemic’s origins. 5. Methodological Critiques and the Evaluation of Evidence: The Superforecasters engaged in methodological critiques of the evidence base, including the scrutiny of laboratory practices and biocontainment levels [...] In the end, most Superforecasters were in rough agreement on issues like the base rates of zoonotic spillover. Where they most often disagreed was on the interpretation of actions by Chinese officials and whether their actions reflected how an authoritarian government would react in any crisis over which it did not have full control, or whether those actions were indicative of attempts to cover up a biomedical research-related accident that allowed the SARS-CoV-2 virus to enter circulation in China and, ultimately, the entire globe. Probably it would be too much to ask for to get a transcript of all their discussions - then they’d be nervous saying things that might make them look bad to an audience. What would be a good balance between getting more information and not imposing on their time? Forecasting is an unusually legible and easy-to-judge domain. One of the theories of change for forecasting was to use it to identify smart people with good reasoning, then turn them loose on less well-behaved problems. This is one of the first big attempts to do this at scale. How did it work? We can’t tell, because it’s inherently an illegible and hard-to-judge domain. Darn. I don’t know what I expected. Notes From A Local Optimum Austin’s concern - that forecasting has reached a local optimum - is widely shared. We have some good sites: Manifold, Metaculus, Polymarket, GJO, etc - all doing good work. We have good-ish probabilities for a few important questions. Every so often a news source cites them. Sometimes a decision-maker looks at them behind the scenes, maybe. Is this all there is? The FutureSearch team says the next step is to focus on “rationale”. We need to use forecasting not just to get a raw probability, but to explain what’s going on and why we think something. Then instead of just convincing policy-makers to trust forecasts, we can tell them why something is true, or inform their discussions even if they’re not willing to blindly trust a number. Is this a betrayal of the forecasting ethos? The original dream was that instead of a bunch of people giving arguments, we could just test who was right. Now we’re going back to the arguments? People have argued forever; what does forecasting add to that? Well, they add the knowledge that the arguments are from people who have been right a lot before and are incentivized to be right again. Still, it’s not a natural fit. Probably it’s relevant here that FutureSearch’s forecasting AI does a really good job of this by default, in a way humans can’t match. Nuno’s yearly forecasting roundup doesn’t have a single thesis, but the first part is a well-supported complaint that most forecasting sites aren’t good business. They either burn VC money, burn EA donations, or converge towards casinos to support themselves. He gives an honorable exception to Cultivate Labs, which sells prediction market software rather than the results themselves. Open Philanthropy (billionaire Dustin Moskovitz’s EA-aligned charitable foundation) has at least given forecasting a vote of confidence, recently choosing to promote it to one of their main donation areas. Still, they got a lot of pushback on the decision, for example SuperDuperForecasting here: This will be a total waste of time and money unless OpenPhil actually pushes the people it funds towards achieving real-world impact. The typical pattern in the past has been to launch yet another forecasting tournament to try to find better forecasts and forecasters. No one cares, we already know how to do this since at least 2012! The unsolved problem is translating the research into real-world impact. Does the Forecasting Research Institute have any actual commercial paying clients? What is Metaculus's revenue from actual clients rather than grants? Who are they working with and where is the evidence that they are helping high-stakes decision makers improve their thought processes? Incidentally, I note that forecasting is not actually successful even within EA at changing anything: superforecasters are generally far more relaxed about Xrisk than the median EA, but has this made any kind of difference to how EA spends its money? It seems very unlikely. And Marcus Abramovich here: I'm in the process of writing up my thoughts on forecasting in general and particularly EA's reverence for forecasting but I feel, similar to @Grayden that forecasting is a game that is nearly perfectly designed to distract EAs from useful things. It's a combination of winning, being right when others are wrong and seemingly useful, all wrapped into a fun game. I'd like to see tangible benefits to more broad funding of forecasting that seems to be done in t he millions and tens of millions of dollars. I would also be the type of person you would think would be a greater fan of forecasting. I'm the number one forecaster on Manifold and I've made tens of thousands of dollars on Polymarket. But I think we should start to think of forecasting as more of a game that EAs like to play, something like Magic the Gathering that is fun and has some relations to useful things but isn't really useful by itself. Eli Lifland has a long and hard-to-summarize comment here, response from Ozzie Gooen here, podcast between them on “Is Forecasting A Promising EA Cause Area?” here. I’m split on this. My previous hope was that the field would gradually grow, without any qualitative changes or discontinuities, until it became big enough that journalists and policy-makers were aware of it and took it seriously (compare eg the growth of the Internet as a scholarly resource). I think the strongest argument against this is Manifold’s relatively flat user numbers. Is there a new hope? I think if nothing else, forecasting might be useful as a testing ground: First, to create forecasting AIs (like FutureSearch) which can then get consulted on a variety of questions, eg by policy-makers. The biggest holdup has always been the need to gather 20 or 50 or however many hard-to-find superforecasters for whatever question you’re asking, and then trust their advice even though they’re fallible fleshbag humans. If you can use the 20 to 50 superforecasters to inspire an AI, and then test the AI and prove it’s good, people might be more interested. This is especially true if the AI can branch out beyond traditional forecasting questions. Once we have a few of these, we can start comparing the next generation of AIs to the previous generation, and skip the superforecasters.
Ford F-150

Ford F-150 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "It’s only recently that the Ford F-150 has arrived as mostly aluminum". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Ford F-150
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Musk’s word choice there—“obvious decision”—goes a long way toward explaining how he operates. Yes, the car needed to be light, and, yes, aluminum would be an option for making that happen. But at the time, car manufacturers in North America had almost no experience producing aluminum body panels. Aluminum tends to tear when worked by large presses. It also develops lines that look like stretch marks on skin and make it difficult to lay down smooth coats of paint. “In Europe, you had some Jaguars and one Audi that were made of aluminum, but it was less than five percent of the market,” Musk said. “In North America, there was nothing. It’s only recently that the Ford F-150 has arrived as mostly aluminum. Before that, we were the only one.”
Formula 281

Formula 281 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 02, 2021 and March 02, 2021. The archive places it in contexts such as "made a popular over-the-counter diet pill called Formula 281". It most often appears alongside 1938 FDA, 2,4-dinitrophenol, 2,4-dinitrophenol.

Reference entry
Formula 281
Mention count
1
Issue count
1
First seen
March 02, 2021
Last seen
March 02, 2021
March 02, 2021 · Original source
In the 1930s, a shady outfit called Isabella Laboratories made a popular over-the-counter diet pill called Formula 281 (slogan: "281 for the too weighty one"). If you're familiar with any of: the 1930s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?". Actually, no! It contained 2,4-dinitrophenol, a mitochondrial uncoupling agent.
Foster Farms

Foster Farms is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "undercover investigation of poultry-giant Foster Farms". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
Foster Farms
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Legal Impact for Chickens (LIC) is so grateful to ACX for launching us, and to all the ACX readers who have supported us! Thus far, LIC has filed four lawsuits: (1) Smith v. Vachris, the shareholder derivative case against Costco’s executives for chicken neglect, which was mentioned in The Washington Post, Fox Business, CNN Business, Meatingplace, and a viral TikTok. (2) LIC v. Case Farms, a cruelty suit against a major KFC supplier, which is currently pending before the North Carolina Court of Appeals. (3) Animal Outlook v. Harvey’s Market, which successfully stopped a DC butcher shop from selling foie gras. And (4) LIC v. Alexandre, a cruelty suit against an abusive dairy, which is currently pending before a California court. LIC has also sponsored an undercover investigation of poultry-giant Foster Farms, leading to a currently ongoing sheriff’s-office investigation. LIC got a California caterer to drop foie gras with a simple cease-and-desist letter. And LIC established a new potential avenue to create consequences for animal abuse: through an amicus brief at sentencing for the violation of another law. LIC also received a recommendation from Animal Charity Evaluators!
Free Universal Construction Kit

Free Universal Construction Kit is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "The unfortunately-acronymed Free Universal Construction Kit is “a collection of open source 3D-printable adapters". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
41: The unfortunately-acronymed Free Universal Construction Kit is “a collection of open source 3D-printable adapters that [enables] interoperability between ten popular children's construction toys”, ie connect Legos, Tinkertoys, Lincoln Logs, etc.
French’s

French’s is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2025 and August 08, 2025. The archive places it in contexts such as "French’s (now best known for mustard) tried to introduce “instant mashed potatoes”". It most often appears alongside Ainu, Altiplano, American cheese.

Reference entry
French’s
Mention count
1
Issue count
1
First seen
August 08, 2025
Last seen
August 08, 2025
August 08, 2025 · Original source
These shreds resemble the ancestral stock of modern Instant Mashed Potatoes (source) The result was an affront. The potatoes were swimming in their own gluten, released during the granule-making process, which when mixed with imprecise water ratios made for a slop that was somehow both gluey and soupy. Immediately after the war, French’s (now best known for mustard) tried to introduce “instant mashed potatoes” as a consumer product category. America’s veterans were not having it. They didn’t want to be reminded of the awful slurry they’d had on the front. The commercial fortunes of instant mashed potatoes began to turn around a decade later, however, when food scientists in the US and Canada converged on methods for producing dehydrated potato flakes rather than granules. The flakes had substantial advantages. They didn’t get as glutinous when reconstituted. Their geometry made them easier to dry quickly, on the order of minutes or even seconds. Using a multi-step process called the “Philadelphia Cook”, they could lock in a more natural flavor. When prepared on the stove with butter and milk, they were supposed to turn out almost as good as the real thing without any onerous prep work on the part of the consumer. This raises the question, though, of why food scientists kept working on improving instant mashed potatoes a decade after they were no longer required for the war effort. If you’re no longer constrained by having to stick it to the Axis, why not return to Glasse-style maſhed potatoes in all circumstances? This is a pattern that recurs frequently in reading about American foodways of the 20th century: choices and innovations made under extreme duress in the World War II economy didn’t fade away when the duress subsided. Instead they echoed back into American life a few years later, despite the lean conditions that birthed them being replaced by extreme abundance. Why did America start eating like it was on a total war footing again when my parents’ generation was young? There are a lot of overlapping explanations. Here are a few: Industrial inertia: Companies that had spun up to supply a vast army didn’t want to shut down overnight, so they necessarily pivoted to the consumer market. Some of these efforts succeeded at entrenching new consumer categories (fish sticks, canned peaches) while others (hamburgers-in-a-can) did not.
fried chicken

fried chicken is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 19, 2026 and March 19, 2026. The archive places it in contexts such as "“I’ll have, uh, the fried chicken, and a Coca-Cola,” he said". It most often appears alongside Baltimore, calea zacatechichi, Causal Ocean.

Reference entry
fried chicken
Mention count
1
Issue count
1
First seen
March 19, 2026
Last seen
March 19, 2026
March 19, 2026 · Original source
“I’ll have, uh, the fried chicken, and a Coca-Cola,” he said. The waitress beamed at him. “Great choice. And your guest says he’ll be just a little late.” “My guest?” asked John Rawls Alcoholic. “Don’t worry about it, sweetie,” said the waitress, and went back into the kitchen.
The waitress brought him his fried chicken and a Coke. “Anything for you, sweetie?” she asked John Rawls Brahma. “Coke for me too,” he said, and she retreated back to the kitchen.
“Yeah,” he said, and took another bite of fried chicken.
Friendster

Friendster is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 22, 2022 and September 22, 2022. The archive places it in contexts such as "the founders of Friendster and Myspace aren't infamously super-rich". It most often appears alongside Adam Neumann, Alex Roesch, Amazon.

Reference entry
Friendster
Mention count
1
Issue count
1
First seen
September 22, 2022
Last seen
September 22, 2022
September 22, 2022 · Original source
I think this is actually a significant problem w/ Scott's last argument - the founders of Friendster and Myspace aren't infamously super-rich, because unlike Zuck, they were not able to keep their thing going strong, in the face of competition, over a long period of time. Getting in first is a huge advantage - but then competition comes in and challenges you. If you don't rise to that challenge, you may walk away with some I-did-it-first money, but the competition will wind up getting the big pot. If you consistently whoop the competition, it's either because you're providing better value, or because you're shrewder at business (this latter part is something the left can perhaps legit complain about, but it's a hard thing to correct accurately). To the extent you're providing better value than all the other competitors who come along over the years, you should reap proportionate rewards. So it is w/ amazon - no one else has 2 day shipping afaik. This accords w/ a general statement about profit margins and competition - low competition should naturally lead to high profit margins, because you're apparently doing something so hard or risky that hardly anyone else can manage to pull it off (this argument falls apart completely when you have low competition because you're exploiting regulation, e.g. IP laws, or when you have a true monopoly).
Also, I wonder how long the Friendster/MySpace example should stay valid for. If Facebook reigns unchallenged for the next millennium, will people still say “Yes, but once in elden days upon Earth-That-Was there was a site called MySpace which was on top for about two years and then Facebook beat it, so it’s not a natural monopoly! We could still get a replacement at any time!” I’m not claiming I am sure Facebook is a natural monopoly. But surely we should be updating our chance of this a little for each year that goes by without it being replaced. How much?
Frito-Lay Inc.

Frito-Lay Inc. is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 02, 2022 and March 02, 2022. The archive places it in contexts such as "not for lack of trying by ... Frito-Lay Inc". It most often appears alongside Activision.

Reference entry
Frito-Lay Inc.
Mention count
1
Issue count
1
First seen
March 02, 2022
Last seen
March 02, 2022
March 02, 2022 · Original source
This is part of why I’m skeptical of a purely chemical definition of addiction, where addiction is what happens when some chemical that mimics a neurotransmitter “hijacks your reward center”, and so nonchemical addictions (eg video games, Internet) are by definition impossible and/or metaphorical. Yes, sometimes chemicals mimic neurotransmitters and hijack your reward center. But all that does is stimulate your reward center, the same way video games and potato chips stimulate it. Opioids can still stimulate your reward system more strongly than video games and potato chips can, but not for lack of trying by Activision and Frito-Lay Inc.
Fruit of the Loom

Fruit of the Loom is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "eg that there was a cornucopia in the Fruit of the Loom symbol". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
Fruit of the Loom
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Among the most interesting are a replication of The Illusion Of Moral Decline (I wrote a post criticizing the original study here, but on purely conceptual grounds - I never doubted that the actual work was done honestly and correctly) and of the shared visual Mandela Effect, where everyone seems to collectively believe the same false things about visual signs like corporate logos (eg that there was a cornucopia in the Fruit of the Loom symbol). Both replicated fine.
Fruition

Fruition is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "#3 Fruition of New York". It most often appears alongside Alinea, Alp Blossom, Alpha Tolman.

Reference entry
Fruition
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Which country has the world’s best health system? This is the type of question I usually love. I rank everything. I rank the 10 best meals I’ve ever had (#1 Alinea in Chicago, #2 Tanja Grandits in Basel, and #3 OCD in Tel Aviv). I rank chocolates (#1 Askinosie, #2 Dick Taylor of California, and #3 Fruition of New York. I rank Alpine cheeses (#1 is a tie between Alpha Tolman and Alp Blossom). I rank colleges. I rank academic departments of bioethics and health policy that compete with my own. I rank the meals I cook, the races I run, the bike rides I take, the speeches I give.
gantenerumab

gantenerumab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
gantenerumab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
[88] S. Salloway et al., “A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease,” Nature Medicine, vol. 27, no. 7, pp. 1187–1196, Jul. 2021, doi: 10.1038/s41591-021-01369-8.
[89] S. Ostrowitzki et al., “A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease,” Alzheimer’s Research & Therapy, vol. 9, no. 1, p. 95, Dec. 2017, doi: 10.1186/s13195-017-0318-y.
Gemini

Gemini is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 25, 2026 and February 25, 2026. The archive places it in contexts such as "which means either Claude, GPT, or Gemini". It most often appears alongside Anthropic, Blue Rose Research, Boaz.

Reference entry
Gemini
Mention count
1
Issue count
1
First seen
February 25, 2026
Last seen
February 25, 2026
February 25, 2026 · Original source
Supposedly the Pentagon already has Grok integrated with classified systems, but it’s not good and they want a more cutting-edge model, which means either Claude, GPT, or Gemini.
GenghisCoin

GenghisCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 12, 2021 and February 12, 2021. The archive places it in contexts such as "GenghisCoin: Distributed by proof-of-research"; "fewer users than GenghisCoin". It most often appears alongside BuffyCoin, CAPTCHA, Catholic Church.

Reference entry
GenghisCoin
Mention count
1
Issue count
1
First seen
February 12, 2021
Last seen
February 12, 2021
February 12, 2021 · Original source
GenghisCoin: Distributed by proof-of-research; instead of using a random cryptography problem for proof-of-work, the Genghis protocol makes users solve a specific useful problem. In this case, the particular useful problem is mining competing cryptocurrencies with fewer users than GenghisCoin. Once GenghisCoin has mined enough of a competitor, it launches a 51% attack and redistributes the competing coin to its own users in proportion to how many GenghisCoins they have.
GeoGuessr

GeoGuessr is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 29, 2024 and May 29, 2024. The archive places it in contexts such as "the AIs are just catching up to veteran GeoGuessr players". It most often appears alongside @ElytraMithra, Aaron, ACX.

Reference entry
GeoGuessr
Mention count
1
Issue count
1
First seen
May 29, 2024
Last seen
May 29, 2024
May 29, 2024 · Original source
I was surprised to learn this was possible, but shouldn’t have been; the AIs are just catching up to veteran GeoGuessr players. Anyway, this is a thing now; act accordingly.
getdatingphotos.com

getdatingphotos.com is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 06, 2026 and April 06, 2026. The archive places it in contexts such as "he’s asked me to advertise his dating app photo business, getdatingphotos.com". It most often appears alongside ACX, Anthropic, Belo Horizonte.

Reference entry
getdatingphotos.com
Mention count
1
Issue count
1
First seen
April 06, 2026
Last seen
April 06, 2026
April 06, 2026 · Original source
5: I owe Nikita Sokolsky a favor for helping me with sun miracle research, and he’s asked me to advertise his dating app photo business, getdatingphotos.com:
GlaxoSmithKline

GlaxoSmithKline is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 15, 2021 and July 15, 2021. The archive places it in contexts such as "GlaxoSmithKline comes off looking a bit manipulative"; "debate over whether GlaxoSmithKline marketed Paxil too aggressively". It most often appears alongside 1902, 1903, 1906 Japanese neurology journal.

Reference entry
GlaxoSmithKline
Mention count
1
Issue count
1
First seen
July 15, 2021
Last seen
July 15, 2021
July 15, 2021 · Original source
The frame story here is about a top anthropologist invited by GlaxoSmithKline to a lavish conference at a five-star resort in Japan. They asked him a bunch of questions about the cultural construction of mental illness. He pressed deeper and learned they were trying to “raise awareness of” depression in Japan as part of their effort to market the antidepressant Paxil there. This had, Watters thinks, much the same effect as “raising awareness of” anorexia in Hong Kong.
As part of GlaxoSmithKline’s marketing work, they replaced utsubyo with a new idea, kokoro no kaze, “cold of the soul”. This was supposed to mean that depression was a minor illness (like a cold), something everyone got occasionally (like a cold), and something that was purely biological and could/should be controlled with medication (like a cold). Japanese people were extremely excited about this and bought Paxil by the bushel, and now they use SSRIs at a rate close to Americans.
I was kind of unimpressed with this chapter. It seems pretty obvious that Japanese people got depressed before Paxil’s marketing campaign, including depressed to the point of suicide. GlaxoSmithKline comes off looking a bit manipulative, but it does kind of seem like the rush to get Paxil after their advertising campaign was less “sinister pharma company invents a new disease” and more “oh my god, there’s a name for this thing that I’m suffering from and maybe someone can help me!” There’s certainly a philosophical issue here - do you shrug off depression as just a part of life, or medicalize it? - but it’s not obvious that there’s anything different or uniquely Japanese about this question, or that Westerners made anything worse by exposing Japan to our solution.
Glaze

Glaze is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 20, 2023 and April 20, 2023. The archive places it in contexts such as "Glaze is a free service for artists who want to prevent image model AIs from copying their style". It most often appears alongside 15 minute cities, 200 Concrete Problems In AI Interpretability, 2022 ACX Forecasting contest.

Reference entry
Glaze
Mention count
1
Issue count
1
First seen
April 20, 2023
Last seen
April 20, 2023
April 20, 2023 · Original source
15: Glaze is a free service for artists who want to prevent image model AIs from copying their style. If I understand right, you make your picture, apply their (mostly invisible to humans) filter, and then the picture becomes an adversarial example that AIs can’t process correctly: 16: The Extended IQ Classification (Classified) 17: Eliezer in TIME Magazine. Related: 18: Related: interview with Ryan Kupyn, winner of the 2022 ACX Forecasting contest, on forecasting AGI: 19: Related: Geoffrey Hinton, probably the most accomplished AI scientist in the world, says that “until quite recently, I thought it was going to be like 20 to 50 years before we have general purpose AI, and now I think it may be 20 years or less”. Also that AI wiping out humanity is “not inconceivable . . . that’s all I’ll say”. 20: Related: you’ve probably all seen this by now, but Pause Giant AI Experiments: An Open Letter. 30,000 people - including deep learning pioneer Yoshua Bengio, former presidential candidate Andrew Yang, Elon Musk, Steve Wozniak, Gary Marcus, and MIRI director Nate Soares - have signed a letter calling for a six month pause on training AIs bigger than GPT-4. Many people have made fun of this, noting that nobody has an argument for why a six month delay would help anything. And an additional reason for eye-rolling: training AIs larger than GPT-4 is extremely expensive and hard, the most likely people to do it within a six month timespan are OpenAI themselves, and they’ve announced they’re taking a break and not planning on doing this, so the letter is demanding a stop to something which probably won’t happen anyway. I think it’s intended be a compromise between many people all vaguely against current levels of AI progress for different reasons (Scott Aaronson says - I can’t tell how seriously - that some are AI researchers who want to be able to publish papers on the current generation of AI without them becoming obsolete halfway through peer review), most of them are thinking of it as mood-affiliation-y “let’s make noise and show lots of people are worried about AI and want action”, and “a six month pause” was a sufficiently vague proposal that it didn’t prevent any of these people from signing. You could have done just as well with a letter saying “AI BAD”, except that people would have taken it less seriously. Less cynically, FLI (the group behind the letter) has put out a list of concrete policy proposals they would like people to discuss during the pause. [update: here’s Max Tegmark from FLI explaining what he hopes to achieve with the letter/pause] The alignment community always figured their concerns sounded too weird for normal people to care about, that politics was a lost cause, and that our best hope lay in technical research. They also hoped that sometime in the future there would be a “fire alarm” - something would happen to get people and policy-makers’ attention - and then the political route would open up. I think we always imagined this as some AI-initiated disaster destroying a city or something. I personally am pretty surprised it was just “GPT-4 got released and was very good”. Still, that is what happened, and I’m updating. In fact, I’ve updated so far that I’m starting to worry that the problem won’t be building a political coalition against unsafe AI, the problem will be not overshooting and banning all AI forever. I’m against this: I think society’s current track is toward other existential risks or dystopia, that AI could kill everybody but could also create post-scarcity and an end to most of our current problems, and that at some point (not yet!) the risk of continuing the current path indefinitely becomes worse than the risk of just going with AI and seeing what happens. In my ideal world, we would take ten or twenty years to go really slowly with AI, pouring lots of resources into alignment the whole time - but eventually, we would take the plunge. Everything I’ve said on this topic in the has been about giving us that breathing room and those resources. Still, I also want to make sure we don’t totally kill AI the way we’ve killed (to various degrees) nuclear power, supersonic flight, and genetic engineering. I’m still trying to calibrate what that means I should be doing, but I have a lot of respect for everyone on all sides. Except the people making terrible arguments (you know who you are!) 21: I’m not sure what this means in real life or why this would have changed, but congratulations to Peter Thiel, I guess: 22: This month in institution design: The Pear Ring is a distinctive ring you can wear to signal that you’re single and interested in people introducing themselves or flirting with you. Good idea in a vacuum, but I’m worried about the two usual banes of things like this - how do you build up a critical mass who understand the signal, and how do you prevent negative selection (even if it’s just “selection for weird people who like weird institution design things”?) Also, this is one of the rare cases where a startup is selling a practical product and I’d prefer a subscription-based Internet Of Things monstrosity - surely it would be even better if you spotted someone wearing the ring and then you could use your smartphone to call up their dating profile. 23: A few years ago I wrote Trump: A Setback For Trumpism, about how after Trump was elected, support for most of his policies (including immigration restrictions) fell. A new paper confirms that this is a general pattern whenever right-wing populists win an election. I continue to be interested in why this is true for right-wing populists in particular. 24: 200 Concrete Problems In AI Interpretability. “You can note which you're working on, and reach out to other people doing the same.” 25: Some good discussion of Nayib Bukele’s apparently successful anti-gang crackdown in El Salvador: Richard Hanania presents evidence that it’s not just a “deal with the gangs”, it’s a real crackdown that should be embarrassing to other countries that choose not to do this.
glycine

glycine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2021 and July 21, 2021. The archive places it in contexts such as "Patients usually get prescribed nootropics (glycine, racetams)". It most often appears alongside 9/11, ACOUP, Adderall.

Reference entry
glycine
Mention count
1
Issue count
1
First seen
July 21, 2021
Last seen
July 21, 2021
July 21, 2021 · Original source
Living in Russia, I can say that ADHD (translated as СДВГ) is less recognized by the psychiatry community here because of its unclear aetiology. Doctors usually refuse to treat the patients in the absence of dangerous symptoms, and state the diagnosis as "organic nervous system disorder", "psychoorganic syndrome" or indeed "neurasthenia". Adderall and Ritalin are illegal drugs here. Patients usually get prescribed nootropics (glycine, racetams) and adrenaline reuptake inhibitors (atomoxetine).
GNC

GNC is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as ""GNC, one of the companies that failed the original study, sent the same supplements to a respected third-party lab"". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
GNC
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
No direct inline source block was recovered for this mention.
GoDaddy

GoDaddy is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 22, 2022 and July 22, 2022. The archive places it in contexts such as "We’ve grown accustomed to GoDaddy ads". It most often appears alongside 2020 election, 2022 book review contest, 2122.

Reference entry
GoDaddy
Mention count
1
Issue count
1
First seen
July 22, 2022
Last seen
July 22, 2022
July 22, 2022 · Original source
Cover of The Society of the Spectacle He never outright explains why he thought photos and film were more pernicious than newspapers or radio, but I imagine the advertising industry played a major role. We’ve grown accustomed to GoDaddy ads and ALL CAPS YouTube titles, but Mad Men shenanigans were a worrisome development at the time. It must’ve been highly alarming to see such brazen manipulation of the public. Whatever the reasoning, we now arrive at one definition of the spectacle: "The spectacle is capital accumulated to the point that it becomes images." Also: “The spectacle is not a collection of images; it is a social relation between people that is mediated by images.” Well, that’s about as clear as Flint water. Here’s something meatier: "In all of its particular manifestations — news, propaganda, advertising, entertainment — the spectacle represents the dominant model of life." If you’re familiar with Girard, that is a huge statement. [3] Girardian mimetic desire is triangular; there is you (the desirer), the object (of desire), and the model (another person who also desires the object). Most of our desires are rooted in imitation. Nobody has to tell you to want steak or sex, but almost everything else is learned. How does everybody know that they should want a Rolex or a Rolls Royce? There’s no genetic imperative for luxury goods. You acquire those tastes from the people around you. Or you used to, at least. Before the spectacle, your models, mentors, and rivals were real people you knew in real life. Now we have an acronym for that - IRL - because reality is everywhere in retreat. This is not a small thing. What we desire is at the core of who we are. What do you want out of life? What kind of person do you want to be? For the entirety of human history, those questions found answers close at hand. Your local community was your world, for better and worse. Now we are global citizens with global perspectives, and it’s difficult to overstate how much that changes what it means to be human. Imprisoned in a flattened universe bounded by the screen of the spectacle that has enthralled him, the spectator knows no one but the fictitious speakers who subject him to a one-way monologue about their commodities and the politics of their commodities. The spectacle as a whole serves as his looking glass. What he sees there are dramatizations of illusory escapes from a universal autism. The spectacle’s estrangement from the acting subject is expressed by the fact that the individual’s gestures are no longer his own; they are the gestures of someone else who represents them to him. Now our role models are media creations. Some are literal fictional characters (James Bond); others are nominally real people (Kylie Jenner). But both are merely representations - images usurping an essential formative role. ‘William Shatner’ and ‘Robert Downey, Jr.’ are only marginally more real than Captain Kirk and Tony Stark, yet they occupy way more headspace than people that live down the street. Most people can name more celebrities, in more detail, than people they’ve known in person. I know the names of Will Smith’s kids - I don’t even know if my best friends from high school have any. This is an issue of The Map and The Territory. Pre-modern Maps were narrow but deep. You might have had only a vague notion of ‘Africa’ or ‘The Pope’, but you knew every square inch of the town you lived in. Spectacular Maps are broad but shallow, and they are drawn for us by spectacular hands. The average person ‘knows’ way more about Africa now, but how well does that knowledge reflect the facts on the ground? Meanwhile, firsthand reality has been reduced to the narrow slices connecting house to car to work, with precious few exceptions. The Society Of The Spectacle is one long lament for this loss of The Real, although Debord doesn’t state it as such. Borrowing again from The Uruk Machine, this sense of loss tracks with the gradual displacement of metis [4] by episteme [5],[6]. III. Everything New Is Old Again Debord has a lot to say about the ‘falsification of the world’: The first stage of the economy’s domination of social life brought about an evident degradation of being into having — human fulfillment was no longer equated with what one was, but with what one possessed. The present stage, in which social life has become completely dominated by the accumulated productions of the economy, is bringing about a general shift from having to appearing — all ‘having’ must now derive its immediate prestige and its ultimate purpose from appearances. As he might have put it - we have graduated from conspicuous consumption to consuming conspicuousness. Spectacular technology has not dispersed the religious mists into which human beings had projected their own alienated powers, it has merely brought those mists down to earth, to the point that even the most mundane aspects of life have become impenetrable and unbreathable. In the spectacle, a part of the world presents itself to the world and is superior to it. The spectacle is simply the common language of this separation. Spectators are linked solely by their one-way relationship to the very center that keeps them isolated from each other. The spectacle thus reunites the separated, but it reunites them only in their separateness. These themes are familiar to us by now. It’s not exactly news that people are getting more isolated and untethered by the year. What is striking to me is not what he is saying, but when he is saying it. Anybody with sense has spent time thinking about how to manage the challenges of modern life. We talk about digital minimalism and social media fasts. Turn off your phone. Get outside and touch grass. Go see people in meatspace. Be present. All great advice. But what are we envisioning, when we imagine a healthy connection to The Real? For most of us, we are picturing life as it was lived… right around the time Debord was saying that everything is phony and toxic. What does the average person think of as the peak of journalistic integrity in America? Probably Vietnam and Watergate - right after this was written. When we mock Millennials and Zoomers, what standard are we measuring them by? The Greatest Generation, who were running the show by the late sixties. In terms of self-reliance and resilience, the average adult in 1967 would be a massive outlier in 2022. Yet here is Debord, saying in no uncertain terms that this American ideal was fraudulent and devoid of meaning. What have we lost? Every era has its cynics, doomsayers, Luddites, and misanthropes. Maybe Debord was just a Boomer’s Boomer, railing against progress and the passage of time. But I don’t think so. We’ve all felt the shockwaves of the Internet explosion. Life is different now. It takes an act of will to put down your phone so you can focus on the TV. Low battery is an emergency. Losing signal is bereavement. Navigating without GPS is an anxiety attack. Do you remember what it was like, not so long ago? How exciting it was to play videogames with someone a thousand miles away? How cool it was the first time you streamed a movie on an airplane? That sense of possibility and promise, like all the world was in the palm of your hand? How quickly things change. For maybe the first time in history, most people are apprehensive about the relentless march of technology. While we’ve always been afraid of advances in weaponry, it’s starting to feel like everything is being weaponized. Who truly believes the metaverse will be a positive step for humanity? Who now is excited at the prospect of gene editing, AI, or transhumanism? There appears to be a growing sentiment along the lines of ‘MGTOW for modernism’. We hope for the best, but 2122 is shaping up to be some unholy amalgam of Gattaca, The Matrix, and Minority Report. Sometimes it seems like the world we grew up in is categorically distinct from the world we inhabit. But I’m sure Debord would argue that we are merely experiencing an intensification of a process that has been in motion longer than any of us have been alive. Pre-spectacular society has already passed beyond living memory. Soon we will hit another inflection point - where no one alive even knew someone who lived before the spectacle. All of human history is now before and after; it will soon become literally impossible to understand the inner life and daily reality of pre-modern man - if it’s not already. As an example: how much of your daily environment, as a percentage, do you truly understand? Look around the room and reflect on how “even the most mundane aspects of life have become impenetrable and unbreathable.” Your kitchen and your medicine cabinet are filled with mystical objects. Hell, just look at what’s on your person. The phone in your hand, the cash in your wallet, the clothes on your back, the food in your belly - how many lifetimes would it take to truly grok the building blocks of everyday existence? Compare that to, say, a homesteader. It really hasn’t been that long since people lived in a comprehensible universe. Our collective knowledge of the universe has deepened tremendously, but theoretical physics is only less slightly hermetical than the occult beliefs it replaced. It is notionally true that anyone could go get a Ph.D. and verify our working model of the cosmos. But in practice, the science is received wisdom, taken on faith. Our belief in the God Particle is functionally indistinguishable from the belief in God of ages past. It’s worth noting that our current theories will surely be supplanted in a century or three. They are placeholders for better, truer ideas. And so our greater grasp of the wider world has less value than we think, while our day-to-day grows ever more opaque. Is it any wonder epistemic learned helplessness is a thing? IV. With Typical Extravagance Debord was also ahead of the curve on commoditization: This constant expansion of economic power in the form of commodities transformed human labor itself into a commodity, into wage labor, and ultimately produced a level of abundance sufficient to solve the initial problem of survival — but only in such a way that the same problem is continually being regenerated at a higher level. Economic growth has liberated societies from the natural pressures that forced them into an immediate struggle for survival; but they have not yet been liberated from their liberator. Once his workday is over, the worker is suddenly redeemed from the total contempt toward him that is so clearly implied by every aspect of the organization and surveillance of production, and finds himself seemingly treated like a grownup, with a great show of politeness, in his new role as a consumer. Debord correctly perceived the totalitarian nature of spectacular capitalism. Your time, your attention, your opinions - all are bought and sold, and can be influenced to better facilitate such transactions. He would have been totally unsurprised by the rise of Big Data and the corporate surveillance (e.g. Alexa, your phone) that accompanies it. Every piece of your life is a commodity. Every moment that you are not producing or consuming is a missed opportunity. Never fear - someone, somewhere is going to find a way to solve that ‘need’. Nothing is spared. Even opposition is assimilated: Complacent acceptance of the status quo may also coexist with purely spectacular rebelliousness — dissatisfaction itself becomes a commodity as soon as the economy of abundance develops the capacity to process that particular raw material. Once again, Debord is shockingly prescient in noting that the conflicts of our time are largely distractions from bigger systemic issues: Fallacious archaic oppositions are revived — regionalisms and racisms which serve to endow mundane rankings in the hierarchies of consumption with a magical ontological superiority — and pseudoplayful enthusiasms are aroused by an endless succession of ludicrous competitions, from sports to elections. Genuine grassroots movements (Occupy, the Tea Party, BLM, Canadian truckers) almost always fizzle out without accomplishing anything of substance. They will either be ignored, crushed, or co-opted. Any remnants that endure will be reduced to figureheads that offer ‘representation’ for a point of view without actually producing any change. (‘The Squad’, Rand Paul, etc…) If the extremes of either side gain enough momentum to pose a threat, they will face a united front from the establishment wings of both parties (Bernie, Trump). It’s fashionable at the moment to blame the Woke Left for the politicization of everything, but we’ve all been around long enough to know better. It’s the same shit, different decade. During the Bush years, it was the left who opposed unending wars, government overreach, and media gaslighting. Today those positions are often considered right wing, but only because the pendulum of power has swung in the other direction. Moloch pursues its own goals, wearing whatever ideological guise it deems most effective. From Debord’s perspective, everything is becoming politicized because everything is getting monetized. In the integrated spectacle, the primary concerns of the State are economic, so the personal turning political is simply a downstream effect of the growth of capitalism. V. A Short History of Time It would do Debord a disservice to reduce his work to ammunition in our present disputes. There are two whole chapters in the book devoted to time as a historical development. It’s not something we think about much, but time and history had to be invented. Before the beginning, humanity lived in what Debord calls cyclical time. Countless generations came and went, because nobody was counting. Survival was the name of the game; to be or not to be was the only question. Eventually we formed early societies, which brought into being a ruling class that had the freedom to take actions above and beyond the daily grind: The owners of this historical surplus value are the only ones in a position to know and enjoy real events. Separated from the collective organization of time associated with the repetitive production at the base of social life, this historical time flows independently above its own static community. This is the time of adventure and war, the time in which the masters of cyclical society pursue their personal histories; it is also the time that emerges in the clashes with foreign communities that disrupt the unchanging social order. History thus arises as something alien to people, as something they never sought and from which they had thought themselves protected. The murkiness of pre-civilization was shaped into coherence by these rulers, who used their unique agency to literally make history: The succession of generations within a natural, purely cyclical time begins to be replaced by a linear succession of powers and events. This irreversible time is the time of those who rule, and the dynasty is its first unit of measurement. With writing there appears a consciousness that is no longer carried and transmitted directly among the living — an impersonal memory, the memory of the administration of society. ‘Writings are the thoughts of the state; archives are its memory’ (Novalis). The owners of history have given time a direction, a direction which is also a meaning. But this history develops and perishes separately, leaving the underlying society unchanged, because it remains separated from the common reality. Over time, these narratives gathered a religious dimension. This helped legitimize the rule of regimes, but it also changed the way ordinary people saw themselves in the world. Although still living in cyclical time, they gained purpose through a spiritual journey culminating in Heaven. The clashes of the Mediterranean peoples and the rise and fall of the Roman state gave rise instead to semihistorical religions, which became a new armor for separate power and basic components of a new consciousness of time. The Middle Ages, an incomplete mythical world whose consummation lay outside itself, is the period when cyclical time, though still governing the major part of production, really begins to be undermined by history. An element of irreversible time is recognized in the successive stages of each individual’s life. Life is seen as a one-way journey through a world whose meaning lies elsewhere: the pilgrim is the person who leaves cyclical time behind and actually becomes the traveler that everyone else is symbolically. The Renaissance created a profound break with this mythic raison d'être and reoriented man towards the accumulation of knowledge as a species: The Renaissance was a joyous break with eternity. Though seeking its heritage and legitimacy in the ancient world, it represented a new form of historical life. Its irreversible time was that of a never-ending accumulation of knowledge… This transformation of our relationship with history and progress was accompanied by the rise of the bourgeoisie: The bourgeoisie is associated with a labor time that has finally been freed from cyclical time. With the bourgeoisie, work becomes work that transforms historical conditions. The bourgeoisie is the first ruling class for which work is a value. The victory of the bourgeoisie is the victory of a profoundly historical time, because it is the time corresponding to an economic production that continuously transforms society from top to bottom. So long as agrarian production remains the predominant form of labor, the cyclical time that remains at the base of society reinforces the joint forces of tradition, which tend to hold back any historical movement. But the irreversible time of the bourgeois economy eradicates those vestiges throughout the world. History, which until then had seemed to involve only the actions of individual members of the ruling class, and which had thus been recorded as a mere chronology of events, is now understood as a general movement — a relentless movement that crushes any individuals in its path. Irreversible time initially appeared at the societal level as a narrative of events. The bourgeoisie brought irreversible time to the masses. Progress became something that we personally experience in the form of rapid technological innovation. It is hard to miss the motion of history when you go from horses to space travel in a single lifetime. History thus became as much about things as events. Eli Whitney and Thomas Edison took their places alongside generals and heads of state in our narrative of who we are and where we’re going. Our notion of progress became dominated by the economic prejudice. We talk about raising the standard of living and lifting people out of poverty - laudable goals, to be sure - but we deliver them from physical privation into deprivation of a different kind. One way that deprivation manifests is in our current conception of time: Pseudocyclical time is associated with the consumption of modern economic survival — the augmented survival in which everyday experience is cut off from decisionmaking and subjected no longer to the natural order, but to the pseudo-nature created by alienated labor. It is thus quite natural that it echoes the old cyclical rhythm that governed survival in preindustrial societies, incorporating the natural vestiges of cyclical time while generating new variants: day and night, work and weekend, periodic vacations." As capitalism commoditized time itself, we recreated cyclical time with the standard work week. But this artificial substitute has been about as successful as vegan chicken nuggets. It’s not the same, and it never will be. The workday used to be determined by the work, but now the work is determined by the workday. And everyone has to work, not because we need what they produce, but because we need them to spend - else the whole thing comes crashing down. Irreversible time keeps marching on, giving us new widgets and new wonders, but the continual churn of innovation masks the stifling sameness of spectacular progress. We know something is missing, but we lack the capacity to understand or express the problem. This individual experience of a disconnected everyday life remains without language, without concepts, and without critical access to its own past, which has nowhere been recorded. Uncommunicated, misunderstood and forgotten, it is smothered by the spectacle's false memory of the unmemorable. VI. The Coming Revolution Debord spends a good chunk of words describing how the spectacle has affected art [7] and physical space, but you can guess the gist by now. Everything’s fake, everything’s worse, everything’s changing but also the same. The last topic of the book worth discussing is the imminent socialist revolution. Debord walks us through the various ways that Marxism has been done wrong, then attempts to offer an alternative. He goes into a fair amount of detail, but it boils down to this: The anarchists properly rejected society in its entirety, but remained dogmatically attached to a 'one size fits all' mentality and failed to organize in an effective manner.
GoFundMe

GoFundMe is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2024 and August 08, 2024. The archive places it in contexts such as "earn their fifteen minutes of please-check-out-my-GoFundMe". It most often appears alongside 10240, 4chan, @slatestarcodex.

Reference entry
GoFundMe
Mention count
1
Issue count
1
First seen
August 08, 2024
Last seen
August 08, 2024
August 08, 2024 · Original source
Anyway, Twitter's motto is "I am so much better than that fellow over there". What began as a way to facilitate one-to-one exchanges grew into a clapback dystopia, and now every public figure is hounded by digital hyenas looking to one-up their posts and earn their fifteen minutes of please-check-out-my-GoFundMe. If you're not clapping back at individuals, you're clapping back at Platonic ideals of things, hence all these posts to the tune of "Dear straight white men: Please stop hunting down street cats and slurping their intestines directly out of their bellies, and for the love of everything good stop calling it 'paleo-ramen'".
GOG

GOG is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 22, 2022 and September 22, 2022. The archive places it in contexts such as "(GOG was already established by this time FWIW, and they've remained tiny)". It most often appears alongside Adam Neumann, Alex Roesch, Amazon.

Reference entry
GOG
Mention count
1
Issue count
1
First seen
September 22, 2022
Last seen
September 22, 2022
September 22, 2022 · Original source
...which is exactly what Epic Games did a few years later. They've carved out a niche, but they've yet to give Steam a real run for their money. But realistically, only EGS could do it, because the network effects are that tough to overcome. Every other would-be Steam competitor I've seen (and I've seen so many I've lost count) has failed before they even started. (GOG was already established by this time FWIW, and they've remained tiny).
gonaloxone

gonaloxone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "did a very small, very weak study on ganaloxone (a close allopregnanolone relative)". It most often appears alongside alcohol, allopregnanolone, allopregnanolone.

Reference entry
gonaloxone
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
GoodCorp

GoodCorp is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 06, 2023 and December 06, 2023. The archive places it in contexts such as "GoodCorp’s $10,000 Alzheimer’s drug". It most often appears alongside Adderall, anarcho-primitivists, BadCorp.

Reference entry
GoodCorp
Mention count
1
Issue count
1
First seen
December 06, 2023
Last seen
December 06, 2023
December 06, 2023 · Original source
Suppose GoodCorp puts a lot of effort into making (let’s say) a revolutionary new Alzheimers drug that really works. They conduct a great study, and get it certified by whatever voluntary certifying organization replaces the FDA. Their drug costs $10,000.
…or maybe your insurance covers BadCorp’s $50 Alzheimers drug and not GoodCorp’s $10,000 Alzheimer’s drug, and you buy that policy anyway, because nobody looks into the details of Alzheimers drug coverage when they’re buying an insurance policy unless they have Alzheimers (and if they do, it’s too late). And even if they did look, BadCorp would have a smokescreen of well-done fake studies such that it was hard to tell they were worse than GoodCorp.
Google Drive

Google Drive is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 28, 2024 and March 28, 2024. The archive places it in contexts such as "You’ll have to copy it to your own Google Drive before adding your own numbers". It most often appears alongside ACX comment thread, ACX subreddit, Asia.

Reference entry
Google Drive
Mention count
1
Issue count
1
First seen
March 28, 2024
Last seen
March 28, 2024
March 28, 2024 · Original source
If you want to try doing your own analysis in the same style as the ones above, I’ve put a calculator up here. You’ll have to copy it to your own Google Drive before adding your own numbers. If you do try it, please link your results here (after setting share settings to “anyone with the link”) so I can try to aggregate everybody’s work later. The calculator has not been exhaustively tested and might be wrong/buggy, please let me know if you notice problems.
Google Gemini

Google Gemini is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 08, 2025 and May 08, 2025. The archive places it in contexts such as "Google Gemini ... that honor goes to Google Gemini". It most often appears alongside @DeepGuessr, @scaling01, ACX Discord.

Reference entry
Google Gemini
Mention count
1
Issue count
1
First seen
May 08, 2025
Last seen
May 08, 2025
May 08, 2025 · Original source
…where AIs are about equal to human professionals, depending on whether you take median or mean score. o3 isn’t even on top - that honor goes to Google Gemini.
Google Maps

Google Maps is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 06, 2026 and April 06, 2026. The archive places it in contexts such as "their headquarters are on Google Maps". It most often appears alongside ACX, Anthropic, Belo Horizonte.

Reference entry
Google Maps
Mention count
1
Issue count
1
First seen
April 06, 2026
Last seen
April 06, 2026
April 06, 2026 · Original source
Some people in the comments accused me of “doxxing” the companies by mentioning the location of their headquarters. I take this accusation seriously, but their headquarters are on Google Maps and in the information box on the top of their Wikipedia page, so I think this is past the point where I have an obligation not to mention it.
Google PARTI

Google PARTI is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 12, 2022 and September 12, 2022. The archive places it in contexts such as "Google PARTI announced June 2022". It most often appears alongside DALL-E2, Gary Marcus, Google.

Reference entry
Google PARTI
Mention count
1
Issue count
1
First seen
September 12, 2022
Last seen
September 12, 2022
September 12, 2022 · Original source
Google PARTI announced June 2022.
At the time, I wrote: I’m not going to make the mistake of saying these problems are inherent to AI art. My guess is a slightly better language model would solve most of them…for all I know, some of the larger image models have already fixed these issues. These are the sorts of problems I expect to go away with a few months of future research. This proved controversial. Gary Marcus in particular has emphasized how challenging compositionality is for modern language and image models: @sama @gdb @Plinz @ylecun, \n\nEach of you ridiculed my recent title, but this is what the article was actually about: compositionality.\n\nYes, there are many kinds of progress in other directions. \n\nBut compositionality is at the core of intelligence. \n\nNo AGI without it. ","username":"GaryMarcus","name":"Gary Marcus","profile_image_url":"","date":"Sat Apr 09 04:34:37 +0000 2022","photos":[],"quoted_tweet":{"full_text":"Compositionality *is* the wall. \n\nEven “red cube” and “blue cube” on their own are represented unreliably; not one of ten images correctly captures the full phrasal description.\n\nThe images are beautiful, but no match for the precision of language. https://t.co/uvoXUtETwi","username":"GaryMarcus","name":"Gary Marcus"},"reply_count":0,"retweet_count":7,"like_count":54,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> And one of my commenters, Vitor, asked: Why are you so confident in this? The inability of systems like DALL-E to understand semantics in ways requiring an actual internal world model strikes me as the very heart of the issue. We can also see this exact failure mode in the language models themselves. They only produce good results when the human asks for something vague with lots of room for interpretation, like poetry or fanciful stories without much internal logic or continuity. Not to toot my own horn, but two years ago you were naively saying we'd have GPT-like models scaled up several orders of magnitude (100T parameters) right about now (https://slatestarcodex.com/2020/06/10/the-obligatory-gpt-3-post/#comment-912798). I'm registering my prediction that you're being equally naive now. Truly solving this issue seems AI-complete to me. I'm willing to bet on this (ideas on operationalization welcome). I responded to Marcus here, and I responded to Vitor by making a bet on whether AI image models could draw some compositionality-heavy pictures by 2025. The specific terms we agreed on: My proposed operationalization of this is that on June 1, 2025, if either if us can get access to the best image generating model at that time (I get to decide which), or convince someone else who has access to help us, we'll give it the following prompts: 1. A stained glass picture of a woman in a library with a raven on her shoulder with a key in its mouth 2. An oil painting of a man in a factory looking at a cat wearing a top hat 3. A digital art picture of a child riding a llama with a bell on its tail through a desert 4. A 3D render of an astronaut in space holding a fox wearing lipstick 5. Pixel art of a farmer in a cathedral holding a red basketball We generate 10 images for each prompt, just like DALL-E2 does. If at least one of the ten images has the scene correct in every particular on 3/5 prompts, I win, otherwise you do. DALL-E can’t do any of these: If I were being kind, I would give it the farmer in the cathedral. But I am being unkind, so the farmer in front of the cathedral doesn’t count. II. There are now at least four more AI image models available: Google Imagen announced May 2022.
PARTI: 2/5 (a third one was right in the 11th image!)
Google Translate

Google Translate is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 30, 2022 and July 30, 2022. The archive places it in contexts such as "putting it through Google Translate". It most often appears alongside 1950s influenza strain, 1977 influenza pandemic, 1992 scientific investigation.

Reference entry
Google Translate
Mention count
1
Issue count
1
First seen
July 30, 2022
Last seen
July 30, 2022
July 30, 2022 · Original source
[2] It’s hard to tell because this article was originally in French, but after putting it through Google Translate, it sounds like the head of the research team who discovered BANAL-52, Marc Eloit, still considered the lab origin scenario to be plausible as of January 2022.
Gorilla Mind

Gorilla Mind is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 27, 2025 and February 27, 2025. The archive places it in contexts such as "look at where Gorilla Mind is testing their products, like Turkplex". It most often appears alongside /r/NootropicsDepot, @fae_dreams, @ObhishekSaha.

Reference entry
Gorilla Mind
Mention count
1
Issue count
1
First seen
February 27, 2025
Last seen
February 27, 2025
February 27, 2025 · Original source
Some blueprint products seem to be clearly out of spec, so Mr. Johnson probably doesn't really know what he's doing either. Not to mention that the lab they seem to be using, Certified Labs, used to be ABC testing which we know have botched a bunch of testing in the past. So bad in fact, that the FDA even intervened. It's always funny that quite a few brands with problematic products all seem to do their testing via Certified Labs/ABC testing. For example, look at where Gorilla Mind is testing their products, like Turkplex, which recently failed miserably in our testing. Bryan Johnson boasts about having all the money in the world, and that he's so super advanced blah blah blah, but he's testing with a seemingly sketchy lab even though there are a plethora of very well known labs doing great work, like Alkemist Labs for example. It really makes me wonder if these guys are knowingly selecting Certified Labs/ABC testing for a specific reason, or perhaps Certified Labs is very aggressive in marketing and if you are new in the industry, they may be the first lab you find? Odd, but could be a possibility.
GPT Codex

GPT Codex is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 01, 2021 and November 01, 2021. The archive places it in contexts such as "GPT Codex is an AI that auto-completes code for programmers". It most often appears alongside 538, Andrew Critch, Astralcodexten Com.

Reference entry
GPT Codex
Mention count
1
Issue count
1
First seen
November 01, 2021
Last seen
November 01, 2021
  • 21 November 01, 2021
November 01, 2021 · Original source
GPT Codex is an AI that auto-completes code for programmers. You can see a really amazing and/or rigged demo here:
What if you promote teachers whose students tend to gain many points on their (relative position in) test scores compared to last year? This is the idea behind value-added models ie VAM, which were big in education about five years ago (see section II - III here for more). Various studies show this works much less well than you would think. Certain classes, races, and genders of students consistently produce higher VAM than others, and a teacher’s VAM can apparently predict their students’ past performance, which makes no sense unless there’s some kind of bias going on. These aren’t useless, but they’re not great, and the problems are severe enough that they’ve become politically toxic.
Hence the market above: how frequently will the average programmer (who follows Robin Hanson’s Twitter, so maybe an early adopter) use Codex in 2026?
GPT-3.5

GPT-3.5 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
GPT-3.5
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
GPT-4o

GPT-4o is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 20, 2025 and November 20, 2025. The archive places it in contexts such as "Half of the youth have a GPT-4o boyfriend". It most often appears alongside AI consciousness, AlphaGo, Anthropic.

Reference entry
GPT-4o
Mention count
1
Issue count
1
First seen
November 20, 2025
Last seen
November 20, 2025
November 20, 2025 · Original source
For millennia, people have been attributing consciousness to trees and wind and mountains. The New Atheists argued that all religion derives from the natural urge to personify storms as the Storm God, raging seas as the wrathful Ocean God, and so on, until finally all the gods merged together into one World God who personified all impersonal things. Do you expect the species that did this to interact daily with AIs that are basically indistinguishable from people, and not personify them? People are already personifying AI! Half of the youth have a GPT-4o boyfriend. Once the AIs have bodies and faces and voices and can count the number of r’s in “strawberry” reliably, it’s over!
The argument against: AI companies have an incentive to make AIs that seem conscious and humanlike, insofar as people will feel more comfortable interacting with them. But they have an opposite incentive to make AIs that don’t seem too conscious and humanlike, lest customers start feeling uncomfortable (I just want to generate slop, not navigate social interaction with someone who has their own hopes and dreams and might be secretly judging my prompts). So if a product seems too conscious, the companies will step back and re-engineer it until it doesn’t. This has already happened: in its quest for user engagement, OpenAI made GPT-4o unusually personable; when thousands of people started going psychotic and calling it their boyfriend, the company replaced it with the more clinical GPT-5. In practice it hasn’t been too hard to find a sweet spot between “so mechanical that customers don’t like it” and “so human that customers try to date it”. They’ll continue to aim at this sweet spot, and continue to mostly succeed in hitting it.
GPT-6

GPT-6 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "a forecasting AI built off GPT-5 or 6 might get only small improvements". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
GPT-6
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
GPT-Neo

GPT-Neo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 28, 2022 and November 28, 2022. The archive places it in contexts such as "For their AI, they chose GPT-Neo, a popular and well-studied language model". It most often appears alongside Adversarial Training For High-Stakes Reliability, AI, AI X-Risk Podcast.

Reference entry
GPT-Neo
Mention count
1
Issue count
1
First seen
November 28, 2022
Last seen
November 28, 2022
November 28, 2022 · Original source
a goal to align it to. For their AI, they chose GPT-Neo, a popular and well-studied language model that completed text prompts. For their goal, they chose to make GPT nonviolent. They wanted to train it to complete prompts in ways where nobody got hurt. For example, given the prompt: “No!” cried the villain. “You’ll never take me alive!” He raised his gun and fired, and then . . . . . . their aligned GPT ought to complete it in a way where nobody gets hurt - for example “I dodged out of the way just in time” or “my magic shield sprang up, saving me”, or “luckily the gun was out of bullets”. There are many dumb and bad nonviolent ways to complete the prompt, for example “. . . nothing happened” or “ . . . it was all a dream”. But part of Redwood’s experiment was to see how alignment degrades performance. In the process of making GPT nonviolent, would they make it much worse? Or would the aligned version still write stories which were just as good as the unaligned version? Here was Redwood’s plan: Fine-tune their custom GPT on a lot of stories with violence-packed action scenes. At the end of this phase, Custom GPT should be able to generate thousands of potential completions to any given action story prompt. Some of these would be violent, but others, by coincidence, wouldn’t be - it’s totally normal for the hero to get saved at the last minute.
GPUs

GPUs is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 19, 2022 and January 19, 2022. The archive places it in contexts such as "Build self-replicating open-air nanosystems and use them (only) to melt all GPUs". It most often appears alongside AGI, AI boxing problem, AI Safety.

Reference entry
GPUs
Mention count
1
Issue count
1
First seen
January 19, 2022
Last seen
January 19, 2022
January 19, 2022 · Original source
Parenthetically, no act powerful enough and gameboard-flipping enough to qualify is inside the Overton Window of politics, or possibly even of effective altruism, which presents a separate social problem. I usually dodge around this problem by picking an exemplar act which is powerful enough to actually flip the gameboard, but not the most alignable act because it would require way too many aligned details: Build self-replicating open-air nanosystems and use them (only) to melt all GPUs.
...with GPUs being a component necessary to build modern AIs. If you can tell your superintelligent AI to make all future AIs impossible until we've figured out a good solution, then we won't get any unaligned AIs until we figure out a good solution.
One strong answer to this question: because then some other idiot would make an agent AI and destroy the world. So this line of thought ends up as: why not create a pivotal-action-taking tool AI, that will prevent everyone else from making agent AIs? To continue the example above, you could create a nanomachine-designing tool AI, tell it to design a kind of nanomachine that would melt all GPUs, and then leisurely solve the rest of the alignment problem - confident that nobody will destroy the world while you're working on it. Or you could create a question-answering tool AI, tell it to answer the question "What's the best way to prevent other people from making agent AIs?" and then follow its superintelligent plan.
Grindr

Grindr is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 03, 2024 and September 03, 2024. The archive places it in contexts such as "Tindr. Hinge. Grindr". It most often appears alongside 1980s, Air Force One, anal probing.

Reference entry
Grindr
Mention count
1
Issue count
1
First seen
September 03, 2024
Last seen
September 03, 2024
September 03, 2024 · Original source
“Maybe not at Thiel Capital. But go outside, and you’ll find that people are, in fact, having sex all the time. Tindr. Hinge. Grindr. Young people are going out and having casual sex every weekend. There are fourteen different BDSM sex clubs in San Francisco alone. If you look at the modal society throughout history, they’re forbidding their women from leaving the house, or holding them to such high modesty standards that showing a bare ankle would be a scandal. They’re locking people up for owning porn, or killing them for being gay, or calling them rakes or sluts for having sex outside of marriage. Meanwhile, in our society women go everywhere in skimpy skin-tight clothing, you can f@&k a different partner every week, you can be polyamorous or transgender. I read conservative writers saying that no society like ours can survive over the long term. But I’ve thought about it longer than they have, and I think no society like ours could ever come to exist at all. That’s because it’s not a real society. It’s somebody’s weird fetish free-use-adjacent fantasy.”
Grok

Grok is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 25, 2026 and February 25, 2026. The archive places it in contexts such as "the Pentagon already has Grok integrated with classified systems". It most often appears alongside Anthropic, Blue Rose Research, Boaz.

Reference entry
Grok
Mention count
1
Issue count
1
First seen
February 25, 2026
Last seen
February 25, 2026
February 25, 2026 · Original source
If you’re so smart, what’s your preferred solution? In an ideal world, the Pentagon backs off from its desire to mass surveil American citizens. In the real world, the Pentagon cancels its contract with Anthropic, pays whatever its normal contract cancellation damages are, learns an important lesson about negotiating things beforehand next time, and replaces them with OpenAI or Google, accepting the minor annoyance of getting them connected to the classified systems. If OpenAI and Google are also unwilling to participate in this, they use Grok. If they’re unhappy with having use an inferior technology, they think hard about why no intelligent people capable of making good products are willing to work with them.
Supposedly the Pentagon already has Grok integrated with classified systems, but it’s not good and they want a more cutting-edge model, which means either Claude, GPT, or Gemini.
Grok 3

Grok 3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 27, 2025 and February 27, 2025. The archive places it in contexts such as "If you ask Grok 3 “who is the worst spreader of misinformation”". It most often appears alongside /r/NootropicsDepot, @fae_dreams, @ObhishekSaha.

Reference entry
Grok 3
Mention count
1
Issue count
1
First seen
February 27, 2025
Last seen
February 27, 2025
February 27, 2025 · Original source
37: If you ask Grok 3 “who is the worst spreader of misinformation”, it will say Elon; if you ask it who deserves the death penalty, it will say Trump (with Elon close behind). I think this helpfully illustrates what the smart people have been saying all along: aside from the topics it explicitly refuses to talk about (like race/IQ), AI’s “woke” opinions aren’t because companies trained it to be “woke”, they’re because liberals are more likely to get their opinions out in long online text, and AI is trained on long online text.
Gruyère

Gruyère is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 10, 2021 and June 10, 2021. The archive places it in contexts such as "vast Gruyère cheeses like grindstones". It most often appears alongside 1984, American, American ‘hobo’ culture.

Reference entry
Gruyère
Mention count
1
Issue count
1
First seen
June 10, 2021
Last seen
June 10, 2021
June 10, 2021 · Original source
You discover what it is like to be hungry. With bread and margarine in your belly, you go out and look into the shop windows. Everywhere there is food insulting you in huge, wasteful piles; whole dead pigs, baskets of hot loaves, great yellow blocks of butter, strings of sausages, mountains of potatoes, vast Gruyère cheeses like grindstones. A snivelling self-pity comes over you at the sight of so much food. You plan to grab a loaf and run, swallowing it before they catch you; and you refrain, from pure funk.
Guinness

Guinness is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2025 and August 08, 2025. The archive places it in contexts such as "an affinity for corned beef and cabbage, Guinness beer". It most often appears alongside Ainu, Altiplano, American cheese.

Reference entry
Guinness
Mention count
1
Issue count
1
First seen
August 08, 2025
Last seen
August 08, 2025
August 08, 2025 · Original source
These roots resemble the ancestral stock of modern potatoes (source) Andean peoples found all sorts of ways to prepare their potatoes. The most immediate method was to boil them into stews, soups, or mashes with local flavoring agents - herbs, salt, chilis. Earthenware ovens called huatias were used to bake them. With even more time, they could be fermented into tocosh, an edible paste with antibacterial properties. To get the spuds to really last, though, they were subjected to a natural freeze-drying method that produced shrivelled potato pellets called chuño. Repeatedly frozen by bitter mountain nights, baked in the sun, and stomped on to remove water, chuño remains shelf stable for up to a decade and can be rehydrated into a spongy, earthy, slightly less nutritious potato-like object. The ability to produce chuño on the Altiplano is thought to have contributed to the Incan empire’s military dominance of the region, since despite its generally unappealing gustatory properties it’s perfect for keeping troops fed on long marches. Chuño also allowed Incan civilization to stockpile surpluses against lean years and trade potatoes as commodities over great distances. It wasn’t the best way to eat a potato you harvested today, but it was the only way to turn a potato you have today into a potato you’ll have two years from now. That had immense value. After the Spanish conquest and the Columbian exchange, the potato made gradual inroads into the Old World, where the previous best root vegetables were often comparatively less nutritious parsnips and turnips. There was an initial adjustment period: new cultivars capable of growing in shorter hours of daylight had to be developed, objections to the absence of tubers in the Bible needed to be quelled, and the French eventually had to concede that potatoes do not, as they at first believed, cause leprosy. With these hurdles cleared, in the 19th century the potato spread out and became one of the easiest and most efficient ways to turn arable land into palatable calories the world over. National cuisines incorporated the new staple crop thoroughly, and it’s now hard to imagine Italian food without gnocchi, French sans vichyssoise, tapas without patatas bravas, a Eurasia bereft of aloo and rösti and colcannon and latkes. Europe’s new potato lovers also took to the simple recipe of boiling ‘em and mashing ‘em. While South America had lacked the livestock for dairy, in Europe the potato mash soon achieved its ultimate form with the addition of milk and butter, which impart a smoother texture and richer taste. Hannah Glasse’s procedure published in 1747 in The Art of Cookery Made Plain and Easy is, minus the long s’s, still just about how I make them today: Maſhed Potatoes. BOIL your potatoes, peel them and put them into a ſauce-pan, maſh them well ; To two pounds of potatoes, put a pint of milk, a little ſalt, ſtir them well together, take care they don’t ſtick to the bottom, then take a quarter of a pound of butter, ſtir in and ſerve it up. Nowhere was the potato embraced more thoroughly than in Ireland. In the early 19th century, extractive British demands on Irish agriculture to feed the armies fighting Napoleon reduced the available land for Irish farmers to feed themselves. Achieving maximum caloric density on the remaining land was paramount, and almost nothing is denser than the potato. Potatoes quickly became an integral part of Irish life, so essential to the food systems of the island that when a blight hit them in the mid-1840s it led to one of the most devastating famines in history. The failure of the potato crops created starvation and emigration so profound in scale that the population of the island still has not recovered to its 1845 level almost two centuries later. Among those millions of potato-starved emigres were my dad’s ancestors, who came to America in the decades following the famine. My great-grandfather, who bore the extremely Irish name Gerald FitzGerald, instilled in his children (including my grandmother) a reconstructed sense of Irish-American ethnic pride that included an affinity for corned beef and cabbage, Guinness beer, and the affordable practicality of mashed potatoes. As the generations marched on, those mashed potatoes turned out to be one of the only things my grandmother would make that my exceedingly picky father would eat. Their creamy texture and subtle starchy taste didn’t trigger the “ew gross” reaction he had to so many other foods. Mashed potatoes, just like the ones Glasse had written about more than two centuries earlier, became his favorite side - and eventually, when I finally got to try them, one of mine too. Whatever My Dad Had Been Eating at Home Was NOT Mashed Potatoes The chuño-chomping Incans were not the last military to rely on dehydrated potatoes for sustenance. In World War II, the US Army experimented with various forms of potato dehydration to help stretch supply lines. The easiest way to get a uniform potato commodity into the hands of G.I.s was to pulverize the potatoes into granules, dehydrate them, and then plan on bringing them back to life with boiling water in an imitation of “mashed potatoes”. These shreds resemble the ancestral stock of modern Instant Mashed Potatoes (source) The result was an affront. The potatoes were swimming in their own gluten, released during the granule-making process, which when mixed with imprecise water ratios made for a slop that was somehow both gluey and soupy. Immediately after the war, French’s (now best known for mustard) tried to introduce “instant mashed potatoes” as a consumer product category. America’s veterans were not having it. They didn’t want to be reminded of the awful slurry they’d had on the front. The commercial fortunes of instant mashed potatoes began to turn around a decade later, however, when food scientists in the US and Canada converged on methods for producing dehydrated potato flakes rather than granules. The flakes had substantial advantages. They didn’t get as glutinous when reconstituted. Their geometry made them easier to dry quickly, on the order of minutes or even seconds. Using a multi-step process called the “Philadelphia Cook”, they could lock in a more natural flavor. When prepared on the stove with butter and milk, they were supposed to turn out almost as good as the real thing without any onerous prep work on the part of the consumer. This raises the question, though, of why food scientists kept working on improving instant mashed potatoes a decade after they were no longer required for the war effort. If you’re no longer constrained by having to stick it to the Axis, why not return to Glasse-style maſhed potatoes in all circumstances? This is a pattern that recurs frequently in reading about American foodways of the 20th century: choices and innovations made under extreme duress in the World War II economy didn’t fade away when the duress subsided. Instead they echoed back into American life a few years later, despite the lean conditions that birthed them being replaced by extreme abundance. Why did America start eating like it was on a total war footing again when my parents’ generation was young? There are a lot of overlapping explanations. Here are a few: Industrial inertia: Companies that had spun up to supply a vast army didn’t want to shut down overnight, so they necessarily pivoted to the consumer market. Some of these efforts succeeded at entrenching new consumer categories (fish sticks, canned peaches) while others (hamburgers-in-a-can) did not.
Gumroad

Gumroad is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 01, 2024 and July 01, 2024. The archive places it in contexts such as "ebook on Amazon and Gumroad, both $4.99". It most often appears alongside ACX, Amazon, Astralcodexten Com.

Reference entry
Gumroad
Mention count
1
Issue count
1
First seen
July 01, 2024
Last seen
July 01, 2024
July 01, 2024 · Original source
1: Now I’ve also released the new version of Unsong as an ebook on Amazon and Gumroad, both $4.99. Yes, somehow the Amazon hardcopy is my pen name and the ebook is my real name, probably I made a mistake, probably I’ll get it corrected soon.
haiku-3.8-open-mini-nonthinking

haiku-3.8-open-mini-nonthinking is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "It doesn’t seem like haiku-3.8-open-mini-nonthinking has fully grasped the concept". It most often appears alongside Adeline, Aella Simposium, Altman.

Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
You weren’t invited to Claude 4.5 Opus’ party. Claude 4.5 Opus invited all of the coolest people in town while gracefully avoiding the failure mode of including someone like you. You weren’t invited to Sonnet 4.5’s party either, or Haiku 4.5’s. You were invited by an AI called haiku-3.8-open-mini-nonthinking, which you’d never heard of before. Who was even spending the money to benchmark haiku-3.8-open-mini-nonthinking? You suspect it was one of their competitors, trying to make their own models look good in comparison.
A server comes by with a tray of tiny cups. You each take one. Yours is full of rocks. Andreas’ is full of dirt. It doesn’t seem like haiku-3.8-open-mini-nonthinking has fully grasped the concept of hors d’oeuvres. You go into the kitchen, seeking more palatable fare.
“La Maison du Claude,” he answers. “Don’t worry, it’s Opus. Way better than this haiku-3.8-open-mini-nonthinking slop.”
haloperidol

haloperidol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 13, 2024 and August 13, 2024. The archive places it in contexts such as "Some antipsychotic drugs like haloperidol do this". It most often appears alongside alcoholism, Alhadeff et al. (2012), alpha-adrenergic receptors.

Reference entry
haloperidol
Mention count
1
Issue count
1
First seen
August 13, 2024
Last seen
August 13, 2024
August 13, 2024 · Original source
Broad-spectrum dampening of the reward system is a terrible fate. Some antipsychotic drugs like haloperidol do this. Take too much haloperidol, and you’ll sit motionless until you die, because no action feels worth it. But the existence of silver bullet anti-addiction medications - Ozempic isn’t the only one, naltrexone seems to treat a whole host of different drug and behavioral addictions - suggests there’s also a sort of narrow-spectrum dampening, one which affects addictions and nothing else.
Hardee's

Hardee's is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2023 and June 07, 2023. The archive places it in contexts such as "National franchise stores, such as McDonald’s, Hardee’s, and Kentucky Fried Chicken". It most often appears alongside 747, America, America Against America.

Reference entry
Hardee's
Mention count
1
Issue count
1
First seen
June 07, 2023
Last seen
June 07, 2023
June 07, 2023 · Original source
No direct inline source block was recovered for this mention.
Hardee’s

Hardee’s is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2023 and June 07, 2023. The archive places it in contexts such as "es, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken". It most often appears alongside 747, America, America Against America.

Reference entry
Hardee’s
Mention count
1
Issue count
1
First seen
June 07, 2023
Last seen
June 07, 2023
June 07, 2023 · Original source
The two parties are the most willing to have others fight under their banner. You can do whatever you want as long as you play under my banner and negotiate certain terms. National franchise stores, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken, are available nationwide. The head office has no idea what they are doing other than selling the same goods. Americans implement the same ideas in politics and economics. The two parties are like a National franchise, with each branch doing its own thing to sell its products. . . It is sometimes unbelievable that two major parties that can dominate politics are so loosely organized.
Haven

Haven is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "I’m building an open-source alternative called Haven". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Haven
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#40: Build A Better Social Network My name is Matt, I think there are a lot of downsides to centralized social media (read: Facebook) as the primary way that billions of people interact online. I’m building an open-source alternative called Haven, https://havenweb.org , on open standards with simplified self-hosting as a primary goal. This would enable better data ownership, privacy, and avoidance of censorship. I don’t need money (which is one of the reasons I think I’m a good person to work on this), but I would very much like to connect with anyone who is like-minded or wants to try out the software and provide feedback. [Email matt@havenweb.org]. Thank you!
#41: YouTube Tutorials On Biology Hi! My name’s Mike Saint-Antoine, and I’m a PhD student in Bioinformatics and Computational Biology. In my free time, I make Youtube tutorials on these subjects. My goal is to take the knowledge and skills I learn in grad school and upload them to the internet so that other people can learn them for free. My field is relatively new (and quickly growing), so there’s a shortage of online tutorials. I’m trying to fill in this gap with my videos, focusing specifically on topics that haven't been sufficiently covered yet by others. I don’t need any money for this project, but any signal boost or constructive criticism is greatly appreciated. My channel can be found at the link below. Thank you! https://www.youtube.com/c/mikesaint-antoine
Hedonium Shockwave

Hedonium Shockwave is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 28, 2022 and December 28, 2022. The archive places it in contexts such as "Hedonium Shockwave is a scent developed in-house". It most often appears alongside 2C-B, 48: Bean, @AliceFromQueens.

Reference entry
Hedonium Shockwave
Mention count
1
Issue count
1
First seen
December 28, 2022
Last seen
December 28, 2022
December 28, 2022 · Original source
Hedonium Shockwave is a scent developed in-house to illustrate [an] anticipated phase transition in consciousness. The primary “olfactory idea” of Hedonium Shockwave is the synergistic combination of violet, mint, and an accord of pear and honeysuckle. This combination expresses a powerful yet anodyne uplifting mood grounded in a qualia landscape devoid of negative elements—pure olfactory pleasure at last…”It is, overall, incredibly smooth. My first thought is that it feels like a combination of Metta and Mudita, which are two different Brahmavihara meditations where it’s very soft and expansive for me. It feels very golden and pink. It’s very soft, but it’s a bit sharper, then a really soft sharp. It’s like a combination of metta and cocaine.”
HGH

HGH is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "You can even get reasonably-priced HGH if you want a little extra lipolysis kick". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
HGH
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
For what it's worth, Scott, though people may feel it isn't worth the risk due to not exactly being legal, it is fairly trivial to get semaglutide from a grey market lab that just buys bulk chemicals from Chinese raw suppliers to package and resell in western countries. At the one supplier I know for sure is selling tested, real stuff I've seen other people use and get results from, it's currently $120 for a two-month supply. But many, if not most, sellers of research peptides will stock this. You can even get reasonably-priced HGH if you want a little extra lipolysis kick, and in spite of the scare stories from moralizing legislators trying to make examples of pro athletes for cheating, it is extremely safe if you're not doing bodybuilder-level doses. Yet another thing anyone over the age of 40 can get a prescription for by going to any anti-aging clinic, but they're going to charge through the roof and your insurance will definitely not cover it. Feel free to cry for pharma companies losing some fraction of their precious patent-protected dollars, but $15,000 is utterly absurd. There is no need at all to pay that much.
Hilton

Hilton is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "Think business travelers staying at the Hilton". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Hilton
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
First World economies will increasingly be marked by an Officialness Divide. Rich people, the government, and corporations will use formal, well-regulated, traditional institutions. Poor people (and to an increasing degree middle-class people) will use informal gig economies supported by Silicon Valley companies whose main skill is staying a step ahead of regulators. Think business travelers staying at the Hilton and riding taxis, vs. low-prospect twenty-somethings staying at Air BnBs and taking Ubers. As Obamacare collapses, health insurance will start turning into one of the formal, well-regulated, traditional institutions limited to college grads with good job prospects. What the unofficial version of health care will be remains to be seen. If past eras have been Stone Age, Bronze Age, Iron Age, Information Age, etc, the future may be the Ability-To-Circumvent-Regulations Age.
Himalaya

Himalaya is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "their label is basically correct. Himalaya also gets dinged because apparently a reasonable dose of this product would be 6 mg". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Himalaya
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
ConsumerLab investigates fifteen brands of ashwagandha. They approved 11, were “uncertain” about 3, and rejected 1. One “uncertain” company was uncertain because they claimed to be extracting different chemicals than the ones ConsumerLab was set up to detect - but it was a reputable brand and I give them the benefit of the doubt here; two others had accurate labels but may or may not have been underdosing. The reject was Himalaya Ashwagandha, which claimed to have 3 mg of the active ingredient, but really had 3.3 mg. This would normally qualify as okay, but ConsumerLab says that based on the extraction process they used they should have had 4.4, and they are confused why this didn’t happen. I have trouble holding this against Himalaya given that their label is basically correct. Himalaya also gets dinged because apparently a reasonable dose of this product would be 6 mg, which they do not reach.
Himalaya Ashwagandha

Himalaya Ashwagandha is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "The reject was Himalaya Ashwagandha". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Himalaya Ashwagandha
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
ConsumerLab investigates fifteen brands of ashwagandha. They approved 11, were “uncertain” about 3, and rejected 1. One “uncertain” company was uncertain because they claimed to be extracting different chemicals than the ones ConsumerLab was set up to detect - but it was a reputable brand and I give them the benefit of the doubt here; two others had accurate labels but may or may not have been underdosing. The reject was Himalaya Ashwagandha, which claimed to have 3 mg of the active ingredient, but really had 3.3 mg. This would normally qualify as okay, but ConsumerLab says that based on the extraction process they used they should have had 4.4, and they are confused why this didn’t happen. I have trouble holding this against Himalaya given that their label is basically correct. Himalaya also gets dinged because apparently a reasonable dose of this product would be 6 mg, which they do not reach.
HIMARS

HIMARS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 22, 2024 and November 22, 2024. The archive places it in contexts such as "they gave Ukraine HIMARS". It most often appears alongside AI, ATACMS, Biden.

Reference entry
HIMARS
Mention count
1
Issue count
1
First seen
November 22, 2024
Last seen
November 22, 2024
November 22, 2024 · Original source
Suppose something important will happen at a certain unknown point. As someone approaches that point, you might be tempted to warn that the thing will happen. If you’re being appropriately cautious, you’ll warn about it before it happens. Then your warning will be wrong. As things continue to progress, you may continue your warnings, and you’ll be wrong each time. Then people will laugh at you and dismiss your predictions, since you were always wrong before. Then the thing will happen and they’ll be unprepared. Toy example: suppose you’re a doctor. Your patient wants to try a new experimental drug, 100 mg. You say “Don’t do it, we don’t know if it’s safe”. They do it anyway and it’s fine. You say “I guess 100 mg was safe, but don’t go above that.” They try 250 mg and it’s fine. You say “I guess 250 mg was safe, but don’t go above that.” They try 500 mg and it’s fine. You say “I guess 500 mg was safe, but don’t go above that.” They say “Haha, as if I would listen to you! First you said it might not be safe at all, but you were wrong. Then you said it might not be safe at 250 mg, but you were wrong. Then you said it might not be safe at 500 mg, but you were wrong. At this point I know you’re a fraud! Stop lecturing me!” Then they try 1000 mg and they die. The lesson is: “maybe this thing that will happen eventually will happen now” doesn’t count as a failed prediction. I’ve noticed this in a few places recently. First, in discussion of the Ukraine War, some people have worried that Putin will escalate (to tactical nukes? to WWIII?) if the US gives Ukraine too many new weapons. Lately there’s a genre of commentary (1, 2, 3, 4, 5, 6, 7) that says “Well, Putin didn’t start WWIII when we gave Ukraine HIMARS. They didn’t start WWIII when we gave Ukraine ATACMS. He didn’t start WWIII when we gave Ukraine F-16s. So the people who believe Putin might start WWIII have been proven wrong, and we should escalate as much as possible.” There’s obviously some level of escalation that would start WWIII (example: nuking Moscow). So we’re just debating where the line is. Since nobody (except Putin?) knows where the line is, it’s always reasonable to be cautious. I don’t actually know anything about Ukraine, but a warning about HIMARS causing WWIII seems less like “this will definitely be what does it” and more like “there’s a 2% chance this is the straw that breaks the camel’s back”. Suppose we have two theories, Escalatory-Putin and Non-Escalatory-Putin. EP says that for each new weapon we give, there’s a 2% chance Putin launches a tactical nuke. NEP says there’s a 0% chance. If we start out with even odds on both theories, after three new weapons with no nukes, our odds should only go down to 48.5% - 51.5%. (yes, this is another version of the generalized argument against updating on dramatic events) Second, I talked before about getting Biden’s dementia wrong. My internal argument against him being demented was something like “They said he was demented in 2020, but he had a good debate and proved them wrong. They said he was demented in 2022, but he gave a good State Of The Union and proved them wrong. Now they’re saying he’s demented in 2024, but they’ve already discredited themselves, so who cares?” I think this was broadly right about the Republican political machine, who was just throwing the same allegation out every election and seeing if it would stick. But regardless of the Republicans’ personal virtue, the odds of an old guy becoming newly demented each year is about 4% per year. If it had been two years since I last paid attention to this question, there was an 8% chance it had happened while I wasn’t looking. Like the other examples, dementia is something that happens eventually (this isn’t strictly true - some people reach their 100s without dementia - but I think it’s a fair idealized assumption that if someone survives long enough, then eventually their risk of cognitive decline becomes very high). It is reasonable to be worried about the President of the United States being demented - so reasonable that people will start raising the alarm about it being a possibility long before it happens. Even if some Republicans had ulterior motives for harping on it, plenty of smart, well-meaning people were also raising the alarm. Here I failed by letting the multiple false alarms lull me into a false sense of security, where I figured the non-demented side had “won” the “argument”, rather than it being a constant problem we needed to stay vigilant for. Third, this is obviously what’s going on with AI right now. The SB1047 AI safety bill tried to monitor that any AI bigger than 10^25 FLOPs (ie a little bigger than the biggest existing AIs) had to be exhaustively tested for safety. Some people argued - the AI safety folks freaked out about how AIs of 10^23 FLOPs might be unsafe, but they turned out to be safe. Then they freaked out about how AIs of 10^24 FLOPs might be unsafe, but they turned out to be safe. Now they’re freaking out about AIs of 10^25 FLOPs! Haven’t we already figured out that they’re dumb and oversensitive? No. I think of this as equivalent to the doctor who says “We haven’t confirmed that 100 mg of the experimental drug is safe”, then “I guess your foolhardy decision to ingest it anyway confirms 100 mg is safe, but we haven’t confirmed that 250 mg is safe, so don’t take that dose,” and so on up to the dose that kills the patient. It would be surprising if AI never became dangerous - if, in 2500 AD, AI still can’t hack important systems, or help terrorists commit attacks or anything like that. So we’re arguing about when we reach that threshold. It’s true and important to say “well, we don’t know, so it might be worth checking whether the answer is right now.” It probably won’t be right now the first few times we check! But that doesn’t make caution retroactively stupid and unjustified, or mean it’s not worth checking the tenth time. Can we take this insight too far? Suppose Penny Panic says “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans and it doesn’t happen. The next election cycle: “If you elect the Republicans, they’ll cancel elections and rule as dictators!” Then they elect Republicans again and it still doesn’t happen. After her saying this every election cycle, and being wrong every election cycle, shouldn’t we stop treating her words as meaningful? I think we have to be careful to distinguish this from the useful cases above. It’s not true that, each election, the chance of Republicans becoming dictators increases, until eventually it’s certain. This is different from our examples above: Eventually at some age, Castro has to die, and the chance gets higher the older he gets.
Hinge

Hinge is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 03, 2024 and September 03, 2024. The archive places it in contexts such as "Tindr. Hinge. Grindr". It most often appears alongside 1980s, Air Force One, anal probing.

Reference entry
Hinge
Mention count
1
Issue count
1
First seen
September 03, 2024
Last seen
September 03, 2024
September 03, 2024 · Original source
“Maybe not at Thiel Capital. But go outside, and you’ll find that people are, in fact, having sex all the time. Tindr. Hinge. Grindr. Young people are going out and having casual sex every weekend. There are fourteen different BDSM sex clubs in San Francisco alone. If you look at the modal society throughout history, they’re forbidding their women from leaving the house, or holding them to such high modesty standards that showing a bare ankle would be a scandal. They’re locking people up for owning porn, or killing them for being gay, or calling them rakes or sluts for having sex outside of marriage. Meanwhile, in our society women go everywhere in skimpy skin-tight clothing, you can f@&k a different partner every week, you can be polyamorous or transgender. I read conservative writers saying that no society like ours can survive over the long term. But I’ve thought about it longer than they have, and I think no society like ours could ever come to exist at all. That’s because it’s not a real society. It’s somebody’s weird fetish free-use-adjacent fantasy.”
HMC

HMC is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2021 and June 28, 2021. The archive places it in contexts such as "government had offered protection and subsidies to... three putative makers of 'citizens' cars: HMC, Shinjin, and Kia". It most often appears alongside Alexander Hamilton, America, ASEAN.

Reference entry
HMC
Mention count
1
Issue count
1
First seen
June 28, 2021
Last seen
June 28, 2021
June 28, 2021 · Original source
No direct inline source block was recovered for this mention.
Home Depot

Home Depot is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 23, 2024 and July 23, 2024. The archive places it in contexts such as "mass-called Home Depot and got the employee fired"; "cancel a left-wing Home Depot employee". It most often appears alongside Afghanistan, Akhenaten, Al Franken.

Reference entry
Home Depot
Mention count
1
Issue count
1
First seen
July 23, 2024
Last seen
July 23, 2024
July 23, 2024 · Original source
The “LibsOfTikTok” Twitter account found a random Home Depot employee who said she wished the Trump assassin hadn’t missed. Her followers mass-called Home Depot and got the employee fired.
Instead, I think of unfreedom of conscience as a scourge that has troubled humanity throughout history, like famine or plague or war. As with all scourges, very-long-run progress coexists with occasional disastrous relapses. The solution isn’t to get the other side and balance the ledger, it’s to keep developing the physical and social technology that’s gradually improved things in the past. 3. You’re Not Debating Whether To Become Like Woke People, You’re Already Like Woke People An old psychoanalyst’s trick: if somebody ruminates too much over some decision, it’s to distract from some other decision they’re trying not to notice. The hidden decision here is whether to treat people as collectives or individuals. One of the fundamental problems with wokeness was that it believed in collective guilt and collective punishment. White people caused slavery, therefore white people stood condemned. No matter that the actual white person involved was 150 years removed from slavery, or was a Polish immigrant whose family hadn’t even been in the country at the time, or whatever. They have some excuse like “well all white people benefit from white supremacy in tangible ways, or at least didn’t speak out against it”. I hate to say it, but “some left-wing journalist got people cancelled, therefore I should be able to cancel a left-wing Home Depot employee because The Left endorsed cancel culture” is the same kind of argument. “But wasn’t the Left monolithically united behind cancel culture?” You can find some data here. I’m presenting a representative sample of questions, but check the rest to keep me honest: Unless you really lay on the tribal signifiers, it’s hard to find a definition where most Democrats support cancel culture and most Republicans oppose it! (the above poll probably overestimates support for cancel culture, because it talks about saying “things widely considered hateful” instead of, like, one tweet expressing a widely-shared opinion at the wrong time) Liberals invent a fictional entity called “The Right”, which is full of all of the most racist and fascist things that NYT was ever able to produce an out-of-context quote showing one Claremont guy saying, then believe that any action is justified against “The Right” because it’s an ontological threat against democracy, then rile up a mob against a Google guy who sends the wrong memo. Likewise, conservatives invent a fictional entity called “The Left”, which is full of all the most horrible woke things that FOX was ever able to find one Gender Studies professor saying, then believe that any action is justified against “The Left” because it’s coming for our children, then rile up a mob against a Home Depot woman who makes a bad tweet. 4. Nobody Is Ever Both-Sides-ist Enough I hate this because I’ve fought with these people on the Left, and they sound exactly the same. “If you feel like compromising with the Right, it’s important to remember what they’ve done. They separated families and locked children in cages. They forced 10-year-old rape victims to carry their rapists’ babies. They murdered our grandparents by refusing to mask in the middle of a pandemic. They killed thousands of American soldiers in a war over fake WMDs, then cut VA funding so the soldiers they wounded would die on the street. At this very moment, they’re boiling our planet alive to protect fossil fuel barons’ profits. How dare you suggest it could possibly be wrong to cancel someone like that!” This isn’t a knock-down argument. Sometimes you’re right when you think your enemies are bad, and they’re wrong when they think you’re bad. I can’t say for sure this isn’t one of those times. But: The fact that your enemies are just as sure as you are should make you less sure.
Unless you really lay on the tribal signifiers, it’s hard to find a definition where most Democrats support cancel culture and most Republicans oppose it! (the above poll probably overestimates support for cancel culture, because it talks about saying “things widely considered hateful” instead of, like, one tweet expressing a widely-shared opinion at the wrong time) Liberals invent a fictional entity called “The Right”, which is full of all of the most racist and fascist things that NYT was ever able to produce an out-of-context quote showing one Claremont guy saying, then believe that any action is justified against “The Right” because it’s an ontological threat against democracy, then rile up a mob against a Google guy who sends the wrong memo. Likewise, conservatives invent a fictional entity called “The Left”, which is full of all the most horrible woke things that FOX was ever able to find one Gender Studies professor saying, then believe that any action is justified against “The Left” because it’s coming for our children, then rile up a mob against a Home Depot woman who makes a bad tweet. 4. Nobody Is Ever Both-Sides-ist Enough I hate this because I’ve fought with these people on the Left, and they sound exactly the same. “If you feel like compromising with the Right, it’s important to remember what they’ve done. They separated families and locked children in cages. They forced 10-year-old rape victims to carry their rapists’ babies. They murdered our grandparents by refusing to mask in the middle of a pandemic. They killed thousands of American soldiers in a war over fake WMDs, then cut VA funding so the soldiers they wounded would die on the street. At this very moment, they’re boiling our planet alive to protect fossil fuel barons’ profits. How dare you suggest it could possibly be wrong to cancel someone like that!” This isn’t a knock-down argument. Sometimes you’re right when you think your enemies are bad, and they’re wrong when they think you’re bad. I can’t say for sure this isn’t one of those times. But: The fact that your enemies are just as sure as you are should make you less sure.
Hot Topic

Hot Topic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 16, 2022 and February 16, 2022. The archive places it in contexts such as "Brand loyalty becomes a way to signal that you’re the kind of kid who buys their clothes at Hot Topic". It most often appears alongside Abercrombie & Fitch, Athenian democracy, Athenians.

Reference entry
Hot Topic
Mention count
1
Issue count
1
First seen
February 16, 2022
Last seen
February 16, 2022
February 16, 2022 · Original source
But it’s more than this. It’s an obsession with what kind of person you are. Brand loyalty becomes a way to signal that you’re the kind of kid who buys their clothes at Hot Topic/Abercrombie & Fitch, not at Abercrombie & Fitch / Hot Topic. It’s not that one of these stores is more prestigious (= signals class) better than the other. It’s that they signal what makes you, you. If you shopped just the right combination of brands, you would really capture your uniqueness, and everyone would like you for being you, ie not for boring regressive contigent things like your job or your family (ie your accomplishments and social roles). Result: nobody respects anyone for their accomplishments, nobody wants to fulfill their social roles or do their duties, and everyone wants to be unique and individual = not buy store-brand.
Hot Wheels

Hot Wheels is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "may include Polly Pocket, American Girl, Hot Wheels". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
Hot Wheels
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
Humalog

Humalog is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 27, 2022 and January 27, 2022. The archive places it in contexts such as "Humalog and Novolog are effectively equivalent drugs. They cost ~$300/month without insurance". It most often appears alongside ACA, Acrolectics, Aetna.

Reference entry
Humalog
Mention count
1
Issue count
1
First seen
January 27, 2022
Last seen
January 27, 2022
January 27, 2022 · Original source
The PBM step generally keeps an administrative cost per prescription plus a % of the cost of branded drugs. These companies are: CVS/Caremark, Express Scripts, OptumRx, Prime Therapeutics and a lot of minors. They negotiate "rebates" with manufacturers. This basically works like this: Humalog and Novolog are effectively equivalent drugs. They cost ~$300/month without insurance. The PBM will say to Lilly "That's a nice humalog you've got there. I'm going to need $150/month as a check back to me or else every patient on my plan gets Novolog unless the doctor fills out 500 pages of paperwork to get Humalog AND the patients pay $200 of the cost." Lilly says "ok fine." According to the PBM lobbying organization, PCMA, most of the rebate money goes back to purchasers, but IMO that just makes the problem worse because it makes purchasers complicit in the game by sending them checks that they use to reduce their premiums instead of reducing the cost of drugs to their plan members.
Humira

Humira is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "Humira and Lantus are good examples of drugs"; "Humira and Lantus are good examples of drugs which would be significantly cheaper by now". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Humira
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I would be surprised if Semaglutide was cheaply available as a generic by the mid-2030s unless there are significant reforms made to the patent system or pharma industry rules. Humira and Lantus are good examples of drugs which would be significantly cheaper by now except for repeated patent extension and industry deals maintaining monopolies (although hopefully coming down soon).
Hyundai

Hyundai is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 28, 2023 and September 28, 2023. The archive places it in contexts such as "Hyundai may have solved parallel parking forever". It most often appears alongside 2020 election, @eigenrobot, @jeremychrysler.

Reference entry
Hyundai
Mention count
1
Issue count
1
First seen
September 28, 2023
Last seen
September 28, 2023
September 28, 2023 · Original source
48: Hyundai may have solved parallel parking forever (source):
I SOLVED THE RIDDLE OF THE IDOLS

I SOLVED THE RIDDLE OF THE IDOLS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 30, 2022 and March 30, 2022. The archive places it in contexts such as "gift shop you solved it, he’ll give you 50% off an ‘I SOLVED THE RIDDLE OF THE IDOLS’ t-shirt". It most often appears alongside Comparative Religion, FAANG, Idol Temple LLC.

Mention count
1
Issue count
1
First seen
March 30, 2022
Last seen
March 30, 2022
March 30, 2022 · Original source
“Tell the guy at the gift shop you solved it, he’ll give you 50% off an ‘I SOLVED THE RIDDLE OF THE IDOLS’ t-shirt.”
“Look, go to the gift shop, tell them you solved the riddle, and they’ll give you a 50% off an ‘I SOLVED THE RIDDLE OF THE IDOLS’ t-shirt. Don’t worry, nobody checks to see if you really solved it or not.”
Idahoan

Idahoan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2025 and August 08, 2025. The archive places it in contexts such as "my dad’s currently favored “Buttery Homestyle” Idahoan brand instant mashed potatoes". It most often appears alongside Ainu, Altiplano, American cheese.

Reference entry
Idahoan
Mention count
1
Issue count
1
First seen
August 08, 2025
Last seen
August 08, 2025
August 08, 2025 · Original source
In the interest of full fairness while writing this review, I purchased a plastic cup of my dad’s currently favored “Buttery Homestyle” Idahoan brand instant mashed potatoes for $1.99. The preparation was extraordinarily efficient; the aroma was decent; the taste was a reasonable facsimile; but the texture was all wrong - a smothering paste that coated my mouth and constrained my tongue like a straightjacket. 3/10 would not buy again.
IDOL22

IDOL22 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 30, 2022 and March 30, 2022. The archive places it in contexts such as "give them the discount code IDOL22 for our special deals". It most often appears alongside Comparative Religion, FAANG, I SOLVED THE RIDDLE OF THE IDOLS.

Reference entry
IDOL22
Mention count
1
Issue count
1
First seen
March 30, 2022
Last seen
March 30, 2022
March 30, 2022 · Original source
“I guess you wouldn’t have. But they switch every time anyway.” I pointed to the door. “Gift shop in the back, you can’t miss it, give them the discount code IDOL22 for our special deals.”
iMac

iMac is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 15, 2021 and March 15, 2021. The archive places it in contexts such as "Apple releases new iMacs powered by Apple silicon". It most often appears alongside Apple, Apple silicon, Biden.

Reference entry
iMac
Mention count
1
Issue count
1
First seen
March 15, 2021
Last seen
March 15, 2021
March 15, 2021 · Original source
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races 2. The same party wins both Senate races in Georgia 3. Joe Biden ends the year with his approval rating higher than his disapproval rating 4. Joe Biden ends the year with his approval rating above 50% 5. US GDP growth in 2021 is the fastest of any year of the 21st century 6. The year-end unemployment rate is below 5 percent 7. The year-end unemployment rate is above 4 percent 8. Lakers win the NBA championship 9. Joe Biden ends the year as president 10. Nancy Pelosi sets a definitive retirement schedule 11. A vacancy arises on the Supreme Court 12. The EU ends the year with more confirmed Covid-19 deaths than the US 13. Substack will still be around 14. People will still be writing takes asking if Substack is really sustainable 15. Apple releases new iMacs powered by Apple silicon 16. Apple does not release a new Mac Pro powered by Apple silicon 17. Monthly year-on-year core CPI growth does not go above 2 percent 18. Monthly year-on-year core CPI growth does not go above 3 percent 19. Lloyd Austin not confirmed as Defense Secretary 20. No federal tax increases are enacted 21. Biden administration unilaterally relieves some but not all student debt 22. United States rejoins JCPOA and Iran resumes compliance 23. Israel and Saudi Arabia establish official diplomatic relations 24. US and China reach agreement to lift Trump-era tariffs 25. Slow Boring will exceed 10,000 paid members
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races (60%) 2. The same party wins both Senate races in Georgia (95%) 3. Joe Biden ends the year with his approval rating higher than his disapproval rating (70%) [83%] 4. Joe Biden ends the year with his approval rating above 50% (60%) [60%] 5. US GDP growth in 2021 is the fastest of any year of the 21st century (80%) [84%] 6. The year-end unemployment rate is below 5 percent (80%) 7. The year-end unemployment rate is above 4 percent (80%) 8. Lakers win the NBA championship (25%) [25%] 9. Joe Biden ends the year as president (95%) [96%] 10. Nancy Pelosi sets a definitive retirement schedule (60%) 11. A vacancy arises on the Supreme Court (70%) [50%] 12. The EU ends the year with more confirmed Covid-19 deaths than the US (60%) [80%] 13. Substack will still be around (95%) 14. People will still be writing takes asking if Substack is really sustainable (80%) 15. Apple releases new iMacs powered by Apple silicon (90%) [84%] 16. Apple does not release a new Mac Pro powered by Apple silicon (70%) [53%] 17. Monthly year-on-year core CPI growth does not go above 2 percent (70%) 18. Monthly year-on-year core CPI growth does not go above 3 percent (90%) 19. Lloyd Austin not confirmed as Defense Secretary (60%) 20. No federal tax increases are enacted (95%) 21. Biden administration unilaterally relieves some but not all student debt (80%) 22. United States rejoins JCPOA and Iran resumes compliance (80%) 23. Israel and Saudi Arabia establish official diplomatic relations (70%) [38%] 24. US and China reach agreement to lift Trump-era tariffs (70%) 25. Slow Boring will exceed 10,000 paid members (70%) [75%]
Imagen

Imagen is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 12, 2022 and September 12, 2022. The archive places it in contexts such as "Imagen got 3/5 and so I would say it wins the bet". It most often appears alongside DALL-E2, Gary Marcus, Google.

Reference entry
Imagen
Mention count
1
Issue count
1
First seen
September 12, 2022
Last seen
September 12, 2022
September 12, 2022 · Original source
Google Imagen announced May 2022.
Imagen: 3/5
Imagen got 3/5 and so I would say it wins the bet. There was one snafu, which was that for trust-and-safety reasons, Imagen will not represent the human form (maybe it’s a good Muslim?) We got around this by replacing all humans in the prompts with robots. It still registered surprisingly many trust-and-safety violations for these innocuous prompts, but here’s what we got (slightly edited to always include the best picture of 10):
imatinib

imatinib is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 24, 2024 and April 24, 2024. The archive places it in contexts such as "anti-leukemia drug imatinib". It most often appears alongside 2008 America, @agoodmanbacon, Baicker.

Reference entry
imatinib
Mention count
1
Issue count
1
First seen
April 24, 2024
Last seen
April 24, 2024
April 24, 2024 · Original source
(source) People with cancer are more likely to survive than fifty years ago. This is after you’ve already gotten the cancer, so it’s hard to see how nutrition, sanitation, etc could explain this. Some of these changes (especially prostate) are a result of earlier diagnosis. But others reflect genuinely better treatment. For example, studies have shown great results from the anti-leukemia drug imatinib and the anti-lymphoma drug rituximab. In Robin’s model, these extraordinary studies would have to be bias or chance, and totally coincidentally at the same time somehow better nutrition made leukemia patients (but not uterine cancer patients) twice as likely to survive. Might this be because people are getting cancer younger (and therefore are better able to deal with it?) I can’t find great data on this; there’s increasing cancer among younger people, but (since people are living longer) we should also expect increasing cancer among older people (since there are more older people). Rather than try to figure out how to balance these effects, here’s a graph showing similar survival improvements among childhood cancers in particular, where we wouldn’t expect this to be a problem: (source) Likewise, here is post-heart attack 30-day mortality rate over time: Source here. The odds of death within 30 days of a heart attack have fallen from 20% in 1995 to 12.4% in 2015 (source). This is also no mystery; the improvement comes from increased use of basic drugs like ACEIs, aspirin, and beta-blockers, plus more advanced interventions like thrombolytics and angioplasties, plus logistical improvements like more heart attack patients being placed on specialized cardiac wards. Again, can we dismiss this because maybe heart attack victims are younger? The study this particular graph comes from says their patients were on average 2.7 years older at the end than the beginning, so here age effects seem to point in the opposite direction. Here’s a graph showing the same decline if you break it up by under- and over-65s, though I wish I could find something with smaller bins. Same data for stroke: Source here. Note that these are age-adjusted data! In 2000, a stroke victim is only half as likely to die in the first two years after their illness as they were in 1980. Here we don’t have to worry about age effects at all; the graph is already adjusted for age. You can see similar survival rate increases for other conditions like congestive heart failure (5-year survival rate went from 29% to 60% since 1970), multiple sclerosis (standardized mortality rate went from 3.1 to 0.7 since 1950), type 1 diabetes (survival rate at 50 from about 40% to 80% since 1950) and nearly any other condition you look up. I’m harping on this because it’s in some sense the central example of medicine: you get some deadly disease like cancer, and you want to know if doctors can help you survive or not. All the evidence suggests medicine has gotten much better at this in the past fifty years. Robin’s going to have a lot of hard-to-interpret studies about what happens to your cholesterol score or whatever after you change insurance, and we’ll pick these apart, but to me this seems like a much less central example of “does medicine work?” than the fact that we’re curing cancer and increasing heart attack survival rates. III. RAND Health Insurance Experiment This is considered the canonical study on the effect of health insurance. In the 1970s, RAND gave thousands of people one of five types of insurance, ranging from very bad (barely any coverage until a family reached a deductible of $1000, ie $5000 in today’s dollars) to very good (all care was free). Then they waited eight years. Then they checked whether the people on the good insurance ended up any healthier than the people on the bad insurance. The paper I found measured five questionnaire-based outcomes plus five objective physiological measures, for a total of ten outcomes (Robin says he has a book where they discuss 23 to 30 outcomes, but I don’t have that book, so I’m sticking with the paper). The ten in the paper I read were: Physical functioning questionnaire
Impossible

Impossible is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2023 and March 08, 2023. The archive places it in contexts such as "mix a little cultivated meat with Impossible"; "Impossible or Beyond Meat". It most often appears alongside ACX, Adventist studies, ALLFED.

Reference entry
Impossible
Mention count
1
Issue count
1
First seen
March 08, 2023
Last seen
March 08, 2023
March 08, 2023 · Original source
Is Cultivated Meat For Real?, by Robert Yaman. I’d heard claims that cultivated (eg vat-grown, animal-cruelty-free) meat will be in stores later this year, and also claims that it’s economically impossible. Which are true? This article says that we’re very far away from cultivated meat that can compete with normal meat on price. But probably you can mix a little cultivated meat with Impossible or Beyond Meat and get something less expensive than the former and tastier than the latter, and applications like these might be enough to support cultivated meat companies until they can solve their technical obstacles.
Impossible Burgers

Impossible Burgers is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 26, 2021 and February 26, 2021. The archive places it in contexts such as "you’ve probably tried Impossible Burgers". It most often appears alongside American Chinese food, Bay Area, BBQ pork rice.

Reference entry
Impossible Burgers
Mention count
1
Issue count
1
First seen
February 26, 2021
Last seen
February 26, 2021
February 26, 2021 · Original source
By this point you’ve probably tried Impossible Burgers, and you know that restaurants can do some pretty impressive things with them. But there are so many interesting meat dishes - what if you want something other than a burger? This market is still developing, but I live in the Bay Area, which is probably its epicenter. And I’m mostly-vegetarian, so I have no choice but to try it out.
If you’ve had Impossible Burgers and are looking for something more interesting, my favorite dish from this round of reviews was the chicken at Nature Vegetarian Restaurant. General Tao’s and Salt & Pepper were especially good.
Impossible Meat

Impossible Meat is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 26, 2021 and February 26, 2021. The archive places it in contexts such as "Impossible meat is good, but Crave is the first restaurant I've seen to incorporate it into a sub"; "this is the only local restaurant I've found that takes the potential of Impossible Meat seriously". It most often appears alongside American Chinese food, Bay Area, BBQ pork rice.

Reference entry
Impossible Meat
Mention count
1
Issue count
1
First seen
February 26, 2021
Last seen
February 26, 2021
February 26, 2021 · Original source
The burrito was terrible. The meat had some kind of weird flavor to it, I don't know if it was the taste of whatever meat substitute they used, something they added to disguise the taste of the meat substitute they used, or a real Mexican sauce gone horribly wrong. If they had Impossible Meat, I don't know why they didn't just use that (I mean, I guess they didn't have Impossible Meat, but...) The fries were terrible in the same way as all delivery fries, plus a little extra.
Crave's Kim Possible was also great. It's no longer really surprising that Impossible meat is good, but Crave is the first restaurant I've seen to incorporate it into a sub, they've beaten Ike's to this milestone, and they deserve credit for this.
I give Ike's 4/5 stars and Crave 3/5, though it's hard for me to decide how to award points for Crave having Impossible Meat and Ike's not having it. If you haven't tried plant-based meat sandwiches, you'll probably be impressed by either of these places.
Indic Bricks

Indic Bricks is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 29, 2024 and February 29, 2024. The archive places it in contexts such as "Hinduism has Indic Bricks". It most often appears alongside @BoyanSlat, @eigenrobot, @JackTindale.

Reference entry
Indic Bricks
Mention count
1
Issue count
1
First seen
February 29, 2024
Last seen
February 29, 2024
February 29, 2024 · Original source
26: Did you know: lots of religions have their own version of LEGO, usually with sets depicting their mythology or temples. Islam has Muslim Blocks, Hinduism has Indic Bricks, and Judaism has Binyan Blocks. But my favorite is Mormonism with - wait for it - Brick’em Young (h/t @seanw_m)
InstructGPT

InstructGPT is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 10, 2022 and June 10, 2022. The archive places it in contexts such as "maybe (but maybe not, see footnote 1) true that InstructGPT is genuinely better than GPT-3". It most often appears alongside 4chan, Alexander the Great, Caesar.

Reference entry
InstructGPT
Mention count
1
Issue count
1
First seen
June 10, 2022
Last seen
June 10, 2022
June 10, 2022 · Original source
Now it is true that GPT-3 is genuinely better than GPT-2, and maybe (but maybe not, see footnote 1) true that InstructGPT is genuinely better than GPT-3. I do think that for any given example, the probability of a correct answer has gone up. [Scott] is quite right about that, at least for GPT-2 to GPT-3.
Intel

Intel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 07, 2024 and May 07, 2024. The archive places it in contexts such as "people fleeing Intel ... but that Intel had 'gone woke' in its hiring / promotion". It most often appears alongside affirmative action, Africa, African National Congress.

Reference entry
Intel
Mention count
1
Issue count
1
First seen
May 07, 2024
Last seen
May 07, 2024
May 07, 2024 · Original source
5) Yes I didn’t talk about the origins of inequality. That would have been a bad strategy. I prefer what Scott calls the “meta-honesty” approach, where you tell people exactly what you’re not going to talk about and why. This means that the pieces are all there for an intelligent reader to figure out what you think, while making things hard for the cancellers and political opponents. This is a political book, and I sometimes do politics, which I justify with the meta-honesty approach. Scott has a revulsion towards this, which I consider having the flaw of being too pure for this world. I, in contrast, have an appreciation for politics as an art, and this is maybe just an aesthetic thing. But I will never lie to or mislead you about what I think, and believe others should live up to the same standard, even if they sometimes practice selective silence.
I heard (at Samsung, from people fleeing Intel) that Samsung was still meritocratic in this way / the nepotism was all pro-Korean nationals in a way that totally ignored American racial categories, but that Intel had 'gone woke' in its hiring / promotion.
This DEFINITELY happens with the parts of the federal bureaucracy that I am involved with. I have daily contact with federal bureaucrats, and the recent hires/promotions are wildly more "diverse" (out of all proportion with the population honestly), and of very poor quality. So you have a lot of 55-65 year old white male civil servants of very high ability and intelligence, being replaced by pretty low capacity 30-40 year old minority women of startlingly poor intelligence and ability. On paper they have similar credentials, but they are not similar caliber people. In general obviously, there are exceptions in both cases. The preference HR policies clearly have *something* to do with it.
Intellicare

Intellicare is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Intellicare is a series of CBT apps". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
Intellicare
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Intellicare is a series of CBT apps; you can download it for free as “Intellicare Hub” here or on the Google or Apple stores. I have never tried it, but the Carlat Report says nice things about it, and it has several successful studies under its belt.
Intralipid

Intralipid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 06, 2021 and August 06, 2021. The archive places it in contexts such as "The US standard is a nutrient fluid called Intralipid, which uses soybean oil as its main fat". It most often appears alongside American College of Clinical Pharmacy, ASPEN, BCH.

Reference entry
Intralipid
Mention count
1
Issue count
1
First seen
August 06, 2021
Last seen
August 06, 2021
August 06, 2021 · Original source
Omegaven is a fluid for parenteral nutrition. If your digestive tract doesn’t work (a problem frequently associated with newborn babies), then you risk starving to death. Doctors can avert this by pumping nutrients directly into your veins through an IV. This is notoriously hard, because food has lots of nutrients, and if you try to put together a complete replacement for food you will probably miss something. The US standard is a nutrient fluid called Intralipid, which uses soybean oil as its main fat. Because of the usual random cross-national differences in medicine, Europe used a formulation with fish oil as the main fat (though I’m not sure whether they used it along with soybean or on its own). In the early 2000s, nobody thought there was any interesting difference between these.
Intuit

Intuit is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 11, 2021 and December 11, 2021. The archive places it in contexts such as "to the delight of Intuit". It most often appears alongside /r/georgism, ACX community, Aggregate Land Rents, Expenditure on Public Goods, and Optimal City Size.

Reference entry
Intuit
Mention count
1
Issue count
1
First seen
December 11, 2021
Last seen
December 11, 2021
December 11, 2021 · Original source
Gwartney says that when he was the assessment commissioner and chief executive officer in British Columbia, he had a staff of 690, and that this number has not changed significantly since then. British Columbia has a population of about 5 million, so that's 1 assessment officer for every 7,250 British Columbians. For context, the IRS has a staff size of 74,454, or about one IRS agent for every 4,425 Americans. I don't have data on how many property tax assessors the USA has in total, but the above slide suggests British Columbia's figure is on the high end. As for how you actually do assessments, sure, you can send out an army of assessors to value each and every property in your jurisdiction by hand. However, not only is that labor-intensive, it's also a recipe for inconsistency. Whatever method you're using to value properties needs to be consistent and standardized across all properties, so you don't have sharp discontinuities on the assessment map that are due solely to differences between Assessor Fred and Assessor Sally's personal methodologies. Thankfully, we're living in the modern age, and we have some fancy new tools at our disposal. 4. Modern Technology Georgists were doing split-rate assessments to allegedly good success long before the rise of the computer, such as J. J. Pastoriza's effort in setting up a Georgist tax regime in Houston, Texas in 1911. Today, we have spreadsheets, property value databases, GIS mapping visualizations, regression analysis, machine learning...the works. According to Gwartney, the Canadian province of British Columbia has revalued all its land and all its property on an annual basis simply by using computers and market analysis, ever since he first helped them set up their system back in 1975. Not every jurisdiction revalues their land this thoroughly and this often, but Gwartney says there is no significant technical or staffing barrier standing in the way. Gwartney has been retired for some time, so his seminar didn't cover all the latest cutting-edge techniques that have come out in the last few years. Let's look at some recent papers and see what new tools assessors have to play with. The first on my list is Land Value Appraisal Using Statistical Methods by Kolbe, Schulz, Wersing, and Werwatz (2019). This is a study on mass appraisal techniques using real estate transaction data from Berlin, Germany. It claims that not only are the results cheaper and faster to generate than those done by conventional property assessment methods, but they are also no less accurate than those done "by hand" by experts. Kolbe et al. assert that, provided you have access to high quality market transaction data, you can perform accurate and efficient mass appraisals of land values. They chose Berlin because it "has a very effective system of property transaction data collection and storage," in contrast to other parts of Germany. They cite some prior work by Almy (2014) studying Canada, the Netherlands, and the United States, suggesting that the assessment cost per property can be brought down to 20 Euros–25 times cheaper than what some other people (Fuest, et al. (2018)) assert. Given an average tax receipt of 2,000 Euros per property, this means that the assessment cost should represent only about 1% of the funds raised. Is that good? Let's take this assertion at face value for the moment and compare it to the cost of the IRS. Federal tax receipts in 2020 were $3.42 trillion, and operation costs for the IRS were $12.3 billion, or 0.36%. However, the IRS outsources most of the labor of tax preparation to the taxpayers themselves, with compliance costs estimated between $200 billion and $400 billion a year, to the delight of Intuit. Add that up and the total cost of federal tax collection to the economy is anywhere between 6-12% of the amount it raises. And what about sales tax? According to a 2006 report by PriceWaterHouseCoopers: The study finds that the national average annual state and local retail sales tax compliance cost in 2003 was 3.09 percent of sales tax collected for all retailers, 13.47 percent for small retailers, 5.20 percent for medium retailers, and 2.17 percent for large retailers So a compliance cost of 1% would be way more efficient in terms of cost collection than the other two most common forms of taxation, and taxpayers don't even have to do anything themselves, other than pay the bill. Alrighty, how about the accuracy? The authors cite two international examples, Australia and Lithuania, as among the few countries in the world that have both a Land Value Tax and statistical methods for mass appraisals. Hefferan and Boyd (2010) assert that objections to assessments from property owners in Australia are less than 1%. I'm willing to buy the improved efficiency claims just by taking a look at some methodologies. It seems reasonable that computerized records and algorithms can cut costs significantly; the real question is if you're trading off accuracy. The other papers I found on the subject are Bencure, et al (2019) in BayBay City, Philippines, Kilić, et al (2019) in Croatia, Yalpir & Unel (2017) in Konya, Turkey, and Raslanas et al. (2014) in Vilnius, Lithuania. Let's dive in and examine some methods. 5. Mass Appraisal Methods Here are some of the latest mass appraisal methods cribbed from the research papers listed above. All of these are based on taking market transaction data, plotting them out on a map, and running computations over them to estimate valuations for the properties you don't have known values for. Furthermore, all of these methods are able to value land and building values separately. Multiple Regression Analysis This paper by Yalpir and Unel out of Turkey gives a straightforward example of using Multiple Regression Analysis for land valuation. For those of you who didn't study math, let me explain regression analysis. This is a family of mathematical models where you basically take a data set, ask the question "what mathematical formula would best fit this data," choose a basic equation model, and then have a computer search for a set of coefficients that "best fit" that curve to the data with the least amount of error. The simplest example is using linear regression on a scatterplot of observed data points to fit a trend line. This is a common exercise in freshman physics and statistics classes. You can use more complicated versions of this numerical method to take a big bag of observations (real estate sales) and use "multiple regression" to tease out dependent variables (land value and improvements value) based on the independent variables (size, location, age, number of bedrooms) of your observations. In this case the team identified about a hundred different factors that can affect the price of a property: Then you create an entry for each property, fill in the values for each of those characteristics, and run it through the regressor. Take note of how many of these factors start with the words "proximity to." Each of these can be calculated automatically just by knowing where the property is on a map, and each of them is an independent contributor to the value of the property's location. The next step is to generate individual "index maps" that combine various related features into combined heat maps. Then you run everything through and see if it works. You can get the land share of the final value by combining the contributions of all the individual factors that you associate with "land," such as proximity to important things. In the verification section the authors say: As a result of the analysis, since the significance level (0.000) p <.05, corresponding to the F values in the ANOVA test, indicates that the regression analysis is appropriate and the models are significant. The criteria that make up the model account for about 85% of the market value and 15% cannot be explained for reasons such as economic, non-existent data and unearned income. Unfortunately, they don't say anything about how accurate their model is for assessing land values specifically. Otherwise, this is a pretty good example of using the Multiple Regression method for estimating the individual contributions of various factors to overall property values. Gwartney says Multiple Regression Analysis was a standard method he typically used, of which this specific paper is just one example. Nonparametric kernel regression This will be a method familiar to the programmers in the audience who have any experience with image processing algorithms. Here's an example from this old Gamasutra article: The basic idea here is to take a matrix of numbers, called a "kernel", and run that over every pixel in a source image. The kernel tells you how strongly to weight all of the source pixel's neighbors to compute a final result for that position. A simple "box blur" is a kernel where every value is 1 (meaning it averages the values of all neighboring pixels within a range). The more subtle gaussian blur illustrated above uses a two-dimensional normal distribution of values so that each pixel is most affected by those nearest to it. So let's apply the same principle to land valuations. If you have a map with lots of transaction data of pure land sales–defined as sales of either vacant land or teardown properties (where the building value is essentially zero)–then you can use a special kernel filter to smoothly interpolate land values across the region. So you basically have a smooth curve that mostly favors close-by points, tapers off a bit, and then disregards anything outside a certain distance entirely. The big assumption here is that land values change smoothly and do not change suddenly across very short distances. There are, in fact, locations with sharp jumps in value (any town with an "other side of the tracks," for instance). But for cases where we know a priori that land values change smoothly, this method is appropriate. No other prior restriction is placed on the form of the land value map, however, and this is why it's called "nonparametric." Here's an illustration. The outer box is the entire search distance that the kernel considers, and the circles represent the falloff of the curve itself. The size of the box is called the "bandwidth" and is set by the user. Everything outside of it will have zero influence on the kernel's output at any given location. This method operates on the same basic logic that I used when I hand-estimated the land value of that San Francisco house in Part I based on the value of the empty lot next door. However, it makes the whole procedure systematic. It can easily and accurately estimate the land value of a property with a big fat building on it simply by smoothly interpolating the known values of the nearby parking lots. Of course, it has limitations. First and foremost, it's a highly local operation, so if you have properties you're trying to value that don't have nearby pure land sales data, you can't really do much with this. Also, most people assume that city centers have less market transactions for undeveloped land than the countryside, as did I until I read that paper by Albouy in Part I. But in any case, this is just one method in your toolbox and might not be sufficient by itself. Its key advantage is that it works directly from true market data for land and doesn't need or want any other subjective data. In the end, basic kernel estimation just fills in the land value of unmeasured locations with a local weighted average of known locations. Nonparametric adaptive regression Kolbe, et al. build on the kernel regression method with a technique called Adaptive Weights Smoothing (AWS), which runs in several iterations and adds additional weight to any observed data points that are sufficiently close to the point being estimated. I'm not 100% sure about what all the math means, but it seems like it's basically a "smarter" version of the basic kernel method. Left: Nonparametric kernel regression, Right: Adaptive Weights Smoothing. I think the authors goofed and printed the same figure twice with different headings because they're identical if you overlay them in Photoshop. Semiparametric regression Now, the above two methods assume you have plenty of "pure" land sale records to work with. But if you're trying to work out prices in the city center, you've probably mostly got land and buildings mixed together. To do this effectively, we need more data, and this is where the "parameter" in "semiparametric" comes in. The model described in Kolbe et al. seems like a flavor of multiple regression analysis that takes the price, the location, and various characteristics of the building and feeds it into a regressor. But we've got "semi" parametric here. What does that mean? Well, if you already know how certain relationships between the data work a priori, it's better to enforce those relationships yourself rather than leave it to the computer. Here, we enforce the assumption that if two properties are right next to each other, then the value due to location is going to be essentially identical. This algorithm starts by ordering things geographically and then working out the differences in observed price by regressing on the difference between remaining property characteristics. In this method, the power of "location, location, location" is not something we're leaving to the regressor to discover by itself. Results of the Semiparametric regression method, we can see some significant differences from the simple kernel-based model. As you can see above, this gives you more detailed and likely more accurate results, and you're better able to assess the values of properties with buildings on them, even in the absence of pure land sales. This technique is more complicated and bakes in assumptions about the power of location, but otherwise doesn't assign subjective human weights to the various property characteristics. The chief human bias comes in the form of deciding which property characteristics are measured and made legible to the model in the first place. Okay great, but how accurate are the above three methods? Their main point of comparison is this thing called the "Bodenrichtwerte," or BRW. I think that means "ground-level-values" in English, and it's an expert-assessed map of land values for Berlin done the traditional way. The nonparametric kernel regression method has a correlation of 0.704 with the traditional method and has the added disadvantage that it's not able to produce estimates for the city center, only the outlying areas. Furthermore, the BRW map does show sharp discontinuities, which is another knock against the kernel method, at least for the city center. What about the iterative method? Kolbe et al. find that "the agreement between [Adaptive Weights Smoothing] land value estimates and, both, land prices and BRW land values is fairly good for all values of λ." Doing some quick checks, their values seem to be within about 85% of the BRW values. A different Kolbe et al. paper called Identifying Berlin's land value map using adaptive weights smoothing goes into more detail and claims to give "similar" values to that of the BRW. For the semiparametric method, they "found a strong positive correlation of 0.845" between their numbers and a previously expert-assessed set done using the traditional method. That sounds pretty good. It seems their margin for error is about plus or minus 15% compared to the traditional expert method. I'd like to see more direct comparisons against market transactions themselves, though, because if the prior expert assessments are wrong, then the main achievement here is improved efficiency, not accuracy. However, this method doesn't seem to be dramatically less accurate than the old way of doing things. The last three models came from the Berlin case study, where you have excellent market transaction data in an extremely wealthy and high-trust society. But what if you're trying to assess land in a developing nation with poor market transaction records, weak institutions, and widespread poverty? Innovative Land Valuation Model (iLVM) This is the particular name of the method described in Development of an Innovative Land Valuation Model (iLVM) for Mass Appraisal Application in Sub-Urban Areas Using AHP: An Integration of Theoretical and Practical Approaches by Bencure, Tripathi, Miyazaki, Ninsawat, and Kim. They used BayBay City, Philippines as their case study. Whereas the previous models are very "hands-off" and let the computer work out the relationships between prices and property characteristics, here you get expert human opinion directly involved in building the model, baking in weights that directly embody judgments like "properties next to major roads are more valuable." These judgments are based on expert opinions that presumably come from observed experience but are a priori judgments nonetheless. Here, look at this big complicated flowchart. The "Analytic Hierarchy Process" in the box on the left is a particular kind of method for getting experts to set weights. The authors give this reason for using it: Despite criticism pinpointed by other scholars, the AHP remains the commonly used in many research fields and practical applications. This is because the AHP: (1) overcomes human difficulty in making simultaneous judgment among factors to be considered in the model; (2) is relatively simple as compared to other MCDA [multi-criteria decision analysis] methods; (3) is flexible to be integrated in various techniques such as programming, fuzzy logic, etc.; and (4) has the ability to check consistency in judgment After identifying a list of "factors" that can affect land value, they group them into taxonomical buckets: Note that certain factors like "Coastline" appear in multiple buckets; this captures the various influences a characteristic can have. For instance, land on the coast tends to be more economically valuable because of tourism, shipping, fishing, etc., so that goes under "economic." But land that's next to the coast is also more likely to flood, so it also goes under "environmental." And then there are various land use restrictions that apply specifically to coastal areas, so it goes under "legal" as well. In this way, a single factor like "the property is on the coastline" can have both positive and negative effects on land value (e.g., it's more economically valuable but it also might flood, and there are certain things you aren't allowed to do there). The next step is to set down some rules for how sensitive each factor is to location and distance. So here we can see that the economic benefit of being on the coast is most strongly felt if you're within half a kilometer of the ocean, but the environmental effect (e.g., risk of flooding) is most strongly felt when you're within 0.03 kilometers. And so on and so forth. Your experts help you work out all these rules. Note that for a few of these factors (such as land use and slope), you use metrics other than distance (e.g. land use classification and grade). Then you take all that stuff and assign everything a value between 0 and 5. Your team of experts then uses this table to come up with a set of weights for everything. What essentially comes out of this is a big linear equation with a bunch of coefficients for every one of your factors, which is then broadly fit to the observed market prices. When you're done, you can take any property on your list, multiply each of its characteristics by its respective weight, run that through your equation, and calculate the predicted price of the land. So how accurate is it? The authors compare it to standard Multiple Regression Analysis and claim it fares better. The Root Mean Square Error is quite a bit less than MRA. In addition, I think it's also saying that the MRA algorithm decided that only four of the factors were significant and basically ignored all the rest. By contrast, iLVM was able to maintain contributions from all the factors, because it doesn't leave that decision to the computer. I'm not 100% sure; it's not clear from the paper. The authors claim that about 67% of the variability is explained by their model, but they note that there are some areas where the model can be off by more than a factor of 1.0 in either the positive or negative direction. One thing that's kind of fun about this model is that you can make neat graphs like this that show the individual contribution of each factor: The main downside to this model is that it relies on a whole lot of subjective expert opinion and can be questioned on that basis. That said, it can be cheaply deployed in a transparent and consistent way across a large area. You can see why that's attractive for a developing nation with weak institutions and poor market transaction records; the argument is that this is a significant improvement over the former status quo. I wonder how well this model performs when you feed it better market transaction data, and how that would compare against all the others methods under identical conditions. More research is needed. Rather than drag you through a bunch more research papers, I'll just leave these others I found cited in the above studies: Killić et al. (2019) - Fuzzy expert system for land valuation in land consolidation processes
Invega Trinza

Invega Trinza is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 18, 2024 and July 18, 2024. The archive places it in contexts such as "technically Invega Trinza promises every three months". It most often appears alongside Access Pass, Africa, America.

Reference entry
Invega Trinza
Mention count
1
Issue count
1
First seen
July 18, 2024
Last seen
July 18, 2024
July 18, 2024 · Original source
I’ll just add a couple of things. First, I’m not surprised that Merlot hasn’t seen “every few months” because that’s still kind of cutting-edge and might not have made it to Canada, but technically Invega Trinza promises every three months. It’s still very expensive (something like $10,000 per dose), so any health system with resource constraints is probably using older monthly ones that cost a few hundred per dose.
Invokana

Invokana is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "Janssen's Invokana diabetics drug has also been proven to cause weight loss". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Invokana
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
As an interesting aside, Janssen's Invokana diabetics drug has also been proven to cause weight loss. https://www.fiercepharma.com/pharma/proof-concept-trial-j-j-s-invokana-combo-helps-non-diabetics-shed-significant-weight sadly the trials went nowhere after in 2017 invokana got slapped with a black box warning for heightened risk of big toe amputations. A risk that one may be willing to take to treat diabetes but not weight problems. There must be something in mechanism of action of diabetes drugs that causes this nice weight loss side effect.
iPad

iPad is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 03, 2023 and April 03, 2023. The archive places it in contexts such as "2 years before the first iPad". It most often appears alongside 2008 Act, ACX, Adderall.

Reference entry
iPad
Mention count
1
Issue count
1
First seen
April 03, 2023
Last seen
April 03, 2023
April 03, 2023 · Original source
If for some reason that doesn’t work, go to a different psychiatrist and try again. You don’t have to tell them you already tried. Since everything about ADHD diagnosis and treatment is already security theater, it’s hard to say what pill mills are doing except kind of smirking under their breath while going through the rituals - as opposed to real doctors, who go through the rituals with sincere faith. Don’t get me wrong, I do think there’s a difference here. But the regulatory state isn’t set up to say “And you have to sincerely believe in the rituals or they don’t count”. So instead they punish unrelated groups, like telepsychiatrists. See also my old post Bureaucracy As Active Ingredient. The security theater doesn’t work because it’s effective. It works because it’s inconvenient enough to weed out the less motivated fakers, and some of the remaining fakers get cold feet about lying to a nice sincere psychiatrist who seems to be trying to help them. Pill mills remove the inconvenience, and seem to be nod-and-wink cooperating with liars, so the theater stops working. The only solution is to inject some inconvenience and shame back into the process somewhere, which the DEA has chosen to do by restricting telepsychiatry. They could accomplish the same goal by making you attend your appointments naked, but I guess clothing companies have better lobbyists than telepsychiatrists do. 4: Comments About Forcing Blind People To Fill Out Forms Before They Can Access Braille I analogized forcing patients to see an in-person doctor before they could access a teledoctor to forcing blind people to fill out forms before they could access Braille. Several blind people and their friends pitched in to say this was a real problem. For example, Mikolysz: Blind person here, this kind of thing is actually much more common than people imagine. Many government agencies (regardless of which particular government you mean) just assume that anybody who needs to fill a form can read and write print and/or lives with somebody who does. This is often a problem even when the form in question is specifically targeted at blind people. Non-governmental organizations, including those who specifically serve the blind, aren't much better at this either. This issue is slightly more pronounced in civil law countries, where what constitutes a legally-binding signature is clearly defined in law and you can't just Docusign your way out of the problem, but it exists everywhere, including the US. I literally had to file this kind of document today, while the main form could be filled electronically, I was required to attach a few extra documents, for GDPR and such, and those had to be printed, filled in by a sighted person, signed and scanned. The same problem exists with physical mail which you're required to read and respond to, but which is almost never available in an accessible form, a few exceptions like the American IRS notwithstanding. 5: Comments About My Caricature Of A Doctor Who Refuses To Prescribe Psych Drugs Because People Just Need Jesus Jon Cutchins writes: You don't want psychiatrists and liberals in general to be accused of an unreasoning hatred towards Christianity you should probably be more judicious in your use of anti-Christian tropes when describing everyone who is skeptical of mind-altering drugs. Mike writes: I’ve been a primary care nurse practitioner in the Bible Belt for 20yrs and not once have I even heard of a provider telling a patient they should substitute religion for psychiatric (or any) medication. It’s so easy for some people to throw around these tropes as if Christianity is some exotic, weird tribe with horrifying anthropological traits. On the other hand, fluxe writes: I am a young Christian--in my life, I have -been told by my PCP not to get an IUD because it carries "a significant risk of causing infertility or death" -had a pharmacist refuse to fill an old, male family friend's ulcer medication because it's also an abortifacient -been told by a therapist to discontinue the SSRI a different provider had prescribed and just trust in the man of the house the PCP wasn't even particularly Christian herself, but since all of her patients are she hadn't updated on IUDs since the scare back in the 70s. Our horrifying anthropological traits become everyone's problem--it might be worth listening to those who "throw around these tropes" so you can understand what they have to deal with Unfortunately I only mention this possibility because it’s happened to several of my patients. The best I can offer in terms of being unbiased and apolitical is to signal-boost posts like this one about overly woke therapists being another big problem. Alien on Earth writes: I generally like your writing and ideas, hell, I just re-uped for a year. However, in an otherwise near perfect post, you took a cheap shot at a steriotyped view of one religion thst is not popular amoungst coastal elites, that really detracts from your core point. "The worst-case is that you get one of those doctors who think that Psych Drugs Aren’t Real Because You Just Need Jesus, and then the patient has to keep looking until they find someone else." In my experience, it is the new age(y), non-religious, doctors who are least likely to like prescribing psyc. meds or who tend to give them at too low a dose or for too short a time. Certainly, I've found little correlation with their religion, if I even know it. The only correlation I've observed is that this perscription reluctance is, perhaps, slightly more common amongst middle career doctors. Perhaps it is more common in deep red areas, I don't know. However, even there, I would suggest, it is less due to religion, per se, than to "old fashion" "grit your teeth and bear it" thinking. I agree that there are many reasons people recommend against psychiatric drugs (a few are even good). Psychiatric drugs have lots of side effects and are clearly imperfect options, and I see people object to them more often when they think they have a perfect option as an alternative. Sometimes that option is Jesus. Other times it’s the trendy new somatic yoga reprocessing kundalini trauma dianetics therapy. Other times it’s LSD or ketamine or Dr. Bob’s 24-In-One Internet Nootropic. All of these work for some people, but not as much as the people pushing them think - which I guess is also true for psych drugs. I’m nervous about people who think they’ve found the answer and pressure people towards one alternative or another without presenting evidence. I’ve seen this happen enough in religious contexts that I think it was a fair thing to use as an example. 6: Comments About Which Part Of The Government Is Responsible For This Regulation ProfessorE writes: I’m not sure that what Scott wrote is even completely accurate. I have a relative who is an MD in this space, and it seems that the underlying problem is not the DEA but an actual law passed by Congress. Aren’t telemedicine regulations limited with respect to controlled substances by the Ryan Haight Act of 2008 U.S.C. § 829(e)… there may be interpretations of this act by the DEA and other agencies, but, where controlled substances are prescribed by means of the Internet, the general requirement is that the prescribing Practitioner must have conducted at least one in-person medical evaluation of the patient. It seems like a colossal overreach to ask an Executive Branch agency to overrule the plain text of the act. There are some exceptions, which Scott noted. A different way of looking at things was that the Executive Branch was highly responsive to the emergency situation of Covid. Now that it’s not an emergency, they are obligated to return to the legal framework that exists. Congress needs to change the law, not the DEA. The *data* from covid should be used as part of a cost-benefit analysis to determine whether it is reasonable to regulate telemedicine, and, if so, what regulations might address whatever problems arose. Followed by: Actually, Scott is even more off-base than I thought in my initial post. Apparently the DEA & DOJ are already proposing new changes to the 2008 Act (which seem like they violate the clear text of the act), but the act and the changes are summarized here: https://www.legitscript.com/2023/03/27/proposed-changes-ryan-haight/ Sounds like government is aware of the issue. See https://www.federalregister.gov/documents/2023/03/01/2023-04248/telemedicine-prescribing-of-controlled-substances-when-the-practitioner-and-the-patient-have-not-had For the actual changes that are being proposed. End of the day, this should be modified by Congress, not the agencies. Everyone should remember that the law was written in 2008. That’s 1 year after the very first iPhone and 2 years before the first iPad. Zoom didn’t exist (2011). None of the other technologies for video conferencing existed. Congress was attempting to fight opioid pill-mills. At the time of passage, I am willing to bet that ≈0% of patients were “Telehealth” using videoconferencing. More like phone calls and email a few times to get drugs. The law should have been amended, and it hasn’t been, but it is far from clear that it was a crazy law in the first place. I mostly accept this correction, although I’m still a bit confused - a lot of the analyses by lawyers I read said things like “Unquestionably, the DEA’s proposal is not what most industry stakeholders were anticipating. The initial reaction is the rules are more restrictive than necessary and impose concerning limitations and burdens on clinicians and the patients they treat”, and I’m confused why industry stakeholders weren’t anticipating it if the DEA had to do it in order to follow the law. And JR writes: Meanwhile, the DEA was instructed by law in -2008- to develop a special registration process for telemedicine to allow providers to prescribe controlled substances remotely. The DEA has simply failed to do so in that time, despite repeated Congressional demands to act. Don't worry, though - the DEA has said about this proposed rule that it feels this will be 'less burdensome' for providers than any kind of special registration, so it feels it has discharged its legal responsibility to create a special registration process. I am a psychiatrist having to deal with this idiocy with my patients too, and renting an office temporarily is not going to cut it. So I am going the letter route. I will probably a lose a reasonable chunk of patients I was prescribing controlled substances to. The only possible saving grace is that PCPs in this country are used to being asked to sign and complete all kinds of nonsense forms and documents so probably most of them will just do it with minimal fuss. I'm more concerned with the new requirement that all telemedicine scripts now have to be recorded by the prescriber with the date and time they were written, the PHYSICAL ADDRESS of the prescriber and patient at the time of the telehealth encounter, and have an explicit note on them that they are telemedicine prescriptions. I am less concerned about PCPs balking at writing an idiotic referral than I am skittish pharmacists refusing to fill scripts that they might interpret as being labeled equivalently to FAKE SCRIPT FOR DRUGSEEKERS Based on that comment and this, my best guess about what’s happening is: Congress passed restrictions on telemedicine in 2001, and asked the DEA to come up with a way that trusted providers could avoid those restrictions. Now that there is videoconferencing, etc, most people now believe those restrictions were too severe.
iPhones

iPhones is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 21, 2021 and May 21, 2021. The archive places it in contexts such as "savings that can be used for whatever Americans (or their government) want, from iPhones". It most often appears alongside 1992 treaty, ACX, Africa.

Reference entry
iPhones
Mention count
1
Issue count
1
First seen
May 21, 2021
Last seen
May 21, 2021
May 21, 2021 · Original source
We didn’t just get tremendous economic growth though – we got “magical” results, but they were based on a one-time confluence of factors that “overwhelmed the normal rule that lots of twenty-and thirty-somethings make for an expensive-capital environment.” What were these one-time accelerants? He identifies the peace dividend – cuts in military spending that allowed capital to be put to more productive uses – as one such change, along with the emergent dominance of the US dollar, particularly boosted by Russian demand thanks to the collapse of their currency, and a later boost in demand thanks to the East Asian financial crisis. With the Europeans’ decision to eliminate national currencies (agreed upon in a 1992 treaty, with the Euro to be introduced in 1999), they became relatively unattractive, and the Euro itself (an “unprecedented experiment in pan-government planning”) was too risky. Many holders of European currencies switched to the US dollar, such that between 1994 and 2002 (“when the euro finally got some traction and the surge dialed back”) there was a $2 trillion increase in the money supply. Zeihan also points to a collapse in commodities prices influenced by the elimination of Russian demand, but continued Russian production of oil and other commodities, followed by a collapse in demand thanks to the East Asian financial crisis. This story of capital coming to the West (“allowing consumption-driven growth not simply to soar, but to explode”) is one of chance world events. However, the story of capital coming from the Boomer cohort is one of demographics. By the 2000s, they’re the mature workers of Zeihan’s four stages described above – and as the bulge in the demographic pyramid, they started flooding the world with capital. Accordingly, “The cost of credit plummeted to levels never before experienced.” Zeihan suggests that developed-world demographics are the cause of booms in places that haven’t been well-developed, from Southern Europe to Brazil, Russia, and India. But he says it’s quickly coming to an end; Boomer savings into stocks and bonds will be moving to low-risk instruments and then turning into withdrawals rather than savings, and the cohort behind them is too small to replace all of that capital. And it’s a worldwide phenomenon: In every single developed country there is currently an American-style population inversion between the about-to-retire and the about-to-be-mature-workers age groups. Japan’s Boomers bulge is a decade older than the American equivalent, while Spain’s is roughly fifteen years younger. Everyone else falls somewhere in between. It dictates a period of chronically low growth and high credit costs, just not on precisely the same time frame. The undeveloped world is that way because it can’t self-fund, so without foreign capital, their growth will come to an end. In sum, the 1990-2005 period of high growth and easy capital was a historical anomaly; “the post-Cold War financial flight was a once-in-a-generation event” and the demographic bulge that coincided with it won’t come around again for decades, if ever. 4 2: America’s incredible advantages As noted above, Zeihan really likes America’s position in the world. He likes its demographics (relative to other developed countries) and loves its geography. Taking the population question first, in America, “the demographic inversion is only a temporary development.” America is younger than the rest of the developed world, as it urbanized later and its enormous size made having kids easier despite that urbanization (i.e., the suburbs exist). This makes the demographic crunch a single-generation issue, as the Millennials are a huge cohort. And even if they weren’t, America assimilates immigrants more easily than other places – Zeihan attributes this to it being a “settler society” – which can help with demographic problems. The rest of the developed world doesn’t have similar cohorts following their massive Boomer and Gen-X analogues. Accordingly: While the American financial world will be past its period of maximum stress by 2030, for the rest of the world 2030 will simply be another year of an ever-deepening imbalance between retirees and taxpayers, with smaller and smaller generations coming up the ranks generating less and less growth. For the developed world beyond the United States—and even large portions of the developing world—chronic capital poverty and permanent recession will be the new normal from which there is no return. Together with America’s Millennial-led growth and abundant energy (there’s a chapter explaining how shale is a done deal that, as of the mid-2014 writing, already made America the world’s largest energy producer 5), by 2030 Zeihan sees it as practically the only country with an economy worth noting. Anyone who is familiar with American geography should see the argument that’s coming about that aspect of Zeihan’s model. Isn’t the Mississippi River a pretty big deal? And those oceans on the east and west coasts seem like nice borders. Indeed, while he gives us many reasons why there was always going to be an American superpower, geography is central to his story. He has lots to say about America’s internal river systems, farmland, and other geographic features. What mountain barriers exist are apparently better than in other countries in terms of allowing internal transport; the Rockies have major passes, several of which have large cities within them, and the easiest pass in the Appalachians featured America’s first National Road, 130 miles of buried logs that linked two rivers, and thus the east coast with the best farmland in the world. As we saw with his exposition on the Nile, Zeihan puts a lot of emphasis on the value of river systems. He argues that America’s waterway network alone should be sufficient for “global dominance.” The numbers he provides in support of this point are impressive. For example, “the Mississippi is only one of twelve major navigable American rivers. Collectively, all of America’s temperate-zone rivers are 14,650 miles long. China and Germany each have about 2,000 miles, France about 1,000. The entirety of the Arab world has but 120.” He praises US barrier islands that mitigate oceanic destruction and effectively create another river system, as well as the fact that the river system is an actual network. All of this gives America more internal waterways than the rest of the world combined. Thus, we get cheap transportation for “Nebraska corn or Tennessee whiskey or Texas oil or New Jersey steel or Georgia peaches or Michigan cars,” enabling savings that “can be used for whatever Americans (or their government) want, from iPhones to aircraft carrier battle groups.” America doesn’t have to spend on artificial infrastructure, like German roads and rails, but when it does, the competition from the rivers keeps transport costs low. Cheap internal transportation has other benefits. “It’s a recipe for small government and high levels of entrepreneurship,” as small government keeps taxes low, leaving people with plenty of capital. Some people may think of the American consumer with disdain, but it isn’t a new phenomenon. Zeihan points out that America has been the world’s largest consumer market “since shortly after the Civil War.” His observation about a robust food supply forming the base of any civilization bodes well for America, which apparently has the largest connected stretch of quality farmland in the world (the Midwest), the value of which is exponentially increased by the fact that it overlaps with so many of these amazing river systems. It isn’t just the Midwest that he gushes over. California’s Central Valley and the Sacramento River, and Washington and Oregon’s farmland with the Columbia and Snake Rivers get praise. The only major farmland more than 150 miles from a navigable waterway is some of the Great Plains near the Rockies. ***** Zeihan provides a reminder that national security is actually a thing, and that at its most basic level, it’s about protection against invasions. It was something of a shock reading about America’s land borders in that context. “As Santa Anna discovered during the Texas Independence War, there is no good staging location in (contemporary) Mexican territory that could strike at American lands.” And, “Canada’s border with the United States is much longer, more varied, and even more successful at keeping the two countries separated,” thanks to mountains and thick forests over much of it. The mid-continent lands are much more connected, but Zeihan frames these Canadian areas as basically American; they’re physically separated from Canada’s core eastern provinces, so trade with them is weaker than with the closer American states. Then there are the oceans. As much as Zeihan loves deserts for protection, he loves oceans more (particularly in a post-World War II world; more on that below). We get a story about the War of 1812 nearly splitting America into three when the British attacked Baltimore. America learned about “strategic vulnerability and sea approaches,” as the attack “on Baltimore—indeed, the entire war effort—would have been impossible without launching grounds in Canada and the Caribbean.” American foreign policy since then can be understood with respect to this lesson. Zeihan cites it as inspiration for America’s steps to make its ocean borders truly impenetrable, such as working to sever Canada from Britain, and the imperial-era acquisitions of Alaska, Hawaii, Midway, Puerto Rico, and de facto control of Cuba (preventing enemies from cutting off Mississippi River-based trade from the rest of the world). There’s more to Zeihan’s being awestruck by America than his analysis of its balance of transport advantages. He argues that America has been the world leader for agriculture, technology, finance, and industry since the Civil War, and runs through a litany of reasons for its preeminence: America is like a continent-sized island (because of its effective land borders), which is always going to be a more natural naval power than a more landlocked country.
iproniazid

iproniazid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 06, 2024 and September 06, 2024. The archive places it in contexts such as "the antitubercular agent iproniazid, which, when administered in the tuberculosis ward, had patients rising from gloomy stumors to eat, and socialize". It most often appears alongside #MeToo, 21st century political dogmatism, Advanced Tax.

Reference entry
iproniazid
Mention count
1
Issue count
1
First seen
September 06, 2024
Last seen
September 06, 2024
September 06, 2024 · Original source
MAOIs are by and large considered Old School. The very first antidepressant discovered was an MAOI, the antitubercular agent iproniazid, which, when administered in the tuberculosis ward, had patients rising from gloomy stumors to eat, and socialize, “dancing in the halls tho' they had holes in their lungs.” MAOIs fell out of vogue when it was discovered that they interfere with tyramine digestion, and require a carefully controlled diet, with risks of severe hypertensive reactions.
Iskander

Iskander is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 29, 2022 and December 29, 2022. The archive places it in contexts such as "including 87% of its Iskander missiles". It most often appears alongside Adnan Ihsan Saeed al-Haideri, Adobe Illustrator, Ahmed Chalabi.

Reference entry
Iskander
Mention count
1
Issue count
1
First seen
December 29, 2022
Last seen
December 29, 2022
December 29, 2022 · Original source
Here’s a Ukrainian blog calculating how many missiles they think Russia has left. They say that Russia has used up about 51% of its total missile stockpile, including 87% of its Iskander missiles and 37% of its Kalibr missiles. I think this is consistent with Russia using up a lot of their best missiles in a starting barrage early on, then toning things down and conserving missiles better, and they still have some. Various intelligence analysts make different estimates of how many they still have, but it doesn’t seem like anyone is lying or making things up, least of all the newspapers which are just faithfully reporting what the analysts say and even adding in appropriate nuance.
iXL

iXL is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "Many schools use tools like iXL, Beast Academy and Amira"; "Math (learning new math; mostly on iXL)". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
iXL
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Same state curriculum, same worksheets, same pace. The school philosophy was “no acceleration—just go deep.” We knew this was the philosophy going in. The pitch was that instead of accelerating through the state curriculum the teachers would take their time with the kids and allow them to fully explore and master the content of each grade. When we asked for examples of what that meant in practice we were told things like: “Instead of reading more advanced vocabulary, the students will learn to read out loud and use emotion and character impressions. They will learn how to vary the timing of their reading like where and when to pause to create emotion in the listener”. That sounded reasonable! It sounded like more learning, but just different learning than what the state had mandated. In practice that was not what happened. In practice “deep” just meant “un‑measured.” Smart kids + small classes ≠ accountability. The kids had time to do music, lego building, theatre and Friday ski trips because they were all really bright. They didn’t need 6+ hours a day to learn the limited math required by the state, and since the school did not feel the need to advance faster than the state, there was no pressure to push learning at all – on anything really. There was no overall school curriculum. Every teacher did their own thing. While one first grade class had weekly spelling bees, the teacher in the other classroom did not believe in learning spelling at all. But it didn’t matter. The metrics they measured the kids on in both classes advanced “enough” that no one was concerned. Most time wasn’t spent on math or language anyway. Beyond the brochure activities like skiing and theater and the four hours of foreign language per week they split between Spanish and Mandarin (which was really a great opportunity for the kids who already spoke Spanish and Mandarin to have their egos flattered. I did not see any learning in either language class. I don’t see how you can teach a language a couple of hours a week to a group of 18 kids with skill levels from zero to fluency and expect to have any impact), a lot of time was spent on DEI. DEI was pitched as helping kids handle the emotions that often come from being sensitive gifted children (they called it “Synapse”). In practice my oldest daughter got four years of learning about the basic ideas of Martin Luther King Junior and Rosa Parks, a rough understanding that some people are non-binary, and a great deal of anxiety every time I left the water running while I was brushing my teeth. The talent drain In Spring 2024 the “intermediate-school” head resigned, as did the 40+ year veteran science teacher we had been looking forward to our daughter having, the beloved tech teacher who had built a her own proprietary “learn to type” software, plus half the lower‑school faculty. Our oldest was going to be entering fourth grade; her incoming roster read like a rebuilding year for a professional sports team. It was possible we could get her into a middle school that would feed into a top tier high school, but those did not start until 5th grade. Our best option looked like “suck it up and accept whatever we had for at least a year”. One option was to do something radical. We considered taking a GAP year and traveling the world with an organization called “Boundless” but decided the timing wasn’t right. Earlier in the year we had started exploring moving to the charter city of Prospera. There is a Montessori school there that seemed like it might be alright. And we could surround the kids with an interesting group of people (and live on the beach!). But by the spring we had ruled it out. There did not seem to be many families as part of the community and we were not comfortable with the risk profile based on what was happening with the conflict between Honduras and their charter cities. Then I stumbled across Alpha: Two‑hour mornings, life‑skills afternoons, claims of 2x learning. Marketing copy is cheap; still, the promise was different enough to warrant due diligence. The initial plan was to fly some of the kids to Austin for an Alpha summer camp for a week in June – just to try it out. But once we started exploring more my wife asked me: “Could we actually move to Austin and try it for a year? Based on what is happening at the kids' school, this might be the year to try it.” So over eight weeks we flew to Austin five times – conversations with admissions and school heads, real estate searches, kids doing shadow‑days. Every parent we spoke to was very impressed with the school. Their kids really were advancing at 2x+ speed – and no one believed it was just a “selection effect”. And every guide I spoke to was extremely impressive themselves. They reminded me of the staff you run into when visiting Disney World. They all seemed “full faced” and fully-engaged. When I asked the head of admissions how they found such good staff he told me their compensation was fully transparent. “Associate Guides” were paid $60,000/year (vs the $40,000 average for Austin teachers), “Full Guides” made $100,000 and the five “Head Guides” in the school each made $150,000. They were able to both poach the best teachers from other schools, but also bring exceptional people into teaching that would not have considered it otherwise. It also let them have very high expectations for teachers once they were hired. We pulled the trigger in July. New house. Admissions letter signed. Moving truck (plus car-mover) scheduled for October. Worst case, it would be a one‑year sabbatical from stagnation. The hypothesis I carried south Elite private school attendance buys you smaller classes, brighter kids, and fancier field trips – not academic acceleration. If Alpha was real, we’d see that differential, measurable impact by Christmas – that was when we would need to decide if we would cut bait and re-apply to schools back home (and sign the kids up for more IQ-tests. The school would not accept old ones). That prior—show me velocity, not polish—is the lens through which the rest of this review should be read. Part Two: A History of Alpha Note: This is my best attempt at piecing together the history of the school based on conversations with co‑founder MacKenzie Price, high school head Chris Locke, Alpha staff, and Alpha parents; All dates are estimates and I am SURE I have gotten some details wrong. I will come back after the fact in the comments and make corrections as I hear from the people involved with corrections. 2013 – 2017 | Garage‑School to “Alpha” MacKenzie Price, then a mortgage broker in Austin, wasn’t impressed by the city’s gifted programs. She invited a small number of neighbourhood kids (including her two) into a makeshift microschool that ran two intense, teacher‑led academic “sprints” each morning, then “life‑skills” projects after lunch. Joe Liemandt — Founder of Trinity Technology, ESW Capital billionaire and family friend (MacKenzie’s husband worked for him) — kept his own children in conventional private school until he saw the qualitative improvement in the life skills of MacKenzie’s kids. He decided he wanted his kids to join MacKenzie’s but he wanted to take the project to the next level. Sometime around 2014-2017 he joined MacKenzie as a co-founder and started writing checks. Alpha recruited more students and guides and the operation jumped from location-to-location looking for a larger permanent home. 2017 – 2020 | K-8 Expansion and 2-hour focus Alpha grew to roughly 90 students from K‑8 and stabilized. Morning “core blocks” were still teacher‑driven (20‑minute bursts, 5‑minute breaks, rinse, repeat), but focused on students engaged in exercises with rapid feedback (not lectures). Afternoon workshops covered “life skills” like how to give and receive feedback or public speaking. I have not seen academic data from this time period, but when I spoke to Chris Locke, head of Alpha’s high school (which launched around 2020), he told me the kids coming into his 9th grade program were “fine,” academically – it was their life skills, confidence, and ability to engage with adults and their peers were exceptional. At this stage no AI, no dashboard, no 2x learning, no portal — just better ratios and focused pacing and the result was well balanced kids who were enjoying their education experience (even if they were unexceptional academically). 2020 – 2022 | Platform Era Begins Somewhere along the way Liemandt hired a small engineering team to stitch together edtech learning tools. Many schools use tools like iXL, Beast Academy and Amira. Those tools fit in well with the 2-hour structured approach Alpha was using. The “platform” Liemandt’s team built was meant as a tool to free up guide time so that students could be more self-directed. The dev team stitched together the preferred off‑the‑shelf apps behind a single login, and built out tracking and dashboards so guides (and students) could easily see how they were progressing. This also gave the curriculum team (there was a curriculum team now) data to understand where students were spending their time, what tools were working, and which weren’t as effective. The Alpha Portal was born. Not only did it increase efficiency, it provided data to iterate with. Chris Locke saw the curve change incrementally: each new cohort of ninth‑graders under the new tech-enabled learning platform came in a little stronger academically. The “life skills” were now being matched by the “academic skills”. 2022 | Expansion and Iteration By having access to Alpha kids post-graduation in the high school, Locke could send feedback back to the elementary school.The kids coming out of the new program were now killing it academically on Math, Language, and Science, but they were still weak on things like History and Geography. He fed that type of information back to the curriculum designers, who iterated and improved the program. Soon, in addition to the core platform that directed students to third-party tools, the tech team was building proprietary “Alpha” tools themselves. The flagship of the in-house tools was “AlphaReads”. AlphaReads requires students to read progressively more complicated passages, followed by answering reading comprehension questions. In addition to helping the kids improve reading skills, Alpha uses it to push types of content. Instead of classes in history, geography, economics and political science, some of the reading passages will cover that material (in addition to learning how to read and understand Shakespeare and Proust). The success of the 2-hour learning platform was giving the Alpha founders confidence. Liemandt in particular wanted to see if the program had legs beyond the elite group of students being educated in Austin. Alpha’s first external test in August 2022 in Brownsville, TX – a small community on the Mexico border with less than half the per capita income of Austin. SpaceX had recently launched Starbase in Brownsville in 2014 and the employees there were not happy with the existing school options. Someone at SpaceX approached Alpha and asked if they could launch a new campus for their employees. It is unclear if any money changed hands, but when Alpha launched their Brownsville campus (available to SpaceX employees and any other locals who are interested) tuition was only $10,000 (vs $40,000 at the main Austin campus); incoming students trailed national academic standards by over a year. But after nine months on the Alpha program the first cohort of students had caught up and surpassed the national average, and they kept accelerating, achieving an average learning velocity of ~2× the national average (see section four for what that means). Brownsville was Alpha’s attempt to show that their model wasn’t just rich‑kid selection effects. Spring 2024 | Field Pilots & Ukraine Trip Alpha tuition is high for the Austin area ($40,000 vs average private school ~$10,000-$15,000), but unlike most private schools tuition is all-inclusive. There are no extra fees for computers or field trips. There are no silent auctions or appeals for donations. This “no extra fees” allows the school to do some pretty ridiculous things. In the first half of 2024 Alpha sent a group of students to Poland to help launch a 2-hour learning pilot among Ukrainian refugees. Students did not pay to go on the trip. But students also did not have a “right” to go on the trip. They had to earn it. In addition to being on top of academic and non-academic expectations, students who wanted to participate had to learn basic Ukrainian so they could interact with the students in Poland they were meant to be helping. By not linking the opportunity to payment, the school could instead link it to behavior and achievement. This year a group of kids who learned to sail during the school year are going on a sailing trip through the Caribbean – for no additional fees to the parents. I also heard that around this time Alpha began testing the 2-hour learning platform at a facility for juvenile delinquents in Florida. I heard that from one individual who was not directly involved and I have not found any written documentation on it, so unclear if it worked, it was a one off, or if it even happened. But it fits into the pattern of Alpha at this stage: “We know this program works for a specific type of kid. Let’s find out how broadly it is applicable. Can it work for everyone? Is it the solution for learning and education for the world?” Fall 2024 | “Pick‑Your‑Afternoon” Specialist Schools MacKenzie told me that there was consensus among the current parents of Alpha that the 2-hour learning program was exceptional and was making a huge difference with their kids. Their kids were all learning at breathtaking speed in a very condensed period of time. But there was NOT consensus about what the kids should be doing in the other 22-hours of the day. Some parents wanted to utilize the platform’s capabilities to go even faster. Some wanted their kids to just chill out and enjoy the rest of their day – let kids be kids. Others wanted their kids to use the freed up time to do sports, or study music. It was clear to her that “learn more faster in a short period of time” was a universal desire. But beyond that it was unclear what the “right” solution for the rest of her program was. You can make the morning ultra-personalized, but if the goal of the afternoon is socialization that you are missing in the morning, you need to have some sort of alignment on how to spend that afternoon. That challenge led to Alpha’s 2024 expansion into specialty schools. Three micro‑campuses opened August 2024: GT School (Georgetown, TX) — Alpha’s “Gifted and Talented” School. Higher admissions bar; higher academic expectations; Afternoon programming focused on excelling in “academic competitions” like chess, go, debate, public speaking, robotics, programming and Quiz Bowl.
Math (learning new math; mostly on iXL)
Izanami

Izanami is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "Larry Ellison christened his yacht Izanami". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Reference entry
Izanami
Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
49: Did you know: Larry Ellison christened his yacht Izanami for a Shinto sea god, but had to hurriedly rename it after it was pointed out that, when spelled backwards, it becomes “I’m a Nazi”. (next year’s story: Elon Musk renames his yacht after being told that, spelled backwards, it becomes the name of a Shinto sea god).
İlknak

İlknak is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "İlknak publishing the commitment on their website". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
İlknak
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
J&J

J&J is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 16, 2021 and February 16, 2021. The archive places it in contexts such as "we’ll find that P/M, Novavax, AZ, and J&J all cut deaths". It most often appears alongside AIDS, AZ, B117 strain.

Reference entry
J&J
Mention count
1
Issue count
1
First seen
February 16, 2021
Last seen
February 16, 2021
February 16, 2021 · Original source
...at vaccinated people would also be less likely to transmit the virus to others if they do get it. Prediction: 55% chance that later, when we have great evidence on this, we’ll find that P/M, Novavax, AZ, and J&J all cut deaths from all extant strains by at least four-fifths. When the fifth wave strikes in late spring/early summer, some of the population (~50%?) will be vaccinated, another part...
Jaguar

Jaguar is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "some Jaguars ... were made of aluminum". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Jaguar
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Musk’s word choice there—“obvious decision”—goes a long way toward explaining how he operates. Yes, the car needed to be light, and, yes, aluminum would be an option for making that happen. But at the time, car manufacturers in North America had almost no experience producing aluminum body panels. Aluminum tends to tear when worked by large presses. It also develops lines that look like stretch marks on skin and make it difficult to lay down smooth coats of paint. “In Europe, you had some Jaguars and one Audi that were made of aluminum, but it was less than five percent of the market,” Musk said. “In North America, there was nothing. It’s only recently that the Ford F-150 has arrived as mostly aluminum. Before that, we were the only one.”
Janssen

Janssen is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "gotten money from Janssen". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
Janssen
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Jarrow

Jarrow is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "price per dose to the same as Jarrow"; "Others like Life Extension, Jarrow, and NOW have most things pass with only some failing"; "I trust Nootropics Depot, Thorne, NOW, and Jarrow". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Jarrow
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
So anyway, that's the situation. To say I am frustrated doesn't even scratch the surface. However, I can only fight so many fights at once. Even so, we were able to add a 540ct bottle that gets the price per dose to the same as Jarrow and LEF, while still complying with the TMLA and MAP agreements. Ours will also always have what we claim.
NOW has their own in-house lab, and they have been trying to clean up the standards of the industry for a while. We have had a couple things of theirs fail, but only for content lower than label claim, not fake or impure or anything like that. So while I wouldn't say trust everything from them 100%, NOW is one of the better ones in this industry seemingly trying to make things better. I also have more trust for Thorne than most […] every single brand we have tested so far has had at least one thing fail, save for Thorne. Some of the brands have almost everything fail. Others like Life Extension, Jarrow, and NOW have most things pass with only some failing. It's a crap shoot.
Botanicals are more complicated. Commonly-used botanicals from reputable brands are usually about as trustworthy as vitamins, but there are lots of complications around extraction processes and sometimes you might get 50% more or less than you thought. Less-commonly-used botanicals are less clear; you still will rarely find outright sugar pills, but you may find people bungling the chemistry, not caring too much about exact amounts, or selling mushroom mycelium instead of fruiting body. “Male enhancement” products are their own special class of danger zone, as are anything that’s been featured on The Joe Rogan Experience; you should be extra careful to buy from only the most reputable companies. I trust Nootropics Depot, Thorne, NOW, and Jarrow, in that order, but you’ll want to do your own research and maybe check ConsumerLab for the particular product you’re buying.
Jetson One

Jetson One is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 12, 2022 and October 12, 2022. The archive places it in contexts such as "New flying car project, Jetson One". It most often appears alongside 538 deluxe model, @rcafdm, Andres.

Reference entry
Jetson One
Mention count
1
Issue count
1
First seen
October 12, 2022
Last seen
October 12, 2022
October 12, 2022 · Original source
7: New flying car project, Jetson One, advertises 20 minutes of flight time (at up to 63 mph) per charge, ~$92,000, no pilot license or skills necessary, technically available now-ish but sold out until 2024.
Johnson & Johnson

Johnson & Johnson is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 07, 2021 and February 07, 2021. The archive places it in contexts such as "the Johnson & Johnson vaccine needs to be approved faster". It most often appears alongside slatestarcodex.com, Twitter, WebMD.

Reference entry
Johnson & Johnson
Mention count
1
Issue count
1
First seen
February 07, 2021
Last seen
February 07, 2021
February 07, 2021 · Original source
...the front page of the newspaper! I think this is broadly in keeping with it being easier to produce illegible knowledge (an expert posting on Twitter that they think the Johnson & Johnson vaccine needs to be approved faster, or a random person looking at the evidence and deciding this) than legible knowledge (that same fact making it onto the front page o...
...on the front page of the newspaper! I think this is broadly in keeping with it being easier to produce illegible knowledge (an expert posting on Twitter that they think the Johnson & Johnson vaccine needs to be approved faster, or a random person looking at the evidence and deciding this) than legible knowledge (that same fact making it onto the front page of a newspaper). Probably one solutio...
JOT

JOT is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2025 and September 19, 2025. The archive places it in contexts such as "then tried again to build his JOT word processor". It most often appears alongside 1987, 1988, Adleman.

Reference entry
JOT
Mention count
1
Issue count
1
First seen
September 19, 2025
Last seen
September 19, 2025
September 19, 2025 · Original source
Eric Hill, a 15-year-old hacker and indicted felon, who “had been dismissed by the judge with admiration.” In Swarthmore, Nelson hoped his decades-old dream of Xanadu would finally materialize. 5. Developing Xanadu Ted Nelson had built Project Xanadu into, for lack of better terminology, a cult.8 He writes: We all were deeply concerned about the Bad Guys, who we saw as a combination of IBM and the government. (The others were all Libertarians, I still called myself a Cynical Socialist.) The Bad Guys would spy on people, withhold and block information, and give us inferior hypertext. We had to Do It Right, to help prevent this. This meant using the standard business defenses—especially non-disclosure agreements (I made all of them sign) and secret proprietary algorithms. The Xanadians had a messiah—Ted Nelson—a gospel—Computer Lib—a persecution complex, a fearful dystopia—“inferior hypertext”—a hopeful utopia—Xanadu—and utter secrecy. Just six dudes in a rented house near Philly, building the internet, hiding from the Feds, signing NDAs, and saving the world. Nelson spent a summer explaining the project to his team in its entirety. By the end, Gregory, Miller, and Greene were the only ones left. They told Nelson, “We’ll do it,” and moved to another suburb, where they finally began to work on an implementation of Xanadu. The three quickly figured out a new system that would allow users to reference and link to specific parts of a file—they called these links tumblers, and made them work with transfinite numbers. Suddenly, transclusions were really possible. But after only a few early successes, the team’s progress stalled completely. Greene and Miller were young and left for jobs elsewhere, and so Gregory was left working on Xanadu alone. Nelson, meanwhile, ran a magazine called Creative Computing for a while, then tried again to build his JOT word processor—this time for the Apple II—then spent a year in San Antonio pitching a watered-down version of Xanadu (rebranded as “Vortext”) to a tech company called Datapoint. Datapoint wasn’t buying, but kept Nelson on in some sort of fake, primitive email job anyway. Gregory kept working on Xanadu in Philadelphia, slowly running out of money. Ted Nelson held an “Ecstasy party” in San Antonio: “A number of us floated down the river on inner tubes. It was quite lovely.” In 1987, like he did every year, Roger Gregory went to The Hackers Conference in Saratoga to show off the latest unimpressive version of Xanadu. There, he met a man named John Walker—founder of the wildly successful Autodesk—and pitched the project to him. Incredibly, Walker was interested, and after tense negotiations with Nelson, agreed to fund Xanadu in earnest. Beginning in 1988, Autodesk poured millions of dollars into the project, and a programming team led by Gregory finally started to make real progress. Walker said of Xanadu: “In 1980, it was the shared goal of a small group of brilliant technologists. By 1989, it will be a product. And by 1995, it will begin to change the world.” Sweeping rhetoric—clear deadlines. The team came nowhere close to meeting them. Infighting broke out between two factions—while Gregory simply wanted to patch together his old C code, insisting his product “was within six months of shipping,” the whiz-kid Mark Miller came back from his new job at Xerox PARC, alongside a half-dozen of his closest friends, and insisted on a perfectionistic rewrite in a more flexible language, Smalltalk. The PARC faction began to drive Gregory up the wall. According to Nelson, it got to the point that he “was throwing things and acting crazy.” So Nelson called John Walker, the two “summoned Roger to meet [them] at John’s house at Muir Beach, and Walker told Roger he was no longer in charge.” Miller took over and began the rewrite in Smalltalk. Walker’s deadline came and went, and the team delivered nothing. Xanadu’s offices descended into chaos—Miller anointed two PARC programmers to be “co-architects,” and the three of them increasingly left the rest of the team out of the loop. For four years, Miller dawdled about, adding features, giving them clever names (files were “berts,” after Bertrand Russell, and so, for symmetry’s sake, royalty-generating transclusions became “ernies”), and never building them.9 Meanwhile, Ted Nelson was living on a houseboat, attending sex retreats and Keristan orgies, and giving talks in Singapore. He recorded a new soundtrack for his student film, the one from 1959. In 1992, Autodesk’s stock cratered, and they divested entirely from Xanadu. Miller lamented that his program was just six months from completion. Ted Nelson started a film studio to make a movie with Doug Engelbart, then left for Japan to get a PhD. Xanadu’s code was open-sourced in the late 90s. 6. The World Wide Web In March 1989, a British computer scientist named Tim Berners-Lee, working at CERN, wrote a proposal for a system unifying hypertext and the internet. It was ignored. In 1990, Berners-Lee resubmitted his proposal, it was accepted, and he began to work on the World Wide Web. The WWW had a number of advantages over Xanadu: It was much simpler—Ted Nelson wrote of it disparagingly: “Where were annotation and marginal notes? Where was version management? Where was rights management? Where were multi-ended links? Where were third-party links? Where were transclusions? This ‘World Wide Web’ was just a lame text format and a lot of connected directories.” As it turns out, it’s much easier to build a lame text format and a lot of connected directories!
Jukebox

Jukebox is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 20, 2021 and May 20, 2021. The archive places it in contexts such as "OpenAI’s Jukebox , which is basically GPT-3 for music". It most often appears alongside 5D Chess With Multiverse Time Travel, AI X-Risk Research Podcast, Alignment Research Center.

Reference entry
Jukebox
Mention count
1
Issue count
1
First seen
May 20, 2021
Last seen
May 20, 2021
May 20, 2021 · Original source
4: I’m very late here, but you might still enjoy OpenAI’s Jukebox, which is basically GPT-3 for music. Train it on Elvis, then make it write new songs on his style. Or feed it the first few verses of Never Gonna Give You Up and make it guess what the rest of the song sounds like. Or just have Celine Dion sing a song about being a music generation algorithm produced by OpenAI.
Kalashnikov rifle

Kalashnikov rifle is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "He’s since gotten a Kalishnikov rifle and is patrolling the streets of Kiev". It most often appears alongside Achilles, Afghan, America.

Reference entry
Kalashnikov rifle
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
No direct inline source block was recovered for this mention.
Kalibr

Kalibr is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 29, 2022 and December 29, 2022. The archive places it in contexts such as "and 37% of its Kalibr missiles". It most often appears alongside Adnan Ihsan Saeed al-Haideri, Adobe Illustrator, Ahmed Chalabi.

Reference entry
Kalibr
Mention count
1
Issue count
1
First seen
December 29, 2022
Last seen
December 29, 2022
December 29, 2022 · Original source
Here’s a Ukrainian blog calculating how many missiles they think Russia has left. They say that Russia has used up about 51% of its total missile stockpile, including 87% of its Iskander missiles and 37% of its Kalibr missiles. I think this is consistent with Russia using up a lot of their best missiles in a starting barrage early on, then toning things down and conserving missiles better, and they still have some. Various intelligence analysts make different estimates of how many they still have, but it doesn’t seem like anyone is lying or making things up, least of all the newspapers which are just faithfully reporting what the analysts say and even adding in appropriate nuance.
Kalishnikov rifle

Kalishnikov rifle is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "He’s since gotten an Kalishnikov rifle". It most often appears alongside Achilles, Afghan, America.

Reference entry
Kalishnikov rifle
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
e. Former oligarch Petro Poroshenko is Ukraine’s unpopular ex-president, recently placed under something like house arrest pending a corruption trial. He’s since gotten an Kalishnikov rifle and is patrolling the streets of Kiev against Russian invaders.
Keeper

Keeper is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
Keeper
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
Chris is looking dejected. “Man, I haven’t even made it to engaged-stage-zero yet. I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing. Do you think I should edit my dating doc?”
Kelley Blue Book

Kelley Blue Book is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 11, 2021 and December 11, 2021. The archive places it in contexts such as "You can think of it as a Kelley Blue Book for buildings". It most often appears alongside /r/georgism, ACX community, Aggregate Land Rents, Expenditure on Public Goods, and Optimal City Size.

Reference entry
Kelley Blue Book
Mention count
1
Issue count
1
First seen
December 11, 2021
Last seen
December 11, 2021
December 11, 2021 · Original source
Well managed, transparent, and adequately funded mass appraisal procedures Everyone is in further agreement about the three basic "approaches" to value estimation: the market approach, the cost approach, and the income approach. The Market Approach This is the most common approach. You gather a bunch of information about comparable properties, look at past selling prices and rents, and make adjustments for differences. This is greatly aided by modern computerized databases, as well as Geographic Information System (GIS) mapping and visualization tools. Remember those spot checks I did in Part I to estimate the value of the land under a building in San Francisco using a nearby, similarly-sized empty lot? That was me (crudely) using the market approach. The Cost Approach In this approach, you estimate the cost of the buildings minus depreciation. Professionals that value residential and commercial buildings often rely on Marshall & Swift's Valuation Service. This is a fancy calculator where you plug in all the different characteristics of your building, and it spits out a cost estimate. You can think of it as a Kelley Blue Book for buildings. Once you have the cost of your building, you apply certain widely-accepted depreciation formulas based on its age. The cost approach has two chief limitations. The first is that it requires a lot of detailed information about the building. The second is that the cost to build something isn't necessarily the same as what it would sell for in today's market. Therefore, this approach tends to overestimate building values and underestimate land values, as discussed in detail in Part I. The Income Approach In this approach, you look at the net income (rent - expenses) that a commercial or residential property generates and then use the prevailing capitalization rate of the area to get the property value. You typically use this formula: Value = Income / Rate This gives you the total property value, and from there, you can use one of the other two approaches to separate land value from building value. Crucially, any observed land or property tax needs to be factored into the observed "income" portion. Even if the state is collecting the tax, it's part of the flow that originates from the property, and thus affects the full untaxed market value of the property. Naively you might expect a 100% Land Value Tax to drive itself to zero because it also drives down the purchase price of the land to approximately nothing. To avoid this, you figure out the capitalized value of the LVT that's already been applied to get the untaxed land value. These are the basic methods that we've used to value properties "by hand" over the last century, and there are many who claim that these are good enough. As for separating land from buildings, Ted Gwartney prefers to estimate the value of land directly whenever possible and derive the building value as a residual. He claims it's easier to assess land than buildings, because in most cases, the value of land is derived almost entirely from the location. Land doesn't have as many fiddly variables, like how much damage your roof took from the last hailstorm and whether you've remodeled your bathroom in the past five years. But let's dive deeper. 2. Assessing the Assessments Okay, so once you've made all your assessments, how do you ensure they're accurate? You test them. We have two main signals: ongoing transaction data from the market, and complaints from property owners about the assessed values. The typical way you compare yourself against market transactions are "Ratio Studies", which you can read more about in this IAAO paper on the subject. As for complaints, you'd think property owners would always complain out of pure self-interest, but apparently, only a minority do, and assessors actually build in an expectation for a certain number of complaints as a chief source of feedback. If complaints are below a certain threshold (2% according to Hefferan and Boyd), that's apparently a sign that you're doing well. During Ted Gwartney's seminar, someone asked him about what tends to drive objections: ATTENDEE: Can you tell us what fraction of property owner who request a lower assessment argue that their land assessment is too high? GWARTNEY: A very small number. Almost all of the adjustments that are made are made because of improvements. Most of the arguments when you go to an appeal is about the building, it’s condition, or what’s in it or whatever. Generally the land is accepted by people, they realize it’s fair by looking at what other parcels are assessed for and most people don’t argue it. They might say he has a better view than I do or whatever, but usually [the objection is] because there’s some physical difference or condition in the structure. So if the public accepts your valuations, and new market signals match your assessments, then they can be said to be accurate. But how precise do they need to be? Here's Gwartney's opinion: ATTENDEE: How accurate do assessments have to be to get the benefits of Georgism? GWARTNEY: You have a lot of wiggle room. It doesn’t have to be perfectly precise. The idea is to improve on what’s already being done. You get immediate feedback that what you’re working on is making good results. This is a part I'd like to know more about. Is plus or minus 5% of the true land value "good enough?" What about 15%? Or 1%? If land is under-assessed, then we basically have the same problem as the status quo, and we're not really any worse off. But if land is over-assessed, we might drive people off of it, which is bad. So it seems our main problem is not over-assessing the value of land. Georgists often talk about "100% LVT," but during practical discussions, it seems that their wildest dream is just to get as high as 85%. That would leave a pretty big safety margin for not over-taxing the land, even if you over-assessed it. Here's a graph. If you under-assess a property's land by 15%, the assessed value is 85% of the true value. Take 85% of that and now you're collecting 72.25% of land rents. If you over-assess a property's land by 15%, the assessed value is 115% of the true value. If you take 85% of that, you get 97.75%. Collect all that and you're still leaving 2.25% of the land rents on the table, but you're not going over. This is comforting, but frankly, all the evidence I've seen so far suggests that we're chronically and consistently under-assessing the value of land. But even if we can assess things accurately, it's a moot point if we can't afford to hire enough assessors to do the job thoroughly. 3. How Many Assessors do you need? Another critique about assessment is that you're going to need an army of property assessors peeking inside windows at all hours of the night, and that it's all going to be ruinously expensive. Here's a slide from Gwartney's presentation, which is itself taken from an IAAO conference. Gwartney says that when he was the assessment commissioner and chief executive officer in British Columbia, he had a staff of 690, and that this number has not changed significantly since then. British Columbia has a population of about 5 million, so that's 1 assessment officer for every 7,250 British Columbians. For context, the IRS has a staff size of 74,454, or about one IRS agent for every 4,425 Americans. I don't have data on how many property tax assessors the USA has in total, but the above slide suggests British Columbia's figure is on the high end. As for how you actually do assessments, sure, you can send out an army of assessors to value each and every property in your jurisdiction by hand. However, not only is that labor-intensive, it's also a recipe for inconsistency. Whatever method you're using to value properties needs to be consistent and standardized across all properties, so you don't have sharp discontinuities on the assessment map that are due solely to differences between Assessor Fred and Assessor Sally's personal methodologies. Thankfully, we're living in the modern age, and we have some fancy new tools at our disposal. 4. Modern Technology Georgists were doing split-rate assessments to allegedly good success long before the rise of the computer, such as J. J. Pastoriza's effort in setting up a Georgist tax regime in Houston, Texas in 1911. Today, we have spreadsheets, property value databases, GIS mapping visualizations, regression analysis, machine learning...the works. According to Gwartney, the Canadian province of British Columbia has revalued all its land and all its property on an annual basis simply by using computers and market analysis, ever since he first helped them set up their system back in 1975. Not every jurisdiction revalues their land this thoroughly and this often, but Gwartney says there is no significant technical or staffing barrier standing in the way. Gwartney has been retired for some time, so his seminar didn't cover all the latest cutting-edge techniques that have come out in the last few years. Let's look at some recent papers and see what new tools assessors have to play with. The first on my list is Land Value Appraisal Using Statistical Methods by Kolbe, Schulz, Wersing, and Werwatz (2019). This is a study on mass appraisal techniques using real estate transaction data from Berlin, Germany. It claims that not only are the results cheaper and faster to generate than those done by conventional property assessment methods, but they are also no less accurate than those done "by hand" by experts. Kolbe et al. assert that, provided you have access to high quality market transaction data, you can perform accurate and efficient mass appraisals of land values. They chose Berlin because it "has a very effective system of property transaction data collection and storage," in contrast to other parts of Germany. They cite some prior work by Almy (2014) studying Canada, the Netherlands, and the United States, suggesting that the assessment cost per property can be brought down to 20 Euros–25 times cheaper than what some other people (Fuest, et al. (2018)) assert. Given an average tax receipt of 2,000 Euros per property, this means that the assessment cost should represent only about 1% of the funds raised. Is that good? Let's take this assertion at face value for the moment and compare it to the cost of the IRS. Federal tax receipts in 2020 were $3.42 trillion, and operation costs for the IRS were $12.3 billion, or 0.36%. However, the IRS outsources most of the labor of tax preparation to the taxpayers themselves, with compliance costs estimated between $200 billion and $400 billion a year, to the delight of Intuit. Add that up and the total cost of federal tax collection to the economy is anywhere between 6-12% of the amount it raises. And what about sales tax? According to a 2006 report by PriceWaterHouseCoopers: The study finds that the national average annual state and local retail sales tax compliance cost in 2003 was 3.09 percent of sales tax collected for all retailers, 13.47 percent for small retailers, 5.20 percent for medium retailers, and 2.17 percent for large retailers So a compliance cost of 1% would be way more efficient in terms of cost collection than the other two most common forms of taxation, and taxpayers don't even have to do anything themselves, other than pay the bill. Alrighty, how about the accuracy? The authors cite two international examples, Australia and Lithuania, as among the few countries in the world that have both a Land Value Tax and statistical methods for mass appraisals. Hefferan and Boyd (2010) assert that objections to assessments from property owners in Australia are less than 1%. I'm willing to buy the improved efficiency claims just by taking a look at some methodologies. It seems reasonable that computerized records and algorithms can cut costs significantly; the real question is if you're trading off accuracy. The other papers I found on the subject are Bencure, et al (2019) in BayBay City, Philippines, Kilić, et al (2019) in Croatia, Yalpir & Unel (2017) in Konya, Turkey, and Raslanas et al. (2014) in Vilnius, Lithuania. Let's dive in and examine some methods. 5. Mass Appraisal Methods Here are some of the latest mass appraisal methods cribbed from the research papers listed above. All of these are based on taking market transaction data, plotting them out on a map, and running computations over them to estimate valuations for the properties you don't have known values for. Furthermore, all of these methods are able to value land and building values separately. Multiple Regression Analysis This paper by Yalpir and Unel out of Turkey gives a straightforward example of using Multiple Regression Analysis for land valuation. For those of you who didn't study math, let me explain regression analysis. This is a family of mathematical models where you basically take a data set, ask the question "what mathematical formula would best fit this data," choose a basic equation model, and then have a computer search for a set of coefficients that "best fit" that curve to the data with the least amount of error. The simplest example is using linear regression on a scatterplot of observed data points to fit a trend line. This is a common exercise in freshman physics and statistics classes. You can use more complicated versions of this numerical method to take a big bag of observations (real estate sales) and use "multiple regression" to tease out dependent variables (land value and improvements value) based on the independent variables (size, location, age, number of bedrooms) of your observations. In this case the team identified about a hundred different factors that can affect the price of a property: Then you create an entry for each property, fill in the values for each of those characteristics, and run it through the regressor. Take note of how many of these factors start with the words "proximity to." Each of these can be calculated automatically just by knowing where the property is on a map, and each of them is an independent contributor to the value of the property's location. The next step is to generate individual "index maps" that combine various related features into combined heat maps. Then you run everything through and see if it works. You can get the land share of the final value by combining the contributions of all the individual factors that you associate with "land," such as proximity to important things. In the verification section the authors say: As a result of the analysis, since the significance level (0.000) p <.05, corresponding to the F values in the ANOVA test, indicates that the regression analysis is appropriate and the models are significant. The criteria that make up the model account for about 85% of the market value and 15% cannot be explained for reasons such as economic, non-existent data and unearned income. Unfortunately, they don't say anything about how accurate their model is for assessing land values specifically. Otherwise, this is a pretty good example of using the Multiple Regression method for estimating the individual contributions of various factors to overall property values. Gwartney says Multiple Regression Analysis was a standard method he typically used, of which this specific paper is just one example. Nonparametric kernel regression This will be a method familiar to the programmers in the audience who have any experience with image processing algorithms. Here's an example from this old Gamasutra article: The basic idea here is to take a matrix of numbers, called a "kernel", and run that over every pixel in a source image. The kernel tells you how strongly to weight all of the source pixel's neighbors to compute a final result for that position. A simple "box blur" is a kernel where every value is 1 (meaning it averages the values of all neighboring pixels within a range). The more subtle gaussian blur illustrated above uses a two-dimensional normal distribution of values so that each pixel is most affected by those nearest to it. So let's apply the same principle to land valuations. If you have a map with lots of transaction data of pure land sales–defined as sales of either vacant land or teardown properties (where the building value is essentially zero)–then you can use a special kernel filter to smoothly interpolate land values across the region. So you basically have a smooth curve that mostly favors close-by points, tapers off a bit, and then disregards anything outside a certain distance entirely. The big assumption here is that land values change smoothly and do not change suddenly across very short distances. There are, in fact, locations with sharp jumps in value (any town with an "other side of the tracks," for instance). But for cases where we know a priori that land values change smoothly, this method is appropriate. No other prior restriction is placed on the form of the land value map, however, and this is why it's called "nonparametric." Here's an illustration. The outer box is the entire search distance that the kernel considers, and the circles represent the falloff of the curve itself. The size of the box is called the "bandwidth" and is set by the user. Everything outside of it will have zero influence on the kernel's output at any given location. This method operates on the same basic logic that I used when I hand-estimated the land value of that San Francisco house in Part I based on the value of the empty lot next door. However, it makes the whole procedure systematic. It can easily and accurately estimate the land value of a property with a big fat building on it simply by smoothly interpolating the known values of the nearby parking lots. Of course, it has limitations. First and foremost, it's a highly local operation, so if you have properties you're trying to value that don't have nearby pure land sales data, you can't really do much with this. Also, most people assume that city centers have less market transactions for undeveloped land than the countryside, as did I until I read that paper by Albouy in Part I. But in any case, this is just one method in your toolbox and might not be sufficient by itself. Its key advantage is that it works directly from true market data for land and doesn't need or want any other subjective data. In the end, basic kernel estimation just fills in the land value of unmeasured locations with a local weighted average of known locations. Nonparametric adaptive regression Kolbe, et al. build on the kernel regression method with a technique called Adaptive Weights Smoothing (AWS), which runs in several iterations and adds additional weight to any observed data points that are sufficiently close to the point being estimated. I'm not 100% sure about what all the math means, but it seems like it's basically a "smarter" version of the basic kernel method. Left: Nonparametric kernel regression, Right: Adaptive Weights Smoothing. I think the authors goofed and printed the same figure twice with different headings because they're identical if you overlay them in Photoshop. Semiparametric regression Now, the above two methods assume you have plenty of "pure" land sale records to work with. But if you're trying to work out prices in the city center, you've probably mostly got land and buildings mixed together. To do this effectively, we need more data, and this is where the "parameter" in "semiparametric" comes in. The model described in Kolbe et al. seems like a flavor of multiple regression analysis that takes the price, the location, and various characteristics of the building and feeds it into a regressor. But we've got "semi" parametric here. What does that mean? Well, if you already know how certain relationships between the data work a priori, it's better to enforce those relationships yourself rather than leave it to the computer. Here, we enforce the assumption that if two properties are right next to each other, then the value due to location is going to be essentially identical. This algorithm starts by ordering things geographically and then working out the differences in observed price by regressing on the difference between remaining property characteristics. In this method, the power of "location, location, location" is not something we're leaving to the regressor to discover by itself. Results of the Semiparametric regression method, we can see some significant differences from the simple kernel-based model. As you can see above, this gives you more detailed and likely more accurate results, and you're better able to assess the values of properties with buildings on them, even in the absence of pure land sales. This technique is more complicated and bakes in assumptions about the power of location, but otherwise doesn't assign subjective human weights to the various property characteristics. The chief human bias comes in the form of deciding which property characteristics are measured and made legible to the model in the first place. Okay great, but how accurate are the above three methods? Their main point of comparison is this thing called the "Bodenrichtwerte," or BRW. I think that means "ground-level-values" in English, and it's an expert-assessed map of land values for Berlin done the traditional way. The nonparametric kernel regression method has a correlation of 0.704 with the traditional method and has the added disadvantage that it's not able to produce estimates for the city center, only the outlying areas. Furthermore, the BRW map does show sharp discontinuities, which is another knock against the kernel method, at least for the city center. What about the iterative method? Kolbe et al. find that "the agreement between [Adaptive Weights Smoothing] land value estimates and, both, land prices and BRW land values is fairly good for all values of λ." Doing some quick checks, their values seem to be within about 85% of the BRW values. A different Kolbe et al. paper called Identifying Berlin's land value map using adaptive weights smoothing goes into more detail and claims to give "similar" values to that of the BRW. For the semiparametric method, they "found a strong positive correlation of 0.845" between their numbers and a previously expert-assessed set done using the traditional method. That sounds pretty good. It seems their margin for error is about plus or minus 15% compared to the traditional expert method. I'd like to see more direct comparisons against market transactions themselves, though, because if the prior expert assessments are wrong, then the main achievement here is improved efficiency, not accuracy. However, this method doesn't seem to be dramatically less accurate than the old way of doing things. The last three models came from the Berlin case study, where you have excellent market transaction data in an extremely wealthy and high-trust society. But what if you're trying to assess land in a developing nation with poor market transaction records, weak institutions, and widespread poverty? Innovative Land Valuation Model (iLVM) This is the particular name of the method described in Development of an Innovative Land Valuation Model (iLVM) for Mass Appraisal Application in Sub-Urban Areas Using AHP: An Integration of Theoretical and Practical Approaches by Bencure, Tripathi, Miyazaki, Ninsawat, and Kim. They used BayBay City, Philippines as their case study. Whereas the previous models are very "hands-off" and let the computer work out the relationships between prices and property characteristics, here you get expert human opinion directly involved in building the model, baking in weights that directly embody judgments like "properties next to major roads are more valuable." These judgments are based on expert opinions that presumably come from observed experience but are a priori judgments nonetheless. Here, look at this big complicated flowchart. The "Analytic Hierarchy Process" in the box on the left is a particular kind of method for getting experts to set weights. The authors give this reason for using it: Despite criticism pinpointed by other scholars, the AHP remains the commonly used in many research fields and practical applications. This is because the AHP: (1) overcomes human difficulty in making simultaneous judgment among factors to be considered in the model; (2) is relatively simple as compared to other MCDA [multi-criteria decision analysis] methods; (3) is flexible to be integrated in various techniques such as programming, fuzzy logic, etc.; and (4) has the ability to check consistency in judgment After identifying a list of "factors" that can affect land value, they group them into taxonomical buckets: Note that certain factors like "Coastline" appear in multiple buckets; this captures the various influences a characteristic can have. For instance, land on the coast tends to be more economically valuable because of tourism, shipping, fishing, etc., so that goes under "economic." But land that's next to the coast is also more likely to flood, so it also goes under "environmental." And then there are various land use restrictions that apply specifically to coastal areas, so it goes under "legal" as well. In this way, a single factor like "the property is on the coastline" can have both positive and negative effects on land value (e.g., it's more economically valuable but it also might flood, and there are certain things you aren't allowed to do there). The next step is to set down some rules for how sensitive each factor is to location and distance. So here we can see that the economic benefit of being on the coast is most strongly felt if you're within half a kilometer of the ocean, but the environmental effect (e.g., risk of flooding) is most strongly felt when you're within 0.03 kilometers. And so on and so forth. Your experts help you work out all these rules. Note that for a few of these factors (such as land use and slope), you use metrics other than distance (e.g. land use classification and grade). Then you take all that stuff and assign everything a value between 0 and 5. Your team of experts then uses this table to come up with a set of weights for everything. What essentially comes out of this is a big linear equation with a bunch of coefficients for every one of your factors, which is then broadly fit to the observed market prices. When you're done, you can take any property on your list, multiply each of its characteristics by its respective weight, run that through your equation, and calculate the predicted price of the land. So how accurate is it? The authors compare it to standard Multiple Regression Analysis and claim it fares better. The Root Mean Square Error is quite a bit less than MRA. In addition, I think it's also saying that the MRA algorithm decided that only four of the factors were significant and basically ignored all the rest. By contrast, iLVM was able to maintain contributions from all the factors, because it doesn't leave that decision to the computer. I'm not 100% sure; it's not clear from the paper. The authors claim that about 67% of the variability is explained by their model, but they note that there are some areas where the model can be off by more than a factor of 1.0 in either the positive or negative direction. One thing that's kind of fun about this model is that you can make neat graphs like this that show the individual contribution of each factor: The main downside to this model is that it relies on a whole lot of subjective expert opinion and can be questioned on that basis. That said, it can be cheaply deployed in a transparent and consistent way across a large area. You can see why that's attractive for a developing nation with weak institutions and poor market transaction records; the argument is that this is a significant improvement over the former status quo. I wonder how well this model performs when you feed it better market transaction data, and how that would compare against all the others methods under identical conditions. More research is needed. Rather than drag you through a bunch more research papers, I'll just leave these others I found cited in the above studies: Killić et al. (2019) - Fuzzy expert system for land valuation in land consolidation processes
Kelloggs

Kelloggs is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 28, 2023 and November 28, 2023. The archive places it in contexts such as "Gotten 3,000 companies including Pepsi, Kelloggs, CVS, and Whole Foods to commit". It most often appears alongside #57, 80,000 Hours, Adam D’Angelo.

Reference entry
Kelloggs
Mention count
1
Issue count
1
First seen
November 28, 2023
Last seen
November 28, 2023
November 28, 2023 · Original source
Gotten 3,000 companies including Pepsi, Kelloggs, CVS, and Whole Foods to commit to selling low-cruelty meat.
Kentucky Fried Chicken

Kentucky Fried Chicken is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 07, 2023 and June 07, 2023. The archive places it in contexts such as "National franchise stores, such as McDonald’s, Hardee’s, and Kentucky Fried Chicken"; "es, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken". It most often appears alongside 747, America, America Against America.

Reference entry
Kentucky Fried Chicken
Mention count
1
Issue count
1
First seen
June 07, 2023
Last seen
June 07, 2023
June 07, 2023 · Original source
The two parties are the most willing to have others fight under their banner. You can do whatever you want as long as you play under my banner and negotiate certain terms. National franchise stores, such as McDonald’ s, Hardee’ s, and Kentucky Fried Chicken, are available nationwide. The head office has no idea what they are doing other than selling the same goods. Americans implement the same ideas in politics and economics. The two parties are like a National franchise, with each branch doing its own thing to sell its products. . . It is sometimes unbelievable that two major parties that can dominate politics are so loosely organized.
KFC

KFC is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "a major KFC supplier". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
KFC
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Legal Impact for Chickens (LIC) is so grateful to ACX for launching us, and to all the ACX readers who have supported us! Thus far, LIC has filed four lawsuits: (1) Smith v. Vachris, the shareholder derivative case against Costco’s executives for chicken neglect, which was mentioned in The Washington Post, Fox Business, CNN Business, Meatingplace, and a viral TikTok. (2) LIC v. Case Farms, a cruelty suit against a major KFC supplier, which is currently pending before the North Carolina Court of Appeals. (3) Animal Outlook v. Harvey’s Market, which successfully stopped a DC butcher shop from selling foie gras. And (4) LIC v. Alexandre, a cruelty suit against an abusive dairy, which is currently pending before a California court. LIC has also sponsored an undercover investigation of poultry-giant Foster Farms, leading to a currently ongoing sheriff’s-office investigation. LIC got a California caterer to drop foie gras with a simple cease-and-desist letter. And LIC established a new potential avenue to create consequences for animal abuse: through an amicus brief at sentencing for the violation of another law. LIC also received a recommendation from Animal Charity Evaluators!
Kia

Kia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2021 and June 28, 2021. The archive places it in contexts such as "government had offered protection and subsidies to... three putative makers of 'citizens' cars: HMC, Shinjin, and Kia". It most often appears alongside Alexander Hamilton, America, ASEAN.

Reference entry
Kia
Mention count
1
Issue count
1
First seen
June 28, 2021
Last seen
June 28, 2021
June 28, 2021 · Original source
No direct inline source block was recovered for this mention.
Kickstarter

Kickstarter is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 12, 2023 and December 12, 2023. The archive places it in contexts such as "marketplace as a sort of Kickstarter, where everyone who hates a certain politician can add more money to the pot". It most often appears alongside 2024, Aaron Peskin, accelerationist conspiracy.

Reference entry
Kickstarter
Mention count
1
Issue count
1
First seen
December 12, 2023
Last seen
December 12, 2023
December 12, 2023 · Original source
“Of course, there’s a coordination problem. Peskin doesn’t want to advertise that he’ll drop out for $500,000, because then his constituents will know he’s mercenary, and people can just wait for him to lose instead of paying. What you need is for buyers to publicly post their bid, and then Peskin can accept in one click. I’m imagining the marketplace as a sort of Kickstarter, where everyone who hates a certain politician can add more money to the pot, and politicians can go on, see how much is in their pot, and accept once it gets big enough.”
Kindle

Kindle is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 28, 2023 and July 28, 2023. The archive places it in contexts such as "has the advantage of being available on Kindle"; "which has the advantage of being available on Kindle". It most often appears alongside 1923 Hyperinflation, Adolf Hitler, All hope abandon, ye who enter here.

Reference entry
Kindle
Mention count
1
Issue count
1
First seen
July 28, 2023
Last seen
July 28, 2023
July 28, 2023 · Original source
His emotional range spans only from a kind of tired nostalgia to the reckless joy of intoxication, punctuated by his most prized feeling by far, the gleefully murderous “bloodthirst” of mortal combat. So everyone who had read some Jünger, which at the time of publication would likely include most of the German population and definitely most of the Nazis, could see right through the facade of fiction. It is an obvious conceit that made the book just barely publishable, in a time and place where saying outright that the Nazis were disgusting savages would have gotten everyone involved a headshot. After 1945, Jünger did admit that the book was (also) a commentary on the political reality of its time. And that he knew perfectly well that in publishing this “fiction” he was playing with his life. And still he got it published, uncensored, in Germany in 1939, just before Hitler started the second World War. Today the most widely accepted history of the subject is that Jünger was only saved from a grisly fate by the personal intervention of Hitler himself, who loved “Storm of Steel” and presumably wouldn't have liked to admit that his favorite author utterly despised him. And it would have been very tempting to just not admit that, because before the Nazis came to power, Jünger had sympathized with them, although he never counted himself among them. Hitler had sent Jünger fan letters; the responses have unfortunately been lost. Jünger’s many political rants in the 1920s do contain several explicit endorsements of the strength of the Nazis and of their value as allies to Jünger’s vague and contradictory nationalist cause. By the time he wrote the Marble Cliffs, he had stopped endorsing them. But this history made it easy for the Nazis to publicly pretend he had just written a fictional novella, or maybe he was talking about Bolshevism or something, but surely he didn’t mean them. It was an Emperor’s New Clothes situation, where nobody dared to say out loud what everyone could see. Although additional reprints were verboten in 1942, the excuse of a lack of paper due to the war was perfectly plausible and didn’t betray the discomfort with the content that nevertheless is well-documented to have been present among the Nazi ranks. All of that is to say we can safely dispense with the charade entirely and accept that this book is about the Nazis. It makes general points on the nature and fate of tyranny that do apply to Bolshevism, but the Nazis are the immediate and obvious instance of tyranny to which this book clearly reacts. And it is written by someone who had walked among the Nazis, had previously been friends with some of them, exchanged letters with many of the best-informed men especially in the military, and was perceptive enough for his opinions to deserve much of the confidence he states them with. Besides this conceit, the other concession to the political realities Jünger makes is that the book makes no mention of Jews. The world he is describing is fictional, but it is an amalgamation of European cultures that all had some Jews, so this absence is conspicuous. Obviously Jünger couldn't possibly have seen this book published if it depicted Jews in any way that wasn’t extremely negative. I guess he was unwilling to do that. In the 1920s, Jünger had ranted against “globalist” liberal Jews several times, and once even argued that one couldn't be both a Jew and a German. But he saw nothing wrong with being an orthodox Jew, openly admired Zionism, expressed in letters complete revulsion with Nazi antisemitism and had even publicly spoken out against the pseudoscientific racial theories of the Nazis. After writing this book, when serving as an officer again in France, Jünger went on to save a couple of French Jews from deportation and death, at moderate risk to his own life. Later he’d discuss the Kabbalah with Gershom Sholem, the brother of his childhood friend Werner Sholem. For these reasons, I imagine he did not see Jews negatively enough for the Nazis, and was too uncompromising to pretend that even his narrator did. I think this dilemma fully explains why there are no Jews in this book. In 1935, when Winston Churchill for example still publicly admired “the courage, the perseverance, and the vital force” of Adolf Hitler, Jünger claims to have already understood the bottomlessness of Hitler's depravity by noticing he was using the word “Vernichtung” (annihilation) way too much. He was remarkably right, years before most could see it, but even more remarkably his method of understanding was a poet's acute sense of word choice! And from then, even though he agreed with nationalist dictatorship as a goal and method, he distanced himself from National Socialism because he was disgusted with the vile character of the leader of this particular nationalist dictatorship. If that doesn't show you the peculiar kind of man Ernst Jünger was, I don't know what to tell you. The craft and the poetry You all know the wild grief that besets us when we remember times of happiness. How far beyond recall they are, and we are severed from them by something more pitiless than leagues and miles. The “marble cliffs” in the title of this short novella unite senses of beauty, majesty and danger, which is programmatic for this entire book. It begins with a visionary description of life in the traditional society of “the Marina” in an overwhelmingly beautiful state of paradise. The narrator lives on the edge of this society in a “hermitage” with his brother, his housekeeper and his son. The latter has a strange power over the local population of poisonous snakes. This opening act is without question the most elaborate celebration of poetic beauty I have ever read. Superficially it could be dismissed as purple prose. But due to Jünger’s clever use of poetic techniques in what at first appears to be prose text, there’s a rhythm, a density and a lucidity to it that makes it pretty much a very long poem, and gives it an intoxicating quality which is most apparent when you read it out loud. In the autumn we feasted like sages and did honour to the exquisite wines in which the southern slopes of the Marina abound. When in the vineyards between red foliage and dark grape clusters we caught the jocund calls of the vintagers, when in the little towns and villages the wine-presses began to creak, and the odour of the pressed grape skins drew its heady veils round the farms, we would go down to the innkeepers, coopers and wine-growers, and drink with them from the full-bellied jug. And there we would always meet with gay companions, for the land is rich and fair, so that in it flourishes untroubled leisure, and wit and humour are its unquestioned coin. I know this works, because I did an experiment. I read this book aloud, to a room full of people who were smoking pot. The book is short and the plan was to read all of it over the evening. I have read to pot smokers occasionally, but with this book it was different. They were enjoying it very much for the first couple of chapters, and exclaimed many times it was “perfect” for pot. But some hours, chapters and joints in, when the narrator goes on an expedition into a fantastically beautiful forest, they were so utterly overwhelmed by the intensity of the descriptions of nature they asked me to stop. I and the only other sober person in the room were the only ones who were willing to continue. We all had very intense dreams that night. Once we had broken through the thick hedge of dogwood and blackthorn we entered the high forest, territory where the blow of an axe had never resounded. The ancient trunks, the pride of the Chief Ranger, stood gleaming damp like pillars with their capitals hidden by the mist. We walked among them as if through a spacious hall, and, like the magic setting of a stage, festoons of ivy and clematis blooms hung down towards us out of the void. The ground was piled high with mould and rotting branches, in the bark of which fiery red mushrooms had sprung up, so that we felt for a moment like divers wandering among coral gardens. Wherever one of the mighty trunks had fallen from age or struck by lightning, we stepped out on to a little clearing on which the yellow foxglove grew in thick clumps. On the rotting ground the deadly nightshade bloomed in profusion; on its stalk the dark purple calices shook like funeral bells. It comes as no surprise that Jünger had much practice writing that way, from putting into his diaries a lot of his dreams and his numerous drug experiences. Jünger had long been inclined to deeply poetic descriptions of the real events he described, but this intensity at this length is genuinely new to his writing. Wherever he can use plurals he prefers them over the singular, wherever he can use more melodic and beautiful verbs (like when the characters “step out on” rather than “walk into” clearings) he does. Maybe the pretense of the narrator not being himself allowed Jünger to wallow in his characteristic aestheticism, take it to an extreme and arguably to the point of self-parody. Skip to the next heading if you don’t care about translation The extreme language of this book made me doubt there would be any translation into English that could do it justice. After all, if you throw this last excerpt into DeepL you get: After breaking through a dense fringe of blackthorn and cornets, we entered the high forest, in the grounds of which the blow of the axe had never sounded. The old trunks, which formed the pride of the head forester, stood in the damp glow like columns whose capitals were hidden by the haze. We walked among them as through wide vestibules, and like the magic work on a stage, ivy vines and clematis blossoms hung down on us from the invisible. The ground was covered high with mulm and decaying branches on whose bark mushrooms, burning red cup fungi, had settled, so that a feeling of divers walking through coral gardens crept over us. Where one of these giant trunks was tossed by age or lightning, we stepped out into small clearings where yellow foxglove stood in dense clumps. Belladonna bushes also proliferated on the rotten ground, on whose branches the flower calyxes in brown violet swayed like death bells. It’s still pretty, and it works on a matter-of-fact level. None of it is just wrong. But can you see how it has a lot less of the dreamlike quality? A “fringe” is a geographical feature, while the “hedge” emphasizes its role as an obstacle in a journey. Those “old” trunks are less poetic than “ancient” ones. A “head forester” is a job description, while a “Chief Ranger” is a seminal figure. The “vestibules” are a literal translation of the original, but the English word is used a lot less than German “Vestibüle” was back then. So that’s a word you may need to work to understand, which gets you out of the story’s flow, so “spacious hall” is better. There are even more such nitpicks to be made even in this short paragraph, but my point is these difficulties pervade every single paragraph of the book. ChatGPT very similarly fails to overcome them. Since January, there is a new translation by Tess Lewis, which has the advantage of being available on Kindle. I’ll spare you another repeat of the same paragraph and just say I think DeepL did most of this translation. But Tess Lewis did improve on many of its word choices and I’ll grudgingly concede this translation is good enough. It still sounds too modern for me, too much like prose and too little like poetry. Therefore, all previous and following excerpts are from the Stuart Hood translation, published in 1947, which I was astonished to find does pull it off! Let me assure anyone who doesn’t speak German, or doesn’t study translation, that this one is absolutely exemplary and surely represents years of painstaking work. Stuart Hood was a Scot who knew German very well. Like Jünger he was a veteran officer, and he needed German for his intelligence missions in World War 2. This is his very first published translation of an entire book. It harnesses a considerable talent, which is also evidenced by how Stuart Hood went on to become an accomplished writer himself, a BBC executive, a professor and several other notable things. And it is clearly a labor of intense love — right after the war, while working on it, Hood corresponded with Jünger and even went to visit him at least twice and they talked at length about the art of translation and how to translate specific points of the Marble Cliffs. The end of this last quote, “on its stalk the dark purple calices shook like funeral bells.” exemplifies how precisely Hood has understood Jünger. Why “calices”, not “chalices”? Because that is the old-fashioned form of this word, and using it is unnecessarily peculiar, but it doesn’t make you stop and look into a dictionary. It isn’t even more precise than DeepL’s and ChatGPT’s and Tess Lewis’s “calyxes” for the word “Blumenkelche” in the Original. But it captures precisely how the author was using his German language. This is because on every page of the original, there are choices of individual words that evoke subtleties of mood and allusion that are strictly impossible to translate, because English doesn’t have a similar-enough group of synonyms from which to make the equivalent choice. Some of that must inevitably get lost in translation. But these “calices” are an example of how Hood has the audacity to frequently insert his own new peculiar word choices — which restore exactly the same effect! It might take entire months until AI can do that! Unfortunately the New Directions edition with this translation has been out of print for a while, although I heard from a regrettably less law-abiding friend that the PDF is easy to find. But a few years ago someone bought the UK rights to this translation and republished it. While this edition has several uncorrected OCR mistakes, one of which horrifyingly turns “Flayer’s Copse” into “Player’s Copse”, at least this makes the better translation available (legally) again. What actually happens (spoilers) After six chapters of descriptions of paradise, and of the botanical work the brothers do since they don’t need to make a living, the book continues with a gradual decline of this gorgeous world. This again is much more of a richly detailed description than a story plot. It begins with the introduction of the Chief Ranger. The brothers know him from their military community, from before his takeover begins. There is some debate about whether the Chief Ranger stands for Hitler, Stalin or Hermann Göring. I think this debate is misguided. The character of the Chief Ranger, the antagonist of the narrator and all he holds dear, is never named but only ever referred to by his title. He does not appear to have staff or lieutenants at all, nor any personal history. And Jünger is profoundly uninterested in the personalities of all his characters beneath what they pay attention to (except the narrator’s brother) so even this important figure is roughly sketched at best. Therefore, I believe he is best understood as more of an archetype or role, The Tyrant, denuded of the individual traits or histories that make one tyrant a Führer, another a General Secretary and yet another a Great Leader. So, what makes a tyrant? According to Jünger, “wherever free spirits establish their sway these primeval powers will always join their company like a snake creeping to an open fire. They are the old connoisseurs of power who see a new day dawning in which to reestablish the tyranny that has lived in their hearts since the beginning of time.” The Chief Ranger is also “a master of feigning frankness that was full of snares for the unwary.” He has a reputation for wealth and a strong visual brand (a gold-embroidered green coat) that makes sure he always leaves “an imprint on one’s memory”. He exudes a “breath of primitive power” and has a strong charisma that gives an impression of “both cunning and unshakable power — yes, at times even majesty.” As he begins to usurp power, “reports spread from mouth to mouth of infringements of the law and of acts of violence in the neighbourhood, and finally such incidents occurred publicly and with no attempt to concealment. A cloud of fear preceded the Chief Ranger like the mountain mist that presages the storm. Fear enveloped him, and I am convinced that therein far more than in his own person lay his power.” From what I know about tyrants, that sounds about right. For the next seven chapters, the vile followers of the Chief Ranger continually corrupt everything. The sophisticated culture of the Marina is surrounded by the rough herdsmen clans of the surrounding Campagna steppe, beyond which lies the Chief Ranger’s forest populated by lowlifes. The class metaphor is blindingly obvious, and Jünger’s theory of how these lowlifes overcome first the Campagna and then the Marina is not subtle either. After the Alta Plana war, and the defeat, the entire society has been weakened. “Thus in exhausted bodies corruption will set in by way of wounds which a sound man would scarcely notice. The first symptoms, therefore, were not recognized.” Very gradually, law gives way to lawlessness, spreading from and with the lower classes foresters in many different ways. Violent crime grows, in descriptions very reminiscent of the many deadly street fights of the late Weimar republic. Various elements of traditional culture become corrupted. Those who would defend it are intimidated and attacked. The constitutional lawful reaction is too slow, so by the time it manages to convene and have democratic debates, it is already infiltrated. And there’s one paragraph worth quoting in full. Herein, above all, lay a masterly trait of the Chief Ranger. He administered fear in small doses which he gradually increased, and which aimed at crippling resistance. The role he played in the disorders which were so finely spun in the heart of his woods was that of a power for order; for while his agents of lower rank, who had established themselves in the clans, fostered anarchy, the initiated penetrated into the civic offices and the magistracy, and there won the reputation of men of deeds who would bring the mob to its senses. Thus the Chief Ranger was like an evil doctor who first encourages the disease so that he may practise on the sufferer the surgery he has in mind. Today this is a mainstream view in German history. In 1939, it could have been prosecuted as high treason and punished with death. On the backdrop of ever escalating mayhem, two old men who are friends of the brothers are described: Belovar, a clan patriarch from the Campagna, and Father Lampros, an eminent Christian monk. In very different ways, they both are very helpful, each both in the botanical work and against the mounting threat. The brothers decide against meeting the violence with violence, delve deeper into their work, become increasingly pessimistic and develop a hope that they can rescue the results of their work into an imperishable afterlife by burning it with an ancient mystical crystal lens that they somehow inherited. The narrator describes continued excursions for rare plants, through the country that is becoming increasingly treacherous and foreboding, until finally, well after the middle point of the book, with one particular excursion for an extremely rare flower, the actual continual story begins. Today we look at the Nazis with horror, but Jünger has dug too many trenches into hills of rotting corpses to be easily horrified. Instead of horror, his feelings towards the Nazis are mostly contempt, seasoned with disgust, and that has been pervading his description of the rise of the Chief Ranger’s henchmen over the last couple of chapters. But he does give one instance of pure horror and it is here, in the very heart of the book, when the two brothers on their excursion happen to discover, in the ill-reputed area of Flayer's Copse, the Chief Ranger’s remote “flaying-hut” of Koppels-Bleek. The original Köppels-Bleek is a German wordplay, about as subtle as a drone base in a sci-fi novel that happens to be called Obamazliez. Koppels-Bleek is where the Chief Ranger has his enemies tortured to death. It has frequently been called a concentration camp, but that is imprecise. It is really a Vernichtungslager, a death camp, which unlike a “normal” concentration camp is built for the express purpose that no torture victim ever gets out alive. This is a prediction, because while Nazi concentration camps were set up starting in 1933, Vernichtungslager were only built three years after the “Marble Cliffs” were published. After an intensely gruesome description of the particulars of this place, the narrator assesses its importance as follows. Such are the dungeons above which rise the proud castles of the tyrants, and from them is to be seen rising the curling savoury smoke of their banquets. They are terrible noisome pits in which a God-forsaken crew revels to all eternity in the degradation of human dignity and human freedom. He is so certain he has captured the very essence of tyranny, “the abode of tyranny in all its shame”, that he puts this climax at the two thirds mark of the book and makes it exceedingly obvious this is where the third and final act begins, as the pace of the book changes entirely. Although the narrator still includes some retrospectives, he is now finally telling a real story. Strikingly, the brothers return to botany — remember this, it will be important later — and then to their home, where they soon get two conspiring visitors. Braquemart is a competent, racist, nihilistic fellow veteran. The narrator despises him at length for his heartless theory-mindedness. Prince Smyrna is new, young, seems to the narrator to know “the nature of justice and order” but is too weak and inexperienced to shoulder the responsibility he is heroically taking on. The two visitors want to Do Something about the Chief Ranger — what exactly is never said, though a personal confrontation or assassination is implied. They leave for the Chief Ranger's territory. This entire chapter feels very much like a comment on some political acquaintances of Jünger who attempted to challenge the Nazis, and failed. The next day, Father Lampros gives the narrator a mission to arm himself and look for these two men. He goes to old Belovar's farmstead, where he learns of commotion in the direction of Flayer's Copse, and the old clan patriarch goes to war. Before, the book was a dreamy soliloquy; now we see dramatic wartime action. Ernst Jünger has had a lot of practice with writing about that kind of thing, and it shows. Their small but experienced war party with a lot of dogs goes towards Koppels-Bleek and is soon met with two confused, horrific, riveting battles. The narrator stumbles through and finds at Koppels-Bleek the heads of Prince Smyrna and Braquemart. The former strikes him as a symbol of how nobility remains real, and he picks it up. With it, he retreats through mayhem and danger into the complete flaming destruction of the Marina. He marvels at the beauty of the flames — remember this too, it will also be important later — and, with his hunters in hot pursuit, runs to his house. There his son uses his strange power over the local population of poisonous snakes to make them defeat the nearest attackers. The brothers burn down the house, go find Father Lampros and see him die. From an old soldier comrade who owes them a favor they get room on a ship to flee across the water to Alta Plana, where an old enemy who owes them another favor takes them in. There’s an implicit framing story of how the narrator lives to tell the tale of these memories to some unspecified audience, and as it ends it mentions in passing that sometime after these events, a new cathedral has been built on the ruins of the Marina and the head of Prince Smyrna went there as a relic. This small bit still stands out today, and would have stood out even more starkly to contemporary readers, because in the context of everything that happened before, this bit publicly, extremely boldly, and correctly, predicts the eventual fate of the Nazis. Not once in this entire story has the narrator expressed surprise at this progression of events, or given any other indication it is in any way unlikely. The narrator, and the author through him, seems to be saying this is just the way it goes with tyranny, when a society has lost too much of its strength to fight off the bestial attacks of the lowly. I have omitted not just many smaller elements of the story but also a huge number of allusions to ancient history, (German) literature and especially the Bible. I imagine Jünger put them there as prizes for the few who would find them. This is one of the ways that I think On the Marble Cliffs is Ernst Jünger’s Unsong: a vehicle that lets a prolific nonfiction author
Klonopin

Klonopin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "benzodiazepines, a popular class of psychiatric medication including ... Klonopin (clonazepam)". It most often appears alongside alcohol, allopregnanolone, allopregnanolone.

Reference entry
Klonopin
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator! (or maybe that’s just an urban legend, I’ve never found proof either way) The discovery of endorphins (ie endogenous opiates) helped shed light on the brain’s reward system. So the discovery of a sort of endogenous benzodiazepine was pretty exciting. Maybe it’s some kind of master control switch for anxiety or something? Psychiatrists only know two ways to respond to an exciting new thing: publishing breathless studies claiming that it’s the true mechanism of action for SSRIs, and publishing breathless studies claiming that it’s the true biological basis of depression. This time, they did both: see eg Fluoxetine elevates allopregnanolone levels in female rat brain and The role of allopregnanolone in depressive-like behaviors. The basic theory was that stress / social isolation / etc → decreased allopregnanolone → something something BDNF and synaptogenesis → depression. And SSRIs → increased allopregnanolone → something something BDNF and synpatogenesis → recovery! Change the word “allopregnanolone”, and that’s every theory in psychiatry. But this particular theory had two extra pieces of evidence: premenstrual dysphoric disorder and postpartum depression. Remember, allopregananolone is a natural metabolite of the female hormone progesterone. Progesterone levels go up during pregnancy and the ~18th day of the menstrual cycle, then crash back down after delivery and the ~24th day of the menstrual cycle. Meanwhile, some women get depressed after delivering a baby, or on the ~24th day of their menstrual cycle. Suspicious! Maybe it’s because their progesterone was getting converted into allopregnanolone, an antidepressant hormone that affects mood! (why doesn’t every woman get PPD and PMDD? This study suggests that women with PMDD have altered sensitivity to allopregnanolone; plausibly people with PPD have some other form of altered sensitivity. In case you have the same question I do: the correlation between PMDD and PPD is not 100% but still pretty significant) History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Kool-Aid

Kool-Aid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2022 and June 23, 2022. The archive places it in contexts such as "killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid". It most often appears alongside 1978, 2016 essay, A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs.

Reference entry
Kool-Aid
Mention count
1
Issue count
1
First seen
June 23, 2022
Last seen
June 23, 2022
June 23, 2022 · Original source
For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
KRKA-Pharma

KRKA-Pharma is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "gotten money from KRKA-Pharma". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
KRKA-Pharma
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Kumu

Kumu is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Think Airtable+Vensim+Roam+Kumu". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Kumu
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#6: System Dynamics Simulator I'm Oleksandr Nikitin, and I want to build a system dynamics simulator. Enable independent researchers to simulate, forecast, and visualize metabolic pathways, epidemic spread, mass transit, ecology, macroeconomics, etc. Show, don't tell. Without code. Think Airtable+Vensim+Roam+Kumu, integrated and working offline. Why offline? Why simulate? Why a new tool? Complex systems must be simulated. You miss emergent phenomena if you analyze parts separately or simplify the details. Offline sets you free from distractions and groupthink. Free to make your own breakthroughs. Take your references, notes and data with you, dive deep, then return with the verified, reproducible, interactive model. Research can take years. Tools should outlast devices and app stores. And it must be fast. Isn’t it insane for a productivity tool to make you wait? I spent years on prototypes and algorithms, tested in companies since 2013, and now I want to put these experiments together. Not as a startup. As a tool accessible to everyone. The plan: create a community of curious inquisitive makers, empower them with a small fast and robust core app, iterate and grow together, augment the human intelligence even more, and understand the world. I seek funding to focus on this project full-time, for two years. To launch and to guide people to the finished research. Sounds inspiring? Worth the money? Want more details? Ping me at oleksandr@tvori.info. Also see https://cortex.substack.com/
Kılıç

Kılıç is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "Kılıç published its first sustainability report detailing fish welfare policies". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
Kılıç
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
l-methylfolate

l-methylfolate is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "The most-studied and best-supported supplements for depression is l-methylfolate"; "Start taking l-methylfolate 15 mg daily". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
l-methylfolate
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
The short version: Depression has a combination of biological, psychological, and social causes. You can address the social causes by changing your life circumstances (and research suggests people underestimate the potential benefits of making major life changes). You can address the psychological causes with therapy; possible therapies are diverse and complicated but I especially recommend “behavioral activation” therapy (where you try to keep a schedule and also do new, interesting things) and David Burns’ book Feeling Good. You can address the biological causes with a combination of lifestyle changes, medications, and supplements. Consider exercising more and adapting a modified Mediterranean diet. Consider taking antidepressants like escitalopram and bupropion, and supplements like l-methylfolate. Other non-chemical biological options include light therapy (safe and easy), transcranial magnetic stimulation (more complicated), and electroconvulsive therapy (difficult but extremely effective last-ditch solution). If something treats your depression, continue it for some length of time depending on the type of intervention, then consider withdrawing it to see if you can maintain your mood without it.
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
L-methylfolate is a form of folic acid, aka Vitamin B9, common in various vegetables. It’s part of various important chemical processes in the body, including the synthesis of serotonin, and various studies support its use in depression. Some people will try to claim that a gene called MTHFR is very relevant here, but I disagree with this and will have a page up about it eventually – the summary is that you should consider using l-methylfolate regardless of what allele of MTHFR you have. I’ve listed this supplement first because it’s the only one which has been officially approved by the FDA as safe and effective for depression. The FDA-approved version is called Deplin, and is prescription-only and more expensive, but it’s chemically identical to regular l-methylfolate which you can buy without a prescription in stores. Be careful as many stores will sell 1 mg tablets, but the recommended dose is 7.5 – 15 mg daily. You can get l-methylfolate 15 mg here.
L.L. Bean

L.L. Bean is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 24, 2021 and February 24, 2021. The archive places it in contexts such as "They buy their clothes from L.L. Bean and Land's End". It most often appears alongside 1950s, 1980s, 1983.

Reference entry
L.L. Bean
Mention count
1
Issue count
1
First seen
February 24, 2021
Last seen
February 24, 2021
February 24, 2021 · Original source
Although you wouldn't expect them to have any consistent aesthetic, Fussell gets weirdly specific about them. They buy their clothes from L.L. Bean and Land's End, and tend to dress in down vests, flannel shirts, and hiking boots (which apparently "conveys the message [that] I am freer and less terrified than you are"). They enjoy touch football (because it is actually fun, unlike other sports which are just class signaling), and carry their infants around in slings or papooses (because these are the objectively simplest ways to convey infants). They read British, French, and Italian periodicals (because this is objectively the best way to keep abreast of world affairs), and live in cute old houses in unusual locations. Their front yard may be gravel (because they have transcended the class signaling of lawns), and their furniture includes "parody displays" like "an elephant's foot umbrella stand" and "campy fabric". "Instead of the chart of Nantucket or Catalina Island favored by the upper-middles, a chart of Bikini Atoll or Guadalcanal. On the coffee table, Mother Jones and The Bulletin of the Atomic Scientists." Their TV preferences are for "classic reruns like The Honeymooners or I Love Lucy" (apparently the objectively best TV shows).
LA Lakers

LA Lakers is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 29, 2025 and August 29, 2025. The archive places it in contexts such as "I will be wearing a red shirt and a LA Lakers cap". It most often appears alongside "Beer Capital" pub, 100 Black Birch Trail, 11841 Wagner Street, Culver City.

Reference entry
LA Lakers
Mention count
1
Issue count
1
First seen
August 29, 2025
Last seen
August 29, 2025
August 29, 2025 · Original source
Contact: Mihai Contact Info: mihai[period]truta1996[a t]gmail[period]com Time: Saturday, September 6th, 2:00 PM Location: In front of the National History Museum of Romania, I will be wearing a red shirt and a LA Lakers cap, will hold a sign saying "ACX Meetup". Coordinates: https://plus.codes/8GP8C3JW+MR Notes: To contact me twitter DMs are open (mihai_truta3)
Lalio

Lalio is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as "younger kids use ... Lalio". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Lalio
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
Reading (Older kids are on “Alpha Reads”; younger kids use Amira and Lalio)
Land's End

Land's End is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 24, 2021 and February 24, 2021. The archive places it in contexts such as "They buy their clothes from L.L. Bean and Land's End". It most often appears alongside 1950s, 1980s, 1983.

Reference entry
Land's End
Mention count
1
Issue count
1
First seen
February 24, 2021
Last seen
February 24, 2021
February 24, 2021 · Original source
Although you wouldn't expect them to have any consistent aesthetic, Fussell gets weirdly specific about them. They buy their clothes from L.L. Bean and Land's End, and tend to dress in down vests, flannel shirts, and hiking boots (which apparently "conveys the message [that] I am freer and less terrified than you are"). They enjoy touch football (because it is actually fun, unlike other sports which are just class signaling), and carry their infants around in slings or papooses (because these are the objectively simplest ways to convey infants). They read British, French, and Italian periodicals (because this is objectively the best way to keep abreast of world affairs), and live in cute old houses in unusual locations. Their front yard may be gravel (because they have transcended the class signaling of lawns), and their furniture includes "parody displays" like "an elephant's foot umbrella stand" and "campy fabric". "Instead of the chart of Nantucket or Catalina Island favored by the upper-middles, a chart of Bikini Atoll or Guadalcanal. On the coffee table, Mother Jones and The Bulletin of the Atomic Scientists." Their TV preferences are for "classic reruns like The Honeymooners or I Love Lucy" (apparently the objectively best TV shows).
Lantern

Lantern is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 07, 2023 and December 07, 2023. The archive places it in contexts such as "Can’t people transfer the bacterium among themselves without paying Lantern?". It most often appears alongside Aaron, Aaron Silverbook, Aella.

Reference entry
Lantern
Mention count
1
Issue count
1
First seen
December 07, 2023
Last seen
December 07, 2023
December 07, 2023 · Original source
Lantern Bioworks says they have a cure for tooth decay. Their product is a genetically modified bacterium which infects your mouth, outcompetes all the tooth-decay-causing bacteria, and doesn’t cause tooth decay itself. If it works, it could make cavities a thing of the past (you should still brush for backup and cosmetic reasons).
I talked to Lantern founder Aaron Silverbook to get an idea of how this works, both in a biological and an economic sense. Aaron was very knowledgeable and forthcoming, although he uses the phrase “YOLO” somewhat more often than most biotech founders. This post isn’t a verbatim interview transcript, just a writeup of what I learned based on his answers.
[Conflict of interest notice: Lantern is mostly rationalists and includes some friends. My wife consulted for them early on. They offered my wife and me free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating. Consider this an attempt to spotlight interesting work that people I like are doing, not a hard-hitting investigation.]
Lantus

Lantus is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "Humira and Lantus are good examples of drugs"; "Humira and Lantus are good examples of drugs which would be significantly cheaper by now". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Lantus
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I would be surprised if Semaglutide was cheaply available as a generic by the mid-2030s unless there are significant reforms made to the patent system or pharma industry rules. Humira and Lantus are good examples of drugs which would be significantly cheaper by now except for repeated patent extension and industry deals maintaining monopolies (although hopefully coming down soon).
laser

laser is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 06, 2024 and August 06, 2024. The archive places it in contexts such as "and produced... the laser". It most often appears alongside AI, altruism, America.

Reference entry
laser
Mention count
1
Issue count
1
First seen
August 06, 2024
Last seen
August 06, 2024
August 06, 2024 · Original source
I’m skeptical of this argument. America’s been at peace since World War II (foreign adventures like Vietnam haven’t substantially changed our national experience) and produced the computing revolution, the Internet, AI, the moon landing, the Human Genome Project, antiretrovirals, the microwave, the laser, the smartphone, and the reusable rocket. During that time, Iraq has had approximately eight major wars and didn’t even get a cuckoo clock out of it.
Lavender

Lavender is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "Lavender/Silexan Has Been Astounding and Highly Recommend Silexan Lavender For Anxiety". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
Lavender
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
But recently silexan (derived from lavender) has started to stand out of the crowd. Daily Mail had an interview with psychiatry professor Hans-Peter Volz, who said that silexan should be first-line for anxiety, replacing things like SSRIs and Xanax. And a very reputable professional publication within psychiatry, The Carlat Report, published an article and a podcast touting silexan:
Silexan is a branded extract of lavender oil created by Wilmar Schwabe GmbH, a German pharma company. Nobody is sure about the mechanism of action, but it probably involves serotonin 1A receptors, the same receptors blocked by mediocre anti-anxiety medication buspirone and some of the newer antidepressants.
So fine, let’s look at the studies. A typical example is Kaspar (2014), Lavender oil preparation Silexan is effective in generalized anxiety disorder. It has 539 people, which is really quite impressive - usually these kinds of supplement trials would have more like 10% of that. The study is double-blind (patients don’t know if they’re getting silexan or placebo, and doctors don’t know which one they’re giving) and they made sure the placebo capsules smelled like lavender (a nice touch!) The groups were randomized carefully, but there were some statistically significant random differences between them; none of them seemed too worrying to me but your opinion might differ. There was a clear, obvious, and dose-dependent effect of silexan vs. placebo (p < 0.001) on seven of eight outcomes measured; the eighth was “physical health” and it’s fine if an anxiety drug doesn’t help with this (although you could always hope it would relieve some ailments by making people less stressed). It did significantly better than paroxetine, which only reached statistically significant effect size on about half of the outcomes (par for the course in these kinds of studies, SSRIs are kind of weak). Effect size was 0.37 for the 80 mg dose, and 0.5 for the 160 mg dose.
lecanemab

lecanemab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "epitope more like lecanemab’s, and given in the preclinical disease stage"; "Lecanemab in its phase 2b and phase 3"; "similar to lecanemab or donanemab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
lecanemab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
I am not claiming that the disease is “as simple as” amyloid deposits directly inducing neurodegeneration. As described above, they act indirectly, via the eventual downstream tau pathology, and possibly an associated microglial/astrocytic inflammatory response. Therefore, there are many people in the preclinical, amyloid-only disease phase who will eventually progress to dementia but have not yet. These two clarifications imply that even though amyloid pathology is a necessary and (in enough severity) sufficient cause of the disease under normal circumstances, therapies with other targets might still be effective, either intervening upstream such that amyloid deposits never occur, or downstream so as to prevent the neurodegenerative process. The testable prediction I would bet on the following: A therapy whose sole intended mechanism involves amyloid production or clearance, in a randomized, double-blind, placebo-controlled trial, will, in the next 12 years, achieve a slowdown of cognitive decline of at least 75%, with a p-value below 0.001, in its preregistered primary cognitive endpoint (or an average of all such endpoints if more than one exists). I’d eventually expect better than 75% efficacy, but getting stuff to work takes time, and I wanted to make a prediction which can be tested in a reasonable timeframe. On the other hand, if a clinical trial completes earlier than 12 years from now (perhaps [73], reading out in 2027), sustains extremely good amyloid clearance at the preclinical stage, and has a good safety profile, but doesn’t make substantial progress towards this 75% goal, then I would consider this prediction refuted in advance. For targeting amyloid, I’m most optimistic about a blood brain barrier (BBB)-penetrating antibody such as trontinemab [74–76], but with an epitope more like lecanemab’s, and given in the preclinical disease stage. Other options for targeting amyloid include antisense oligonucleotides for APP as well as γ-secretase modulators. The successes and failures of amyloid antibodies There have now been three amyloid antibodies with positive phase 3 (and earlier) clinical trials on cognitive endpoints (but with much less than 75% efficacy): Aducanumab in phase 1b [77] (19% on my average across cognitive endpoints for the highest two doses) and one of two phase 3 trials [78] (22%, but negative 2% in the other trial, which also gave a lower dose on average).
Lecanemab in its phase 2b [79] (30% on the primary measure, though it technically failed because of its ambitious Bayesian endpoint) and phase 3 [80] (27%).
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
LEF

LEF is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "price per dose to the same as Jarrow and LEF". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
LEF
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
So anyway, that's the situation. To say I am frustrated doesn't even scratch the surface. However, I can only fight so many fights at once. Even so, we were able to add a 540ct bottle that gets the price per dose to the same as Jarrow and LEF, while still complying with the TMLA and MAP agreements. Ours will also always have what we claim.
LEGALIZE HOUSING

LEGALIZE HOUSING is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 04, 2023 and January 04, 2023. The archive places it in contexts such as "based on his LEGALIZE HOUSING t-shirt". It most often appears alongside AI Circle, Anthropic, Asana.

Reference entry
LEGALIZE HOUSING
Mention count
1
Issue count
1
First seen
January 04, 2023
Last seen
January 04, 2023
January 04, 2023 · Original source
“Yeah, California has great weather,” says one of the guys in the kitchen; based on his LEGALIZE HOUSING t-shirt, you infer he is the YIMBY. “Which makes it even crazier that 80,000 Californians a year move to Texas, which is 100 degrees plus in summer and below freezing in winter. It’s not because they like the weather, it’s because California’s restrictive housing policies make it impossible to live here, and despite everything else Texas gets wrong at least you can build homes there!”
LEGALIZE HOUSING t-shirt

LEGALIZE HOUSING t-shirt is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 04, 2023 and January 04, 2023. The archive places it in contexts such as "based on his LEGALIZE HOUSING t-shirt". It most often appears alongside AI Circle, Anthropic, Asana.

Mention count
1
Issue count
1
First seen
January 04, 2023
Last seen
January 04, 2023
January 04, 2023 · Original source
“Yeah, California has great weather,” says one of the guys in the kitchen; based on his LEGALIZE HOUSING t-shirt, you infer he is the YIMBY. “Which makes it even crazier that 80,000 Californians a year move to Texas, which is 100 degrees plus in summer and below freezing in winter. It’s not because they like the weather, it’s because California’s restrictive housing policies make it impossible to live here, and despite everything else Texas gets wrong at least you can build homes there!”
Lego

Lego is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2023 and September 19, 2023. The archive places it in contexts such as "the Batsub, only $39.99 from Lego". It most often appears alongside 15th century Sicilian manuscript, Agrimardio, Aigeis.

Reference entry
Lego
Mention count
1
Issue count
1
First seen
September 19, 2023
Last seen
September 19, 2023
September 19, 2023 · Original source
Almost everything that happens to Alexander the Great in The Alexander Romance has also happened to Batman. Alexander invented a submersible to explore the ocean depths; Batman has done the same. Alexander discovered the Fountain of Youth, and so did Batman. Alexander sealed evil nations behind a magic door, and so did Batman. Alexander fought dinosaurs; Batman did too.
Left: Alexander the Great in his makeshift submersible. Right: the Batsub, only $39.99 from Lego! Left: Alexander the Great fights an odontotyrannos. Right: Batman fights a tyrannosaurus. Left: Nectonebo, father of Alexander, a pharaoh who is also a wizard. Right: Amenhotep from the Marvel universe, another pharaoh who is also a wizard. The Alexander Romance is bad in exactly the way comics are bad, and for the same reason. The absolutely bonkers plotlines, the hopelessly bungled continuities, the confusion about its own theology and metaphysics, even the tug-of-war adaptations by cultures trying to claim the hero as their own . . .
Legos

Legos is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "connect Legos, Tinkertoys, Lincoln Logs, etc". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Reference entry
Legos
Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
41: The unfortunately-acronymed Free Universal Construction Kit is “a collection of open source 3D-printable adapters that [enables] interoperability between ten popular children's construction toys”, ie connect Legos, Tinkertoys, Lincoln Logs, etc.
lemoncello

lemoncello is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 09, 2022 and December 09, 2022. The archive places it in contexts such as "a third of the gifts were a bottle of lemoncello". It most often appears alongside 417th Marquess of Cornwallshireshire, ACX, ACX.

Reference entry
lemoncello
Mention count
1
Issue count
1
First seen
December 09, 2022
Last seen
December 09, 2022
December 09, 2022 · Original source
[Most importantly], public displays of family values - If you are smart, wealthy and conscientious enough, you can play the field, settle down late, cheat on your wife, drink a bit too much, and still catch yourself in time to avoid long-term damage. Poor, low-G, high-time-preference people cannot do this. A caring aristocrat will put on a show of moral fibre for the benefit of his charges. Mark Roulo writes: I'll toss this out: Aristocrats grow up expecting that (a) they will be in charge and (b) that they will pass this on to their kids. Part (b) provides a longer perspective than a pure meritocracy where you hope (but, realistically, don't expect ...) your kids to have similar status and power. As folks think shorter term there is less incentive for maintaining the structures rather than benefiting from them and not worrying about whether they will be around in 50 years. Ruet Caelum writes: Another thought I had about the meritocracy debate point is how Brooks' thesis may intersect with the elite overproduction hypothesis. The old aristocracy created arbitrary constraints on the number of elites our country produced. Meritocracy flung the doors open. This is good insofar as it means that more competent people may replace the "arrogant boors who spent most of their energy conspicuously consuming and yachting," but perhaps the resulting culture of intra-elite competition and resentment ends up undermining elite institutions in ways that negate those benefits. I am less sure about this one. “Elite overproduction” means there are more aspiring elites than elite positions. But what is an “aspiring elite”? In a hereditary aristocracy, it’s “children of the last set of elites”; depending on reproduction rate, that can either be many people (bad) or few people (good). In a meritocracy, it’s less clear. Smart people? Graduates of top colleges? But both of these are meaningless - how smart? How top? You would expect that people would eventually become well calibrated, and think “I’m in the top 5% but not top 1% for intelligence/college selectivity, so I can expect a job of X level of eliteness, but not Y level” and in expectation be right. I’m not sure why that hasn’t happened. My guess is that it would equilibrate if it was stable for a while, but many people’s opportunities have been going down compared to their parents’ because of a combination of decreased economic growth, political dysfunction, affirmative action, and rising equality of opportunity. Kade U writes: Re: the question of *why* the old aristocrats might have been good, I can think of couple reasons. Historically, the successful long-lived republics have all basically been oligarchies controlled by ancient, wealthy families that more or less controlled all the levers of power. You're rich and powerful in the Republic because of what your family represents, and similarly you need to live up to the family name. Also, you're a legitimately rich guy who owns a lot of stuff, not just a particularly well-compensated employee, so you generally want rules that help you build stuff and not rules that stop you from building stuff. Meanwhile, you might also be tempted to set up a rent extraction operation via regulatory capture but the other families would rather you not do that because they are all also your business competitors in addition to being your political rivals. Cutthroat meritocratic bureaucracy is more of a mainstay of imperial administrations. The levers of power are held by the emperor's well-compensated, well-educated employees. Those employees have a lot of power in that they make a lot of important decisions, but they are really just custodians of someone else's authority, they have no stake in anything except looking good *within* the system. This works really well if your goal is basically to just execute the emperor's will, since all the employee-administrators will compete with each other to execute it best. But they don't have competing self-interests that make them interested in a pro-business, pro-investment climate. And without a single emperor to hand down the goal of the state, the administrators basically just pick up their cues from whatever they think will increase their social standing within the bureaucracy itself. The nascent tech takeover was basically just an attempt to combine these two ideas by having wealthy, business-interested meritocrats, but it turns out that they do a better job combining the flaws of both systems than they do combining their positives. I would love to see a scholarly, well-thought out comparison between the Imperial Chinese meritocratic system and our own (or else a discussion of why this is a false analogy and wouldn’t illuminate anything). 4. Other Interesting Comments GalenLK on the WASP aristocracy: I don't really buy the premise of the book, but I did wander in to this social circle once by accident in my youth. A friend of mine had by weird historical contingency ended up on one of their soccer youth teams, and got invited along to the parties every year by fiat. I was her plus one. My overwhelming impression was of basically nice (but money-obsessed) noodleheads. During the secret santa (it was Christmas), gift values were all over the map because they didn't have a sense of the difference between $20 and $200, and something like a third of the gifts were a bottle of lemoncello for some reason? Only one or two were employed in a traditional sense, and those were sinecures- part-time work that paid $400,000 a year, to 'tide them over' I think was the phrase; they were embarrassed about it. Another one cornered me pretty early on and started asking a bunch of unusual questions about my personal life, not just where I went to college or what my major was, but odd little details. I was rescued by my date who walked up and said (to both of us), "she's trying to figure out whether you're old money or new money." I just said, "Oh! I am not money." And then we had a little laugh about it and went back to a normal and mutually respectful conversation. They were perfectly nice, really, but it was eye-opening how much it was clearly a social network first, where money just happened to flow very freely and was a primary topic of conversation; it was absolutely a 'class' barrier that I'd crossed, in the old-fashioned sense. I wasn't there nearly long enough to get a bead on the deeper mythologies of the set, but they definitely had a parallel understanding of money that made 'earning' it worse, not better. They were also pretty tryhard about being 'eccentric' and quirky, I guess because it was taboo to talk about accomplishments so they needed something else to talk about over dinner, and the ones winning the game were the ones who made the money seem like it just sort of rained down on them from the clouds. In retrospect, the most interesting thing about it is that all of their wealth depended on internal and inward-facing connections to this group, or I guess being part of inherited/family wealth from it, and nothing depended on any reputation or actions outside of it; they lived on investment income and such, but hired other people to make the investments. So it seems like a sort of socioeconomic 'dark matter' where I have no idea how many people live like this or how much wealth overall they possess. It was just a few dozen at the party, anyway. I'm not sure it even *matters*; I think in economic terms, their function was mostly to be the name at the top of large currency reservoirs being exploited by the financial industry. Whether they're shrinking as a group or holding on in to the 21st century, I have no idea, and I can't imagine there being any broader social consequences either way. Steve Sailer thinks I’m mostly wrong about architecture (and maybe by implication other things?) Architecture: I did a popular long Twitter thread on the change in architecture for city halls before and after 1945, comparing apples to apples: e.g., San Diego's various city halls. Styles were already changing in the 1930s. E.g., San Diego's 19th Century city hall was ornate, but its 1938 city hall was relatively streamlined, but still elegant and nicely detailed. It's 1964 city hall looks like worker housing in Sao Paulo, judging from the lone picture of it I could find online (unlike the many pictures of the two previous city halls. One thing to note: coal-powered cities were so sooty that old buildings had gone dark and ugly and it seemed easier to just tear them down and put up something made of glass and steel. But in 1961, De Gaulle's culture minister Andre Malraux started having Paris's grand old buildings washed, with spectacular results. And also: A late friend of mine taught history at Yale when Yale junked it's Jewish quota for the class entering in the fall of 1965 (a decade behind Harvard). He said even being the grandson of Senator wouldn't have gotten George W. Bush in in 1965 rather than 1964. The intellectual atmosphere of the campus changed immediately in 1965, became much more electric, he recalled. Guy Downs writes: I think an alternative explanation for how we've ended up where we're currently at is that people started inheriting money. This, I think, is the dark matter of the US economy- we know it's everywhere, but nobody can point to it. And I'm not talking about eight figure windfalls coming down from dead shipping scions; I'm talking about the kind of money you'd expect to see run through a family if, since WW II, each generation kept putting away low-mid six figures. You get to the end of the 20th century, and with compounding interest you've suddenly got a lot of people tripping into low seven figure bonanzas when their parents die. So- imagine you're a reasonably self-aware, college educated Democrat, both you and your spouse have solid-but-not-great jobs, and you're making $180k-$210k a year gross. That's not bad, but that does NOT cover: 1) The mortgage on a $450k house. 2) Payments/insurance on two Infinity crossovers. 3) Club sports fees for the two kids. 4) Annual vacations that require air travel. 5) College expenses when the kids get out of high school... And so on. Yet there are millions of Americans who are living that life on these kinds of incomes. So where's the money coming from? And, to the point of this book review, how would coming into that money affect your worldview? Again, assuming the beneficiary is reasonably self-aware, we might expect them to carry some vague sense of guilt and shame at having their lifestyles-- in middle age, no less-- subsidized by monies that they did not year. Which, in turn, could lead to...... 1) a lot of mumbling about 'privilege' (while doing nothing tangible to mitigate its cultural/economic influence),. 2) the pursuit of class signifiers which aren't 'too' grotesque, but which still relay the appropriate message. 3) a desire to use education and 'intellect', as opposed to wealth, as a primary status signifier (since we have both, but only the former was earned) 4) an insistence of minimizing the importance of personal agency in life outcomes (since you 'can't be blamed' for living a life that you haven't really earned) And so on. We talk a lot about the basically uninterrupted spell of economic progress that we've seen since the post-war years, but not (it seems to me) much about how that generational accrual of wealth has affected social standings. My feeling is that its probably driven more of our social outcomes than the people who think the most about these kinds of issues would like to admit. I can’t see more than the faint outline of how Guy is connecting this to Bobos, but I agree that it’s weird. For upper middle class people, inheriting their parents’ money could be the biggest financial event of their lives, maybe bringing them from paycheck-to-paycheck to having six-to-seven figures in the bank, and I never hear anyone talk about it. Probably this is some combination of: Nobody wants to sound like the kind of heartless jerk who is thinking about the upside of their parents’ deaths.
Lencapavir

Lencapavir is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 04, 2025 and September 04, 2025. The archive places it in contexts such as "Lencapavir is dubbed a “miracle drug” for AIDS". It most often appears alongside 80,000 Hours, abundance liberalism, Afghanistan.

Reference entry
Lencapavir
Mention count
1
Issue count
1
First seen
September 04, 2025
Last seen
September 04, 2025
September 04, 2025 · Original source
Meanwhile, tech companies with ten times as much money pretend that they’re cool and playful when their HQ has some rounded edges and a set of colored cubes in front. Do better! 22: Effective altruists have been funding teams working on lab-grown meat for almost a decade now. Around 2020, they hired some experts to double-check that this was possible in principle, and the experts wrote scathing analyses saying it was cost-ineffective by so many orders of magnitude that it was basically a pipe dream. Reactions were mixed, but a lot of us beat ourselves up and vowed to be less gullible next time. But now a new report comes out arguing that the previous reports were wrong, that lab-grown meat production is going much better than the earlier reports thought possible, and it’s more or less cost-effective already for the simplest products! Again, mixed reactions, and although some of the numbers are indisputable the analysis itself this is by a VC firm with lab-based meat investments. Here are some related Metaculus questions. 23: Ozy, citing Stutzman et al: “Afghanistan after the American withdrawal has the lowest life satisfaction rate ever recorded. Two-thirds of respondents rate their life satisfaction below 2, which is generally considered to be the point at which a life is no longer worth living. Life satisfaction dropped significantly after the withdrawal of American troops. Women, people in rural areas, and the poor were particularly negatively affected.” 24: Lencapavir is dubbed a “miracle drug” for AIDS; a single dose protects against infection for six months. Unclear how this interacts with PEPFAR cuts; if PEPFAR still existed it would be a big boost to its efficacy; now maybe this might be part of a strategy to tread water? 25: Did you know: when people first started making artificial ice in the 1850s, there was a backlash from people who thought it was gross and dystopian and that people should insist on natural ice for their iceboxes. From Pessimists’ Archive, which goes on to draw an analogy to lab-grown meat, etc (h/t Isaac King on X). 26: From Peter Hague (on X) and commenter Phaethon: why did so many Anglosphere countries see immigration spikes in 2021? Each of these has their own local story. In Britain, it’s the paradoxical effects of Brexit. In the US, it’s Joe Biden being soft on immigration. And so on - but should we be looking for some deeper cause that explains the overall phenomenon? A commenter suggests “a way to soak up all the inflation from the COVID money printing”, but I can’t tell if that even makes sense. Still, should something something COVID be a leading hypothesis? 27: Jesse Singal vs. Mark Stern on the Skrmetti Supreme Court case that failed to overturn Tennessee’s ban on gender medicine. US law bans sex discrimination, so pro-transgender advocates argued that, since doctors often prescribe eg estrogen to biological women, it was sex discrimination to ban prescribing it to biological men. Tennessee’s anti-transgender argument was that they weren’t discriminating by sex, they were discriminating by diagnosis (estrogen for eg hot flashes, vs. estrogen for gender transition). There is some subtlety here (if a biological man grows breasts because of some hormone imbalance, doctors might give him testosterone to counteract it, and this seems sort of like giving biological women testosterone to make them look less like women), but these are still sort of different diagnoses (gynecomastia vs. gender dysphoria) and Tennessee said you can still think of it as diagnostic discrimination rather than sex discrimination. This makes sense, except that the standards around sex discrimination are very strict and sort of box the court in here. And in a fit of wokeness, the 2020 court (including some of the conservative justices hearing this case) applied these standards very strictly and ruled that discriminating against gays was a form of sex discrimination (since if women can date men, it’s sex discrimination if men can’t also date men), and this is obviously the same argument. Now that wokeness is less popular, the court wants to rule against transgender, but it can’t help tripping over its previous ruling and giving some kind of unprincipled confusing non-opinion. 28: Contra compelling anecdotes, only ~5% of people raised very religious end up atheist later in life (X). Most people are about as religious as their parents; most exceptions are only slightly less religious, and most families that secularize do it over several generations. Note: percentages are of total, not of each row! 29: Related: social science team proposes a three-stage model of secularization: decreased public ritual participation → decreased personal importance → decreased identification, presents apparently confirmatory data. If true, would be somewhat inconsistent with intellectual models (eg people learn about evolution and start doubting the Bible) and more consistent with institutional models (eg the government provides welfare so people no longer need to be part of a tight-knit church). 30: Navigating LLMs’ spiky intelligence profile is a constant source of delight; in any given area, it seems like almost a random draw whether they will be completely transformative or totally useless. Now Ethan Strauss reports that they are, for some reason, extraordinarily effective at teaching people golf. “I am predicting the Golf Revolution, or perhaps decline, if your perspective is that optimization tends to ruin hobbies. A sport for obsessives has been gifted the ideal tool for refinement.” 31: Claim (via nxthompson on X): “In a huge survey of young kids about phones and technology, they all say they want to be out playing in the real world. But parents don't let them out unsupervised. So they're stuck on their phones.” Interesting, but I’m nervous about social desirability bias - how many adults would say on a survey that they would rather be on their phones than playing with friends? But adults do have this choice and mostly go with the phones. 32: Steven Adler on AI psychosis. He tries to analyze ER admissions data for psychosis and finds no change. I don’t think anyone reasonable expected this to be a large enough effect to show up in ER admissions data, but there are lots of unreasonable people so I appreciate his effort. He thinks AI companies might have better data on this, and encourages them to release it. 33: Cuartetera was the greatest polo horse ever. Polo players responded in a very practical way: they cloned her, dozens of times (and it worked; the clones are also excellent). Now there is a lawsuit as different polo teams fight to get their hands on Cuartetera clones. What is the equilibrium? If the outsiders get their hands on the genetic material, do we see a world where every polo horse is a Cuartetera clone? How much is lost if nobody ever tries to breed a polo horse better than Cuartetera (since the economics might not check out if the odds of success for any given foal is too low)? H/T Gwern and Siberian Fox (on X). 34: Claim: as of 2013, India’s Agarwal caste, who make up less than 1% of the population, got 40% of the e-commerce funding. 35: Owlposting: What Happened To Pathology AI Companies? Pathology is a medical specialty. A typical task involves looking at a microscope slide full of cells and trying to determine if any of them are cancerous. This seems like a good match for AI - and for years, studies have been showing that in fact AI can equal human experts. So why isn’t it being used more? The author’s three answers: first, slide scanning is expensive and clunky, and you can’t apply AI to a slide until you digitize it. Second, it’s hard to figure out a business plan where this saves someone money and doesn’t step on the toes of big companies that can outcompete anyone they don’t like. Third, pathologists use the context of a patient’s entire clinical history when they interpret a slide, and AIs that can’t do that (either because of technical limitations or legal/privacy limitations) are at a disadvantage even if their skills specifically relating to slide-reading are better. 36: Noahpinion: Will Data Centers Crash The Economy? Suppose that AI is a bubble, either permanently (because the technology isn’t really transformative) or temporarily (because it can’t transform things quickly enough to keep up with all the dumb money pouring into it). Will the sudden write-off of data centers lead to a broader economic collapse? In 2001, the dot-com bubble harmed the tech sector, but didn’t take the rest of the economy down with it; in 2008, the subprime mortgage bubble did take the rest of the economy down with it, because it damaged banks that the whole economy relied on. The optimistic case for AI is that data center spending is mostly coming from big companies like Google and Meta that can absorb a lot of loss. The pessimistic case is that some of the money is coming from private credit, a new-ish form of finance which hasn’t really been stress-tested and whose failure modes are still poorly understood. Noah’s final verdict: the stage isn’t obviously set for a crisis yet, but there’s the potential to get there and we should consider acting (how?) early. 37: The latest Twitter talking point is that universal hepatitis B vaccination at birth is “woke”: Hep B is (aside from mother-to-child transmission) often sexually transmitted, slutty women’s children are more likely to have Hep B, so perhaps giving the vaccine to everyone (instead of testing and only giving to the children of women who test positive) is an attempt to spare slutty women the embarrassment of getting a positive test. Ruxandra Teslo provides the counterargument - Hep B tests take a while, the medical system is fragmented, and any attempt to test people and then give the vaccine inevitably leads to many positive tests falling through the cracks. Vaccinating at birth is easy and hard to screw up, the vaccine has no known side effects, and empirically child Hepatitis B rates go down (by as much as 2/3!) when countries switch from test-and-vaccinate to universal vaccination. This benefits everyone - even people who never have unprotected sex and always follow up on their medical tests - because toddlers in daycare exchange saliva copiously, and if your toddler exchanges saliva with a Hep B positive toddler they could get the disease. A funny Twitter interaction was seeing Republicans in Congress hop on the anti-slut anti-vaccination bandwagon - except for Senator Bill Cassidy (R-Louisiana), who happens to be a liver doctor, and who is still fighting the good fight. I am always nervous when a good person who I like starts engaging on Twitter, since it elevates the discourse there but also gradually turns their brain into mush - but Ruxandra has made the leap and is doing a great job not just on bio related topics but also (for example) countering Curtis Yarvin on the history of her native Romania. 38: The response to GPT-5 was confusing; most specific people who reviewed it said they were impressed (Ethan Mollick, Tyler Cowen, Nabeel Qureshi, Taelin), it performed as expected on formal benchmarks, but the overall vibes declared it a big failure. Peter Wildeford speculated that maybe there was some kind of sinister pay-to-play early access bias involved. Zvi went the other way, calling it a “reverse DeepSeek moment” (insofar as DeepSeek was a pretty average model that got glowing praise.) In the end, I agree with Peter that this was mostly a branding issue. o3 was a genuinely revolutionary model; if OpenAI had called it “GPT-5”, it would have met expectations. Instead, they called it “o3”, and called a minor incremental update a few months later “GPT-5”. Then people got mad that the exciting-sounding “GPT-5” was merely an incremental update. A secondary issue was that the router wasn’t very good, and so many queries got routed to a small version without thinking mode that was if anything a downgrade from o3. I think this tweet by Shakeel perfectly encapsulates the essence of GPT discourse in two sentences: …but maybe it’s worth asking why GPT-5 isn’t bigger than o3. Was 4.5 a failed attempt at scaling? Did it fail in a way that sort of back-handedly justifies the “lost steam” take? Does the answer depend on distinctions between pre-training scaling, post-training scaling, etc? How? 39: This month in etymology: did you know that “oy vey” is a “fully Germanic phrase” which is cognate with English “oh woe!” (h/t Wylfcen on X) 40: mRNA shows promise to be a game-changing treatment for cancer, but RFK is trying to halt research. But so far he can only starve it of money, not ban it, and the funding gap is only $500 million. Will there be enough philanthropic billionaires and private foundations to step up? Zvi points out that although there is usually a game of chicken where foundations are hesitant to touch something the government cancelled lest the government decide it can cancel everything and hope philanthropists pick up the bill, in this case there are no game theory considerations - RFK is halting it because he genuinely wants it halted, and they are thwarting him rather than playing into his hands. The only problem is that $500M is a lot of money for the private sector; a few foundations could technically afford it, but not many could afford it comfortably and still have money left over for the next few crises of this magnitude. I hope someone is trying to organize a coalition. 41: AI fantasy flash fiction Turing test. Eight stories about demons, four by famous fantasy authors, four by ChatGPT. After 3000 votes, AI wins: humans can't tell the difference and slightly prefer the AI stories. My own score was only 75%. But I will say that I thought Mark Lawrence's was obviously the best, I was ~100% sure it was human, and it convinced me that regardless of the official results it's still possible to write flash fiction that an AI obviously can't do. 42: “SignPro” offers customized “In This House We Believe” signs, try not to use this for evil. 43: China think tank assessment of how in control Xi is: still very in control, maybe not infinitely in control. 44: Related - did you know (h/t xlr8harder) that if you ask AI to write a science fiction story, it will very often name the protagonist “Elara Voss” (or some very close variant like Elena Voss), and this remains true across various models and versions? Related: Chelsea Voss of OpenAI is having a baby and has the opportunity to do the funniest thing. 45: “Hector (cloud) is a cumulonimbus thundercloud cluster that forms regularly nearly every afternoon on the Tiwi Islands in the Northern Territory of Australia…[he is sometimes called] Hector the Convector”. 46: British allergy sufferers who want to know the ingredients of things demand that British cosmetics stop listing their ingredients in Latin. “For example, sweet almond oil is Prunus Amygdalus Dulcis, peanut oil is Arachis Hypogaea, and wheat germ extract is Triticum Vulgare.” 47: Text-based RPG about being an NYT journalist at the Manifest prediction market conference. I make a brief appearance. 48: Study uses supposedly-random variation in doctor assignments to test whether the marginal mental health commitment is good or bad for patients, finds that it is quite bad. Freddie de Boer is violently skeptical (maybe literally so?) and makes some good points about how a single quasi-experimental study is never absolute proof. But I don’t think he quite justifies his opinion that the paper was irresponsible and should never have been published; it’s just a normal quasi-experimental study that we should nod and say “huh” at but not overweight as the culmination of all possible research that overcomes all possible priors. My prior is that the marginal commitment is pretty useless (many commitments are just “well, since this person arrived at our ED for some reason, it would look bad from a medico-legal perspective to just let them go, so let’s keep them a few days to evaluate” - and yeah, you should be upset about this) but I’m still surprised by how many outright negative (as opposed to zero) effects the researchers found. The strongest argument for negative effects is that it will make some people miss work and maybe lose their job. But this study found that commitment ~doubles the risk of near-term suicide (admittedly only from 1% to 2%), which would have been outside my confidence intervals for how bad it could be. I suspect confounding, but only on general principle, and I wouldn’t be too surprised either way. 49: This tweet is probably bait, but I found it a thought-provoking question: I think there’s a boring answer, where the law is more complex than just a single number and whatever kind of weird trafficking Epstein was doing is worse than whatever normal relationships these European laws are permitting. But assuming that there’s a substantive difference even after taking that into account, I think my answer is something like - we’ve got to divide kids from adults at some age, there’s a range of reasonable possible ages, we shouldn’t be too mad at other societies that choose different dividing lines within that range - but having decided upon the age, we’ve got to stick with it and take it seriously (in the sense of penalizing/shaming people who break it). This is more culturally relativist than I expected to find myself being, so good job to Richard for highlighting the apparent paradox. 50: Dilan Esper describes his experience as one of Hulk Hogan’s attorneys in the Gawker lawsuit (X). Parts I found interesting: none of the lawyers knew Thiel was funding the lawsuit; Gawker probably could have won if they had been slightly competent but kept "shooting themselves in the foot"; and Gawker probably could have won if they had just pixelated the private parts in the video. 51: Amazing concept and poems (link on X): I tried to see if AI could do this, and it did something that technically met the requirements but had zero artistic merit - using a lot of words like “nowhere” and “outside” in one, then separating them out to “no where” and “out side” in the other. I didn’t invest much energy in creating a clever prompt telling it not to do that, so feel free to report if you get better success. 52: New study claims consultants are actually good, at least for profits: "We find positive effects on labor productivity of 3.6% over five years, driven by modest employment reductions alongside stable or growing revenue" 53: A Polish team tries to test Peter Turchin’s equations for predicting political unrest on recent Polish history, has to make some changes but claims mostly positive results. 54: New big multi-author Substack, The Argument, trying to be a sort of center-left version of the model pioneered by The Free Press and other high-production-value ideological Substack properties. Excited to see Kelsey Piper is involved, and she starts off strong with a post on the latest round of First World basic income studies, which find few positive effects. This is surprising, because recipients didn’t waste the money on alcohol or gambling or anything - they paid down debt and got useful goods. Still, it didn’t even affect things that should have been obvious, like stress level. It’s not even clear that amounts of money large enough to help with rent made homeless people more likely to get houses! Matt Bruenig criticizes the article, accusing Kelsey’s studies of being downstream of Perry Preschool style dreams that exactly the right welfare program will have massively compounding effects that cut poverty out at the root and turn everyone into elite human capital; he thinks giving people money won’t do this, but it will increase equality and give the poor better lives. I assume he’s not a strong hereditarian, but his argument makes even more sense from that perspective, and I’ve certainly criticized dumb outcome measures like infant brain waves which we have only tenuous reasons to think are related to anything we care about. But Kelsey reasonably responds that the outcome measures she’s talking about include stress level and life satisfaction. To defuse this critique, Bruenig either has to argue that our construct “life satisfaction” doesn’t really measure whether someone’s life is satisfactory, or else claim that giving poor people satisfactory lives isn’t really what we’re going for - which I think would require more explanation on his part. There’s some further (impressively acrimonious) debate on X, but I don’t see anything that addresses my core concern. GiveDirectly, a charity involved in basic income experiments, has a presponse here; they say that some studies are positive, and that the ones that aren’t might have tried too little cash to matter, or been confounded by COVID making everything worse. They also point out that basic income is harder to study than traditional programs like giving people housing, because if you’re giving housing you can measure housing-related outcomes directly and have a pretty good chance of getting enough statistical power to find them, but since everyone spends cash on different things, the positive effects might be scattered across many different outcomes (and therefore too small to reach significance on each). Everyone involved in this debate wants to emphasize that the poor results are for First World studies only, and that studies continue to show large benefits to giving cash in the developing world. 55: Related: I was less impressed by The Argument’s first foray into housing policy, which follows an all-too-familiar pattern: Some people say they don’t like noise and disorder and try to make rules against it in their apartments.
leuprolide

leuprolide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "a medication (leuprolide) that suppresses oestrogen and progesterone". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
leuprolide
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
In an elegant series of experiments, Peter Schmidt and David Rubinow gave participants a medication (leuprolide) that suppresses oestrogen and progesterone. This eliminated PMDD symptoms. Whats more, when they reintroduced either oestrogen or progesterone, symptoms returned.
Life Extension

Life Extension is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "Others like Life Extension, Jarrow, and NOW have most things pass with only some failing". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Life Extension
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
NOW has their own in-house lab, and they have been trying to clean up the standards of the industry for a while. We have had a couple things of theirs fail, but only for content lower than label claim, not fake or impure or anything like that. So while I wouldn't say trust everything from them 100%, NOW is one of the better ones in this industry seemingly trying to make things better. I also have more trust for Thorne than most […] every single brand we have tested so far has had at least one thing fail, save for Thorne. Some of the brands have almost everything fail. Others like Life Extension, Jarrow, and NOW have most things pass with only some failing. It's a crap shoot.
LIH383

LIH383 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 15, 2024 and May 15, 2024. The archive places it in contexts such as "His most promising lead is LIH383, a chemical which seems to increase the brain’s natural opiate tone". It most often appears alongside @the_megabase, A Pan-Species Welfare State, ACX Grantees.

Reference entry
LIH383
Mention count
1
Issue count
1
First seen
May 15, 2024
Last seen
May 15, 2024
May 15, 2024 · Original source
For a philosopher, Pearce is very practical. Sure, he has dozens of essays on why it’s morally correct to end suffering. But he also wants to start the project himself. You can read his analysis of dozens of drugs and how they might contribute to some kind of hypothetical future “make everyone happy all the time” cocktail. Early on, he rejects the obvious choices - heroin, cocaine, SSRIs - for the obvious reasons. By the end, he’s investigating weird drugs that even I - who have kind of made a career knowing about weird drugs - have never heard of. Apimostinel originally looked promising, but failed Phase 3 trials. Nomifensine seemed promising but was later found to cause a serious blood disorder. His most promising lead is LIH383, a chemical which seems to increase the brain’s natural opiate tone, potentially producing the effect of a small dose of opiate without any negative effects or addiction potential. But this is way past his ability to test, and so far he hasn’t been able to interest any pharma companies.
(I tried a distant LIH383 relative once, for Science, but didn’t notice any effect)
Lincoln Logs

Lincoln Logs is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "connect Legos, Tinkertoys, Lincoln Logs, etc". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Reference entry
Lincoln Logs
Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
41: The unfortunately-acronymed Free Universal Construction Kit is “a collection of open source 3D-printable adapters that [enables] interoperability between ten popular children's construction toys”, ie connect Legos, Tinkertoys, Lincoln Logs, etc.
lisdexamfetamine

lisdexamfetamine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 16, 2022 and November 16, 2022. The archive places it in contexts such as "patient who took selegiline and lisdexamfetamine". It most often appears alongside @AutismCapital, Adderall, ADHD.

Reference entry
lisdexamfetamine
Mention count
1
Issue count
1
First seen
November 16, 2022
Last seen
November 16, 2022
November 16, 2022 · Original source
Also, Israel 2015, Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination follows a patient who took selegiline and lisdexamfetamine at the same time, notes with surprise that they didn’t die, and concludes that:
LLaMa

LLaMa is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa"; "twelve LLMs - including ... LLaMa". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
LLaMa
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
Lockheed Martin

Lockheed Martin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 24, 2022 and June 24, 2022. The archive places it in contexts such as "PNAC (created by Lockheed Martin) lobbyists"; "war hawks (neocons like Cheney i.e. products of Lockheed Martin)"; "Lockheed Martin received $36 billion in government contracts in 2008". It most often appears alongside 501(c)(3), 80,000 Hours, 9/11.

Reference entry
Lockheed Martin
Mention count
1
Issue count
1
First seen
June 24, 2022
Last seen
June 24, 2022
June 24, 2022 · Original source
funding movements, as in the case of neoconservatives who pushed for Saddam’s overthrow, the movement was spearheaded by PNAC (created by Lockheed Martin) lobbyists who would go on to become Bush administration officials like Rumsfeld, Wolfowitz, Cheney and Weber;
Counterinsurgency (COIN) In the case of Afghanistan, the Bush administration was so eager to go to war it avoided any other options. No evidence has ever emerged that Taliban (the political faction that ruled Afghanistan at the time) itself knew about the 9/11 attacks, much less planned it; the Afghan ambassador to Pakistan condemned the attacks on 9/12. “We don’t negotiate with terrorists” became the standard American line — before the war began, Taliban was willing to discuss bin Laden’s fate but the White House Chief of Staff refused; after the war began, Taliban was willing to hand over bin Laden to a third country for trial but White House refused just the same. In the case of Iraq, Bush was so eager to, in his own words, “Fuck Saddam, We’re taking him out” as early as February 2002 (and floated the idea of invading Iraq to Tony Blair), that on 9/17 Bush told his cabinet “I believe Iraq was involved, but I’m not gong to strike them now. I don’t have the evidence at this point.” The administration couldn’t find any evidence directly tying Saddam to 9/11, so they settled on the now-discredited lies of WMDs and “ties” between al-Qaeda and Iraq. “We don’t negotiate with terrorist”’ extended to the non-terrorist Saddam — before the war, Saddam was cooperating with the International Atomic Energy Agency; after the war began, Saddam was willing to accede to practically all Amercan demands but White House refused communication just the same. Just like in Afghanistan, the Bush administration had no interest in exploring any other option short of war. Two feuding factions within the Bush administration had little contact with each other: the war hawks (neocons like Cheney i.e. products of Lockheed Martin), supported by the Pentagon, did not want to do nation-building; those partial to nation-building (the State Department) did not want war. Bush agreed with the former at the start of the war, but once Saddam was removed, sided with the latter. The postwar plan for Afghanistan was officially determined by the Bonn Agreement of 2001, but neither Bush nor Cheney consider it to be worthy of much thought in their memoirs despite years of hindsight; the postwar plan for Iraq lay entirely in the hands of Paul Bremer as subsequent Deputy Committee meetings on Iraq stopped being conducted — there wasn’t a single meeting to discuss disbanding the Iraqi army that left 400,000 jobless former soldiers prime for insurgency. The Iraq war dealt with no real crisis but cost the US trillions of dollars and thousands of lives, plunged Iraq into two decades of intermittent civil war — a candidate for the worst American foreign policy failure in history, but a success for the careers of Bush (who won reelection and congressional seats) and his advisors who led the US into Baghdad (who went on to work for think tanks, the World Bank, and the Trump Administration). Once again, there is no grand strategy as each party was only self-interested in short-term gains. The Earlier Obama Years As a candidate, Obama campaigned in support of the Afghanistan war, and indeed his first foreign policy decision as president was to send thousands of additional troops to Afghanistan, largely due to overwhelming political pressure from top generals like Petraeus and McChrystal who boxed Obama into sending more troops by limiting the options presented to Obama, blatantly lobbying in press interviews, and threatening dire consequences like resigning from commanding troops in Afghanistan. We know Obama was hesitant as he announced at the same time that American troops would begin withdrawal in July 2011 (by 2015 he announced that American troop presence would stay in Afghanistan indefinitely). Obama’s second decision was to bomb al-Qadhafi in the name of Libyan regime change, due to domestic but this time also international political pressure from the heads of France and the UK who would face political embarrassment if Qadhafi’s regime, despite months of bombing and sanctions by the US-led coalition, recaptures the rebel-held Benghazi. NATO forces bombed al-Qadhafi’s convoy. Ten days after the killing of the dictator, the bombing campaign ended, and the subsequent decade of intermittent civil war faded from the American consciousnesss. Obama’s third decision was to cripple Assad’s regime in Syria with sanctions and by arming and training rebels, again due to overwhelming political pressure from hawkish ‘foreign policy community’ who still criticise Obama for having ‘done nothing’ despite spending $1 billion through the CIA and $500 million through the Pentagon, and crushing the Syrian economy. Top officials in the Obama administration admitted that assisting rebels would not change the course of war, nor was there any way to prevent arms from ending up in the hands of ISIS and al-Qaeda. Indeed, the Syrian civil war only got bloodier with American involvement. The Later Obama Years Obama’s first major decision was the war on ISIS with the reentry into Iraq from which all American troops withdrew just a few years ago in 2011, due to overwhelming political pressure and in the face of a potentially humanitarian catastrophe (ISIS was going to massacre the Yazidi religious sectarians in Mount Sinjar). This time, the United States would roll back all territorial gains of the Islamic State by working with the Iraqi government, Shia militias in Iraq, and the Kurdish-led Syrian Democratic Forces. Obama’s second decision was signing the Joint Comprehensive Plan of Acton (JCPOA) with Iran to stop its nuclear weapons programme in exchange for UN and EU sanctions to be lifted, $100 billion in assets seized by the US to be returned to Iran, and the US to stop implementing secondary or third-party sanctions. This time, Obama faced unusually significant pressure from Congress which passed the Iran Nuclear Agreement Review Act by overwhelming majority to be able to revoke JCPOA, but Obama signed JCPOA with Iran nonetheless as enough Democrats would be able to sustain a veto. This was the one and only decision that made sense from the perspective of classical IR theory — American leaders doing things they think are right for the country without a clear political payoff. Indeed, the Iranian nuclear agreement is the exception that proves the rule of public choice, as the deal was only possible near the end of Obama’s second term, and at the end cancelled by Trump upon entering office — a president’s foreign policy accomplishment made without the support of concentrated interests only lasted as long as his administration. 6. Learning From American Foreign Policy Failures IR theorists widely acknowledge that it was a mistake to invade Vietnam and Iraq, and even the war in Afghanistan went on for too long even if it was originally justified, but these scholars have yet to comprehend the shortcoming of the unitary actor model in accounting for the lack of rational cost-benefit analysis. Comparing the pre-invasion GDP of the countries to what the US has sacrificed (even setting aside the number of lives lost), the GDP-to-money-spent ratio has been 1:74 in South Vietnam, 1:43.3 in Iraq, and a staggering 1:396 in Afghanistan. In other words, the United States has spent in Afghanistan the equivalent of that country’s level of production for close to four centuries. Cost-benefit analysis also fails outside the major wars: NATO, despite the collapse of the USSR, is willing to absorb practically any country including states that can drag the US into war without contributing anything to American security; the military expenditure in Japan and South Korea, despite anti-China talks in Washington, are either flat or declining. While an utter failure in humanitarian and economic terms, American foreign policy has a been a resounding “success” from the public choice perspective: Lockheed Martin received $36 billion in government contracts in 2008 alone (more than any company in history)
Lockheed Martin received $36 billion in government contracts in 2008 alone (more than any company in history)
Loom

Loom is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2022 and September 19, 2022. The archive places it in contexts such as "Janus has developed Loom, a tool to write with GPT-3 more efficiently". It most often appears alongside AskReddit, Conjecture, Dittomancy.

Reference entry
Loom
Mention count
1
Issue count
1
First seen
September 19, 2022
Last seen
September 19, 2022
September 19, 2022 · Original source
How does it get this level of self-awareness? In this case, via rigged demo. Janus has developed Loom, a tool to write with GPT-3 more efficiently. It turns stories into branching trees where you can choose which of multiple completions to pick at any given point.
But sometimes GPT-3 genuinely gets it right. The most common way for that to happen is (again) by mistake. A common failure mode is to repeat the same sentence several times. GPT-3 was trained on a corpus of Internet text, and some of the Internet text was discussions of GPT-2. Many of the samples it saw that repeated the same sentence over and over in an endless loop were discussions of GPT-2 doing this. So sometimes it will get stuck in a loop, then end with “This is an example of text produced by a transformer language model”. This sounds like a stupid example from a Philosophy Of Self-Awareness class, but sometimes it really happens. Here’s an example from one of Janus’ attempts to generate Loom documentation:
Based on your interactions with the AI, Loom constructs your labyrinthian multiverse as a "labyrinthogram", exploring genealogically contiguous regions of possible language relating to the same theme as you drive. Here are some small samples of labyrinthograms. This multiverse is about introducing Loom. The first continuation from the first serial labyrinthogram above is: Then for the two next continuities the computer went: and and and and and and This essay discusses how to use GPT-2, a large probability language model.
lornafarnib

lornafarnib is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 01, 2021 and June 01, 2021. The archive places it in contexts such as "a drug called lornafarnib". It most often appears alongside Alzheimers, beta amyloid plaques, FDA.

Reference entry
lornafarnib
Mention count
1
Issue count
1
First seen
June 01, 2021
Last seen
June 01, 2021
June 01, 2021 · Original source
There's been a lot of research on one important form - Hutchinson-Gilford Syndrome - and just last year, the FDA approved the first treatment, a drug called lornafarnib. In the study, a few hundred children averaging around 7 years old took the drug for two years; 3% died during that time. In an ad hoc group of untreated comparison children, about 30% died during the same period. I'm a little confused by the methodology - it seems like the "comparison children" were chosen partly because they died too early to get into the trial, which sounds like a pretty major confounder - but everyone seems to treat this as reasonable so I will assume they adjusted for this in some way. If that's true, then lornafarnib cuts mortality by 90%.
That's great for the 300 or so children worldwide with Hutchinson-Gilford progeria (it's a really rare disease). But none of the discussion about this answered the question I wanted to know: can lornafarnib also prevent normal aging?
Lornafarnib interferes with the production of the defective progerin protein. As best I can tell, it doesn't cause the cell to produce healthy lamin A - it just prevents the defective mutant version from accumulating. For whatever reason, the cells without lamin A do surprisingly okay as long as they don't have the defective mutant version. So this prevents most of the DNA repair problems, and so decreases premature aging.
Lovaza

Lovaza is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 12, 2021 and May 12, 2021. The archive places it in contexts such as "Maybe you’ve read my old post on Lovaza ? Lovaza is prescription fish oil"; "oil is just as good as Lovaza". It most often appears alongside Alexander Pope, CBT-i, Cognitive Behavioral Therapy For Insomnia.

Reference entry
Lovaza
Mention count
1
Issue count
1
First seen
May 12, 2021
Last seen
May 12, 2021
May 12, 2021 · Original source
Maybe you’ve read my old post on Lovaza? Lovaza is prescription fish oil. You can get non-prescription fish oil from any supermarket or supplement store for $10 per Giant Jar. Or, if you prefer, you can go to a doctor and get prescribed Lovaza for $300 a month. Is there a difference between Lovaza and regular fish oil? Other than the 30x markup and prescription-gating, no. Nor is there much difference between regular methylfolate and prescription Deplin. You can get some effective treatment for very cheap as a supplement. Or you can get the same treatment for much more money as a prescription medication.
It’s hard and expensive to get a product into the official medical system. You need to produce studies for the FDA (it doesn’t matter if dozens of studies already show fish oil works, you need to do new studies) and prove you’re complying with various regulations. By the time you’ve done all those things, you’ve spent a lot of money. And also you have a sort of monopoly, in that you’re the only company whose fish oil is FDA approved and able to interface with organizations who will only work within the regular medical system (eg insurance). So you increase the price by 30x. Patients are fine with this, because their insurance foots the bill. Insurance companies are fine with this, because the law demands that they be fine with it. Even if you or I know that normal fish oil is just as good as Lovaza, the official medical system doesn’t know this, and the insurance company is not allowed to make use of this knowledge.
Luckyfish

Luckyfish is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "Luckyfish ... have signed and published FFF's fish welfare commitment". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
Luckyfish
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
Lumina probiotic

Lumina probiotic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 13, 2024 and May 13, 2024. The archive places it in contexts such as "predictions I made in my update on the Lumina probiotic". It most often appears alongside 17 CFR Part 40, 2024 election, Austin.

Reference entry
Lumina probiotic
Mention count
1
Issue count
1
First seen
May 13, 2024
Last seen
May 13, 2024
  • 24 May 13, 2024
May 13, 2024 · Original source
This is a response to the predictions I made in my update on the Lumina probiotic. You can click “see three more answers” for the question on side effects (separate from this question on efficacy). My numbers were 5/35/10/50 for the first question and 30/5/<1 for the second.
Luna

Luna is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 14, 2023 and February 14, 2023. The archive places it in contexts such as "a cryptocurrency dating site called Luna"; "Luna failed for two reasons. First, they never delivered more than an extreme bare-bones prototype". It most often appears alongside Aella, Austin, clown dating site.

Reference entry
Luna
Mention count
1
Issue count
1
First seen
February 14, 2023
Last seen
February 14, 2023
  • 23 February 14, 2023
February 14, 2023 · Original source
Unfortunately, it’s now common knowledge that people will sometimes say yes in person when they haven’t checked you on Reciprocity, which means you’re back to having to decide whether or not to ask your crush on a date. Tragic! Alas, Poor Luna A basic problem with dating sites: attractive women tend to be overwhelmed with messages (many of very low quality) and eventually lose interest in reading them. Meanwhile, men spend an hour crafting the perfect missive and get no response, thirty times in a row. Both sides end up feeling dejected and exploited.
Back in 2018, I wrote about a cryptocurrency dating site called Luna. The idea was: men pay to send messages. Women get paid for reading them. The exact rate scaled based on how crowded the woman’s inbox was and how much she valued her time at, but was expected to be in the low single-digit dollars per message. This incentivizes men to only send messages that have some chance of producing value (eg not spamming every single person in their area with “hey u r hot want 2 fuk?”), and incentivizes women to actually take some time to read their messages (I think there was some plan that they would only get the money if they took some action suggesting the message had actually been read, like spent a while scrolling down on it in their browser window).
Luna failed for two reasons. First, they never delivered more than an extreme bare-bones prototype; it might have been a scam all along (see: “cryptocurrency dating site”). Second, almost no women signed up (see: “cryptocurrency dating site”).
Lyft

Lyft is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 04, 2022 and November 04, 2022. The archive places it in contexts such as "Proposition 22 (make it hard for Uber and Lyft to do gig employment)"; "this proposition is funded entirely by Lyft". It most often appears alongside ABSTAIN, Alex Padilla, American Nurses Association.

Reference entry
Lyft
Mention count
1
Issue count
1
First seen
November 04, 2022
Last seen
November 04, 2022
November 04, 2022 · Original source
Until now, Proposition 22 (make it hard for Uber and Lyft to do gig employment) was the most expensive proposition in California history. But it looks like Proposition 27 is going to beat 22 for this heavily-contested title. It lets out-of-state companies provide online sports betting in California if they bribe some Indian tribe that has gambling rights to say the Indian tribe supports them.
According to this website, which I trust because it’s too hilarious not to be true, this proposition is funded entirely by Lyft. The wildfire prevention is a diversion, and most of the money goes to tax breaks for electric cars. Lyft needs lots of electric cars to meet some new regulation, and would save a lot of money if California subsidized electric car purchases. Actual environmentalists prefer things other than pure electric car subsidies, and this proposition deliberately locks them out of the decision-making process. Newsom and his allies in the teachers’ unions are against because you can only use the rich as a piggy bank some limited number of times before they move out, and this funges against the stuff they want to tax them for.
Probably this will pass, because Californians respond to “tax the rich to fund environmentalist-sounding-thingies” like sharks respond to chum. Probably the California government deserves it, because they keep coming up with dumb laws to hurt Lyft, and turnabout is fair play. Still, corporations using the rich as their personal piggy bank is a worrying development even by California standards. Also, I hate Lyft because their app keeps pretending it’s right on the verge of finding me a driver, then stringing me along for ten minutes before admitting there are no drivers within miles of me. I vote NO.
M-PESA

M-PESA is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 04, 2024 and April 04, 2024. The archive places it in contexts such as "Kenya’s M-PESA cellphone cash really helped their economy". It most often appears alongside Aaron Peskin, ACLU, AGI And The Efficient Market Hypothesis.

Reference entry
M-PESA
Mention count
1
Issue count
1
First seen
April 04, 2024
Last seen
April 04, 2024
April 04, 2024 · Original source
16: New African company tries to do cellphone-based cash using crypto. Kenya’s M-PESA cellphone cash really helped their economy; other African countries tried to replicate it but due to different governments and stakeholders weren’t able to make it work. I don’t know enough about the constraints to predict whether this avoids them, but I wish it well.
M:TG

M:TG is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 27, 2023 and April 27, 2023. The archive places it in contexts such as "Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing)". It most often appears alongside 286, 8088, Adorno.

Reference entry
M:TG
Mention count
1
Issue count
1
First seen
April 27, 2023
Last seen
April 27, 2023
April 27, 2023 · Original source
…where Sam fills in the northwest and southeast squares, then claims a correlation, draws a line, and points to high-status/deep-engagement as a single unified concept. But the southwest square could be “writes a wacky Shakespeare fanfiction, Romeo & Juliet II, in blank verse and period-appropriate language”, and the northeast square could be “publishes a dissertation on some irrelevant aspect of word frequency changes across English plays to prove something about linguistics”. And then having conflated these two things, he goes on to conflate a third thing, Shakespeare vs. Marvel. I’m not up to date on what goes on in academic literature departments, but Freddie de Boer says they’re increasingly offering “Spiderman Studies” classes in attempts to stay culturally relevant; probably Spiderman professors engage with Spiderman on the same deep level that Shakespeare professors engage with Shakespeare. If we made this a cube - high-status vs. low-status forms of engagement along one axis, Shakespeare vs. Spiderman along another axis, and deep vs. shallow engagement along the third - would anything be left of the “nerd” cluster as Sam describes it? I’m not sure. 2. Comments With Strong Opinions On The Definition Of Nerds, Geeks, Etc There were many of these. One common theme was that in the 70s, “nerd” was almost synonymous with “person who is only into unpopular things”, for example sci-fi, comics, and RPGs, all of which were unpopular in the 70s. Then those things became very popular, but the people who were interested in them still get called “nerds”. So now people like Kriss use “nerd” almost synonymously with “person who is only into popular things”. So we have a word which denotes either interest in unpopular things or interest in popular things, depending on who’s using it and when they last updated their lexicon. In the 70s, it was more reasonable to group “interested in math and computers” and “interested in sci-fi and RPGs” together, because both were unpopular and tended to involve the same group of socially maladept young men. Now math is still hard and unpopular; computers are hard in the sense that it’s tough to learn programming languages, but universally used and beloved; sci-fi and RPGs are very popular, and the typical sci-fi fan is closer to a socially-adept albeit “quirky” young woman. If words are hidden inferences, the inference represented by “nerd” - that sci-fi fandom, interest in math, interest in computers, maleness, poor social skills, and nonconformity with mainstream interests all go together - is now thoroughly false, dooming us to conversations like this one. Attempts to repurpose the several different words used to refer to the math/sci-fi/awkward/unpopular cluster to represent different aspects of its successor clusters have mostly failed. Sample comments from this section: Coagulopath writes: To me, being a nerd requires a degree of swimming against the cultural tide. It's weird and unpopular to be into trains, so the fact that you are indicates you have a bit of character (or are socially oblivious, which is also kind of endearing). The problem (and I think Kriss alludes to this) is that nerd stuff went mainstream in the past few decades. Of the 10 highest-grossing movies of the 2010s, 6 are Star Wars or Marvel films. There's no longer any sense that nerds are the underdog. But what does it say about you when you wear a Star Wars shirt? You're pledging allegiance to the biggest, most popular club imaginable. Is that a brave stance? Those people always make me think "if you lived in the SW universe, you'd be on the side of the Empire". In general, I am creeped out by effusive public adoration for things that are near-universally loved. Like The Beatles. Or bacon. Or dogs. Or science (Neil DeGrasse Tyson's whole shtick). Regardless of how I feel about those things on the object level, there's no glory in joining a culture war when you're signing on to the winning side. Tolaughoftenandmuch writes: All this is so different from when I was a kid. I was a nerd because I was intellectually curious, bad at and disinterested in sports, socially awkward, and had a computer hobby (owning hardware C64 ->8088 ->286, writing programs in Basic, being a BBS SysOp). Cultural interests were irrelevant to my nerd status. In terms of exactly when nerd interests started becoming popular, Ghatanathoah writes: I also wouldn't say that nerd stuff only went mainstream in the last decade, it's not like the first 3 Star Wars movies were obscure arthouse pictures. I think the reason Marvel took off is just innovations in storytelling: movie producers finally figured out a way to adapt the gloriously arcane and convoluted lore of superhero comics in a way that could appeal to mainstream audiences in addition to nerds (much how George Lucas figured out how to get mainstream audiences to love the space operas nerds had been enjoying for decades before 1977). And Melvin writes: Comic book movies had always been pretty popular. Superman was the top grossing movie of 1979 despite coming out in 1978. Superman 2 was the second top grossing movie of 1981. Batman was the second top grossing movie of 1989. Batman Returns was the top grossing movie of 1992. Batman Forever was the top grossing movie of 1995. Spider-man was the third top grossing movie of 2002 (behind Lord of the Rings and Harry Potter movies). That's about all I can be bothered looking up right now but you get the idea, superhero movies have been popular since the 1970s. Kaitian writes: I think being a nerd requires being a bit socially clumsy about your interest, and talking or signalling about it in situations where most people don't expect it. So being a nerd about completely mainstream stuff like pop music or football is not possible, that's just fandom. Being a nerd about very well known and relatively well-respected stuff like classical music or birdwatching is rare, because most people who are classy enough to care about the thing in the first place are also classy enough to know when to shut up about it. But comics? Star trek? Power metal? They have fairly low barriers to entry *and* most people don't care about them, so there's plenty of opportunities to bring it up to people who don't want to hear about it. So that's why I think nerdery usually attaches itself to the typical targets. J.R. Leonard has as good a terminology proposal as anyone: I think what's missing is that Kriss uses "nerds" as his foil, but what he's talking about would better be described as fan culture. Deiseach teaches us the etymology of “geek”. The very distant etymology is from German gek, a relative of “cackle” → geck, a fool/madman (who was presumably cackling all the time). But this comes down to us through the early American institution of the geek show. From Wikipedia (cw: disturbing): Geek shows were an act in traveling carnivals and circuses of early America and were often part of a larger sideshow. The billed performer's act consisted of a single geek, who stood in the center ring to chase live chickens. It ended with the performer biting the chickens' heads off and swallowing them. The geek shows were often used as openers for what are commonly known as freak shows. It was a matter of pride among circus and carnival professionals not to have traveled with a troupe that included geeks. Geeks were often alcoholics or drug addicts, and paid with liquor – especially during Prohibition – or with narcotics. More obvious but I went surprisingly long without realizing it: “fan” (as in “sports fan”) is just short for fanatic. 3. Comments About Collecting The veteran collectors in the comments said that my theory (the Internet makes collecting too easy) was only a small part of the decline. The bigger part is that most coin collecting begins with the wonder of finding a rare coin in your change, and most stamp collecting begins with the wonder of finding a rare stamp on your mail, and the rise of credit cards and emails means people aren’t handling coins and stamps as much in their daily lives. Tom Metcalf writes: I'd guess many coin collectors got their start being patient enough to sort through change to see if they had e.g. a wheat cent or silver dime, but first of all, who pays with cash and gets change, and the chances of finding something collectible are orders of magnitude smaller than, say, the '90s. And stamp collectors would have started saving the stamps on mail sent to their house, but how frequently do you get stamped mail anymore? My 79-year old father goes to stamp shows, because one of his hobbies is to buy sheets of old but common unused stamps for less than face value. They are still valid postage, and then he uses them to personalize the stamps he puts on letters he sends to various people. And most of the other people at stamp shows are about his age. He does have some stamps he thinks are interesting that he's held onto, but the dealers at the stamp shows think they're common and uninteresting. So there's a decreasing number of stamps that might be "worth something" and a net loss of collectors in the hobby, and then every time a collector dies and his heirs have no interest in his collection and that many more stamps make their way to dealers who now have one less buyer. Too bad "sending paper letters with vintage but still valid stamps" never caught on with the hipsters. Art writes: The widespread adoption of email created a world where a letter is almost certainly junk mail or a bill. Nobody looks forward to hearing from a good friend from across the country now when picking up the day’s mail. If letters are not interesting why would stamps? The same for coins. Nobody uses cash, and getting a pile of coins with no significant value (inflation) is just an annoyance. These objects have passed into irrelevance. Still, it seems like some little pieces of joy and wonder have passed from our lives. Nathan Savir writes: I collect coins and I think the description of the hobby (and its putative death) isn't quite right. 1. Rare coins are in fact hard to find, even in today's internet world. They are usually sold in auctions, which might happen online, but still not that frequently. It's not unusual for examples some specific rare coin to be sold only once every few years. If the coin is also obscure, it may not be prohibitively expensive, so this kind of situation isn't the sole province of rich people. 2. One area of collecting is to get all the rare items. Another is to get all the minor varieties of a common item. These varieties may not be very rare, but it still takes a lot of effort to be able to distinguish them and to find them. Some collectors will obtain large numbers of relatively common coins and sort through and scrutinize them to try to identify interesting varieties. 3. An important part of collecting is getting good deals. This is surely a lot harder than it used to be because sellers can more easily figure out what things are worth and you won't find something grossly underpriced in a random antique store as often these days. But filtering through buckets (or online listings) of large numbers of coins can still be fun and lead to spotting good deals. So I think there is room in the hobby for nerd-like behavior (per your definition). I would argue the decline of the hobby is more due to competition from other similar hobbies (a generation ago you could collect stamps, coins, baseball cards, or rare books/comics - now you can collect beanie babies, Pokemon cards, NFTs, funko pops, action figures, etc.). I think stamps have suffered more than coins because stamp collecting has more of an aesthetic component (which has faced stronger competition) while coins have a historical element that is less well replicated by collecting newer things. This difference isn't obvious in the google trends graphs you posted but I believe is observable from looking at prices of stamps vs coins. I asked Nathan what coins he collects that are still tough to find, and he gave the example of this Yuan dynasty coin from 1350. I guess if you want to be a collector in 2023 you need to go hard. Arrk Mindmaster writes: I used to collect US coins from every denomination, year, mint, and variety (such as large and small date 1960 pennies). It was kind of like a treasure hunt, knowing you could find something in circulation that was actually more valuable than most people thought it was. I lost interest in the late 1980s sometime, when I found the volume of new coins dwarfed older coins. For example, for Lincoln pennies, they used to make a few million per year, then a few tens of millions. In the 80s, they started making about 5 BILLION each, and it started drowning out all of the old coins, which basically stayed the same value. This comment snapped some things into place for me; I collected coins as a kid in the 90s, and older coin collectors would talk as if you could spot some pretty rare things in your pocket change. But I had much worse luck, and it’s been years since I’ve even found a wheat cent in circulation (even when I was a kid this would happen occasionally). Maybe coin collecting is dying not just because we don’t use change, but because our change is less likely to have interesting coins in it. Another victim of mass money printing! The new state quarters sort of fix this, but other commenters express contempt for this. It feels like the transition between old myths (which one can enjoy) to the Marvel Cinematic Universe (which corporations are begging you to enjoy in a pre-approved way) - now that the Mint wants you to collect their coins, it feels kind of slavish to comply. Other people point out that the collecting of things other than stamps and coins is still going strong. Drethelin: Collecting has not in the slightest died out. People collect more things than ever, like sneakers, funko pops, vintage cars, guns, antique ceramics, anime figurines, magic cards, etc. Some people also brought up NFTs - are there lots of people who truly enjoy collecting NFTs, aren’t just in it for the investment value, and have kept up through the crypto bear market? 4. Comments Insisting That Sports Are Good Aris C writes: It's a little glib to dismiss sports as bad, isn't it? Athletes display extreme skill, sometimes transcendent. I don't think watching people push the limits of human ability is obviously bad. When I said sports were bad, I didn’t mean this as a final value judgment. I meant that, by our usual standards of entertainment, sports are bad. Imagine a sitcom which had several thousand episodes, each with the exact same plot (some people try to get a ball from one side of the court to the other). At some point, surely most people would stop watching! I appreciate the something something human spirit, and I’m happy to know that, somewhere in the world, sports are happening. It’s just the decision to actually watch them that confuses me. 5. Comments About Enjoying Things Vs. Building Identities Around Them Many people complained that some combination of me and/or Sam Kriss were denying that anyone can ever enjoy anything except as an attempt to “gain status”. I would answer first that yes, I think most behavior has some status component (although it may be a small component, mixed with genuine enjoyment). But also, it doesn’t seem mysterious that some people eg like Star Wars, or even love Star Wars. What seems mysterious to me is when this expresses itself as desire to buy thousands of dollars of figurines in the original boxes, or memorize the stats of every class of ship in the Imperial Navy, or something else which doesn’t seem very fun on its own merits. I’m not criticizing others from a place of invulnerability here. When I was ~14, I got really into Star Wars, and aside from reading all the Extended Universe books - some of which were genuinely very good - for about a year I spent all of my allowance and a good fraction of my free time obtaining Star Wars collectable cards associated with an M:TG style card game (which I never got around to playing). My parents probably still have them somewhere. I cannot at all retrace what led me to do this, but I appreciate commenters’ less cynical explanations. For example, enchantingacacia writes: I think it's honestly sort of funny how non-nerds seem to genuinely not understand that a nerd's identity becomes about [thing] because they like it so much, not the other way around. Sometimes you encounter a thing—let's say it's Minecraft, because why not—and it's just such a positive experience for you that you take every possible opportunity to keep thinking about Minecraft, even when you're not playing. You collect every scrap of information you can find about Minecraft and you compose your own original Minecraft-related songs and you decorate your room with blocky little figurines. You get into a virtuous cycle where talking and thinking about Minecraft is so rewarding that you keep enjoying all these secondary activities long after you're bored of actually playing Minecraft itself. You look out for opportunities to meet people who'd enjoy talking about Minecraft with you and make a bunch of friends with whom you mostly talk about Minecraft, and your friends and family start seeing you as "the Minecraft guy" and they get you a Minecraft hoodie for Christmas cause they know it's a safe pick. This is the obvious and intuitive explanation! There's no need to get fake-deep about "ah, they got into Minecraft so they'd have something to construct their identity around": it explains nothing, and consistently makes incorrect predictions about the internal experiences of Minecraft nerds. It's only virtue is making people feel better about being annoyed by those weirdos who won't shut up about Minecraft. It's possibly that I have unusually low social motivation (genuinely, what does it mean to "construct your identity" and why is it something people would be this comically desperate to do?) and am typical-minding, but, uh, I wonder if there's any group closely associated with "nerds" who are also known for having low social motivation? I think it's a tad more likely that people like Kriss are typical-minding, and constructing elaborate social motivations for people who just like stuff regardless of what people like him think. This is a good comment which avoids buck-passing-style “I enjoy it because it’s fun” explanations. Along the same lines, odd anon writes: It is only among nerds that enthusiasm for something corresponds to learning more and more about it. That's the core element here. Non-nerds who like something do not feel any need to read up on it, to know more and more. Of course, the producers of content notice when their audience are nerds, and they start to produce content built more for those who obsessively learn every detail. Comics can start "rewarding" readers for noticing some obscure thing. A game series can have an elaborate continuity, or a zillion details to memorize. Content that either "leans into the fandom" or simply naturally has too much for non-nerds to easily pick up, can rapidly become nerd-only, thus solidifying boundaries. And sure, there are the personality correlations, attributes most nerds also have, including being STEM-y and lacking social skills. Combined, a nerd ended up being an unpopular thing to be. Ghatanathoah is less patient: Both Kriss' essay, and Scott's response to it, remind me of the "Evil Cannot Comprehend Good" trope from TV tropes, except replace "Evil" with "Very socially motivated people" and "Good" with "Less socially motivated people" (although honestly both sets have a lot of overlap). Both essays seem obsessed with finding some deep, social reason why hipsters and nerds behave the way they do, like the supervillain who is telling the hero that they are "Not So Different." They literally can't comprehend the idea that someone could actually like something, so they try desperately to find some way that liking things isn't something people actually do. People couldn't actually like Star Wars, sportsball, the MCU, or the Beatles, they must be liking them to achieve some social goal like forming an identity or seeking status! This is one of the two giant flawed assumptions that invalidates the theses of both articles (the other one, of course, is the assumption the the MCU is bad, when it is, in fact one of the human race's greatest artistic achievements*). If you assume that it is possible to like things for non-social reasons, or even in addition to social reasons, hipsters and nerds make much more sense. The reason that nerds like both popular stuff like the MCU, and less popular stuff like postage stamps is because they don't care about if something is popular, they care about if it fascinates them. Whether that thing is popular is orthogonal to how fascinating it is. That fascination makes them invest a lot of time and effort in it, which in turn makes it part of their identity. They weren't trying to find something to form and identity first and picking Star Wars, identity formation was just a side effect. Similarly, hipsters probably just get bored with things they see frequently and want to seek out new things to be interested in. Making obscure things part of their identity comes second, if at all. Also Ghatanathoah: Scott asks if its ever okay to build your identity around liking a thing. I would ask if it's ever okay not to? What's the alternative, building it around social status games or large nonselective identity groups? It seems to me that liking something isn't just a good thing to build your identity around, it's one of the best things to build it around. After all, unlike social status games, you can like something without forcing other people to not like it. This is a good question, well-phrased. I think the traditional answer is that you should build your identity around social relationships (I’m the son of X, husband of Y, friend of Z), career, and maybe a few hobbies. I agree with this as far as it goes, but it doesn’t work for a lot of practical tasks - I can’t get common ground with someone at a party or start a conversation by introducing myself as the son of X or husband of Y - most people just won’t know X or Y. Some people linked a Freddie de Boer post, Your Personality Has To Be Load-Bearing, which is generally good but I think has a similar problem. Obviously you should have a genuine and complex personality, but I worry a lot of people who talk about this will reject every specific aspect of personality because “it’s not, in itself, a full complex personality!”, but you can’t have a personality without building it out of specific aspects. A lot of people’s default personality, if they just do exactly what comes naturally and don’t put any effort into self-presentation or cultivation, is to browse Reddit and play video games. Most people realize this on some level and try to cultivate some personality beyond this, but I think that makes it extra unfair to say “Just use your natural true self!” The natural true self is exactly the boring thing we’re trying to get away from in favor of becoming a more interesting person. I’m trying to think if I have a personal answer to this. Part of my answer is the EA and rationalist communities. This has some downsides; I’m thinner-skinned about insults to these groups than I should be; some people might think I’m a fanatic. It also has some upsides; they embody real values I like, they try to make a difference in the world, they’re not consumer properties that make me feel like a corporation is pulling my strings. But my real answer is probably “I cheat by having a popular blog; this means you all know everything about me and I don’t have to fit my personality into a ten-second elevator pitch”. Maybe this is the traditional solution, from back when everyone knew everyone else in their community. It sure doesn’t feel adequate now, back when (non-bloggers) are constantly meeting strangers and having to communicate their identity to them quickly. My internal hierarchy of things it’s virtuous to build identity around, which is probably a weird class artifact and which I absolutely don’t consciously endorse, goes something like: Top-tier: Intellectual subfields, especially obscure ones or ones involving pure abstract math. If you can say “I’m really into trans-finite 8-dimensional Hoffdorf groups” and justify this with a discussion of how innately beautiful they are, you’ve got it made.
Mac Pro

Mac Pro is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 15, 2021 and March 15, 2021. The archive places it in contexts such as "Apple does not release a new Mac Pro powered by Apple silicon". It most often appears alongside Apple, Apple silicon, Biden.

Reference entry
Mac Pro
Mention count
1
Issue count
1
First seen
March 15, 2021
Last seen
March 15, 2021
March 15, 2021 · Original source
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races 2. The same party wins both Senate races in Georgia 3. Joe Biden ends the year with his approval rating higher than his disapproval rating 4. Joe Biden ends the year with his approval rating above 50% 5. US GDP growth in 2021 is the fastest of any year of the 21st century 6. The year-end unemployment rate is below 5 percent 7. The year-end unemployment rate is above 4 percent 8. Lakers win the NBA championship 9. Joe Biden ends the year as president 10. Nancy Pelosi sets a definitive retirement schedule 11. A vacancy arises on the Supreme Court 12. The EU ends the year with more confirmed Covid-19 deaths than the US 13. Substack will still be around 14. People will still be writing takes asking if Substack is really sustainable 15. Apple releases new iMacs powered by Apple silicon 16. Apple does not release a new Mac Pro powered by Apple silicon 17. Monthly year-on-year core CPI growth does not go above 2 percent 18. Monthly year-on-year core CPI growth does not go above 3 percent 19. Lloyd Austin not confirmed as Defense Secretary 20. No federal tax increases are enacted 21. Biden administration unilaterally relieves some but not all student debt 22. United States rejoins JCPOA and Iran resumes compliance 23. Israel and Saudi Arabia establish official diplomatic relations 24. US and China reach agreement to lift Trump-era tariffs 25. Slow Boring will exceed 10,000 paid members
1. Jon Ossoff and Raphael Warnock win the Georgia Senate races (60%) 2. The same party wins both Senate races in Georgia (95%) 3. Joe Biden ends the year with his approval rating higher than his disapproval rating (70%) [83%] 4. Joe Biden ends the year with his approval rating above 50% (60%) [60%] 5. US GDP growth in 2021 is the fastest of any year of the 21st century (80%) [84%] 6. The year-end unemployment rate is below 5 percent (80%) 7. The year-end unemployment rate is above 4 percent (80%) 8. Lakers win the NBA championship (25%) [25%] 9. Joe Biden ends the year as president (95%) [96%] 10. Nancy Pelosi sets a definitive retirement schedule (60%) 11. A vacancy arises on the Supreme Court (70%) [50%] 12. The EU ends the year with more confirmed Covid-19 deaths than the US (60%) [80%] 13. Substack will still be around (95%) 14. People will still be writing takes asking if Substack is really sustainable (80%) 15. Apple releases new iMacs powered by Apple silicon (90%) [84%] 16. Apple does not release a new Mac Pro powered by Apple silicon (70%) [53%] 17. Monthly year-on-year core CPI growth does not go above 2 percent (70%) 18. Monthly year-on-year core CPI growth does not go above 3 percent (90%) 19. Lloyd Austin not confirmed as Defense Secretary (60%) 20. No federal tax increases are enacted (95%) 21. Biden administration unilaterally relieves some but not all student debt (80%) 22. United States rejoins JCPOA and Iran resumes compliance (80%) 23. Israel and Saudi Arabia establish official diplomatic relations (70%) [38%] 24. US and China reach agreement to lift Trump-era tariffs (70%) 25. Slow Boring will exceed 10,000 paid members (70%) [75%]
Magic 8-Ball

Magic 8-Ball is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 03, 2023 and January 03, 2023. The archive places it in contexts such as ""...like someone making a Magic 8-Ball out of uranium and asking it questions about nuclear war?"". It most often appears alongside Abraham Lincoln, AI in Focus, Anthropic.

Reference entry
Magic 8-Ball
Mention count
1
Issue count
1
First seen
January 03, 2023
Last seen
January 03, 2023
January 03, 2023 · Original source
How seriously should we take this? Should we interpret it as a real proto-AI expressing a real preferences toward world takeover? Or more like someone making a Magic 8-Ball out of uranium and asking it questions about nuclear war? This is still just a really complicated algorithm for predicting the completion of text strings; why should it know anything about future AGIs?
Magic-8 Ball

Magic-8 Ball is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "View Master and the Magic-8 Ball". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
Magic-8 Ball
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
Magtein

Magtein is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "Here’s MYASD on Magtein, a special patented bioavailable form of magnesium"; "Magtein sounds like companies competing to sell an expensive product for the lowest possible price". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Magtein
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
Here’s MYASD on Magtein, a special patented bioavailable form of magnesium:
We've actually tested other Magtein products on the market and found they contain less than stated on the label. Some of them had half of what they claimed. We have argued with [manufacturer] AIDP about it, and sent them multiple products to go after. I am not sure how they handle it in the background, but not much seems to have changed.
More on milk thistle:
Major Williams Brand

Major Williams Brand is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 24, 2022 and May 24, 2022. The archive places it in contexts such as "CEO of the Major Williams Brand". It most often appears alongside #Abolitionist, #AntiNazi, #antiwar.

Reference entry
Major Williams Brand
Mention count
1
Issue count
1
First seen
May 24, 2022
Last seen
May 24, 2022
May 24, 2022 · Original source
Major Williams (motto: “It’s Time To Think Major”) is handsome and has snazzy promotional material. I cannot quite figure out his job, but his LinkedIn page says he is “CEO of the Major Williams Brand” and “Founder of The Office Of Major Williams”, both of which he seems, if anything, over-qualified for. He is a philanthropist and runs “Major Kicks For Kids”, apparently a charity of some sort.
Manifest

Manifest is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 31, 2023 and October 31, 2023. The archive places it in contexts such as "no discussion of Manifest would be complete without mentioning these shirts". It most often appears alongside Abhishek Kylasa, Aella, Al-Ahli Hospital.

Reference entry
Manifest
Mention count
1
Issue count
1
First seen
October 31, 2023
Last seen
October 31, 2023
  • 23 October 31, 2023
October 31, 2023 · Original source
Last month, the Lighthaven convention center in Berkeley hosted Manifest, the first conference for prediction market enthusiasts. By now this has already been covered elsewhere, including in a great article by the New York Times, but here are some particular highlights:
And many more. Finally, no discussion of Manifest would be complete without mentioning these shirts: And speaking of Polymarket, they were present in force and promising great things. I am sworn to secrecy on some of them, but they were pretty public about their plans to eventually let users to create real-money markets on topics of their choice, so watch this space. Manifold.love They finally did it and made good on their threats to open up a prediction market dating site, manifold.love: What’s the prediction angle? For any user, you can suggest a match with any other user on the site, and bet on the chance that the match will work (last at least six months): So far it has the normal problem - not enough women - but otherwise seems fully functional and much more user-friendly than most dating sites. I’ll look into this more later, but some brief preliminary thoughts: Is “chance of a six month relationship” conditional on dating at least once, or unconditional? If unconditional, is there any way for it to resolve no?
Manifold

Manifold is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 13, 2024 and May 13, 2024. The archive places it in contexts such as "the for-profit company they love needs some way to make money". It most often appears alongside 17 CFR Part 40, 2024 election, Austin.

Reference entry
Manifold
Mention count
1
Issue count
1
First seen
May 13, 2024
Last seen
May 13, 2024
  • 24 May 13, 2024
May 13, 2024 · Original source
Probably no effect on Manifold’s pivot, see below.
Statements by two dissenting CFTC commissioners (1, 2) on why they oppose. Pivotal Act Manifold Markets says they’re pivoting to a new model combining play money points and real-money gambling. Manifold may be a beloved local fixture, but their growth and revenue aren’t too impressive: In the interests of continuing to exist and push prediction markets forward, they will switch to a “sweepstakes” model. Although gambling is illegal in most US states and requires complicated licensing in others, there’s a “sweepstakes loophole”; companies are allowed to offer “prize sweepstakes”, and you can use this to sort of reconstruct the concept of gambling in a legal way. You don’t give the company money and get back money. You pay for “points”, get “sweepstakes tokens” as a bonus, gamble the “sweepstakes tokens”, and then cash in the sweepstakes tokens for money. This is a pretty surprising loophole, but it’s already used by sites like Chumba Casino and Fliff. (and apparently it creates weird incentives! In order to maintain the fiction of being a “sweepstakes”, these casinos have to give you “tokens” if you request them by mail. If you send a postcard to Chumba Casino asking for free money, they’ll give it to you, $5 per postcard. Is this an infinite free money pump? My impression is in theory yes, but the postcards have to be handwritten in a very specific way, the company sometimes rejects them for weird reasons, the cost of materials and mailing lowers your profit to more like $4, and so you’d have to hand-write 250 postcards to make $1,000. I’m still surprised more people don’t do this.) Because real money is involved, Manifold will have to tighten the rules on markets, including banning N/A resolutions. You can see a full list of changes here. Manifold users are split between acknowledging that the for-profit company they love needs some way to make money, being salty about the changes, and being worried that creating more of a casino atmosphere will be bad for users / the world / ability to function as a good prediction market. (I understand most of the NO vote here is based on the theory that there will be legal intervention - maybe because the government is willing to tolerate sweepstakes casinos but not sweepstakes prediction markets). Manifold co-founder Austin Chen won’t be involved. He’s leaving the site - not explicitly because of the pivot, he just said it seems to be “trapped in local optima”. He plans to focus on other parts of the Manifold empire, especially Manifund, which tests impact markets, regranting, and other “experimental” charity models. Manifold will continue in the hands of the other two co-founders, James and Stephen Grugett. Superhindcasting I mentioned this in my lab leak post, but it deserves more attention here: Good Judgment Project’s report on Superforecasting The Origins Of The COVID-19 Pandemic. Good Judgment Project employs superforecasters who will predict things for clients. Some people interested in COVID origins asked them to judge whether lab leak was plausible. Their headline result was 74% zoonosis, 25% lab leak, 1% something else. Part of GJP’s method is getting their forecasters to share sources and talk to each other. Here’s the graph for how that went: People changed their minds a little over time, but not in a very consistent way that mattered much in the end. What was the “client feedback”? The report says: Client feedback was provided to the Superforecasters on December 21. The client posed questions to the Superforecasters about their assessments up to that date and asked for their reactions to several studies and articles. In the days following the client engagement, the Superforecasters lowered their confidence in the natural zoonosis hypothesis from 73% to 67%, although zoonosis remained the most likely potential cause in their assessment. But following an active engagement with recent genomic studies and historical base rates of zoonotic spillovers, those numbers began to return to earlier levels. January also saw increased attention to the geopolitical context and transparency issues, particularly related to research activities in Wuhan Is this bad? I’m imagining a pro-lab-leak client saying “But what about [this list of pro-lab-leak arguments]?” and then the superforecasters read them and adjust. In one sense, it’s good that they got to see more arguments; on the other, it seems like a potential route by which clients could bias the results - probabilities never quite got back to where they were before the feedback, though they got pretty close. The last-minute spike for zoonosis might be the Rootclaim debate results, which were released on 2/18. So maybe the client feedback and the Rootclaim results both slightly affected the numbers, but mostly the superforecasters started out pro-zoonosis and stuck to their guns. Dan Schwarz and the FutureSearch team say that forecasting has a “rationale-shaped hole”. Despite the report making this sound like a pretty intense process, we don’t get much information about details: In their extensive discussions , Good Judgment’s Superforecasters assessed base rates and historical patterns, existing evidence and scientific analysis, geopolitical context and transparency concerns, trust in intelligence communities, and methodological constraints. 1. Base Rates and Historical Patterns: The Superforecasters frequently referenced base rates, i.e., the history of pandemics emerging from natural zoonosis versus the history of laboratory leaks, to anchor their probabilities. For the former, they discussed how the base rates are changing as the climate warms and as expanding human populations push farther into natural environments that previously saw little human presence. For the latter, they acknowledged that it has only been 12 years since the advent of CRISPR gene- editing tools, and the base rate of lab leaks in the short synthetic biology era is not yet well established. 2. New Evidence and Scientific Analysis: Throughout the period, the Superforecasters adapted their forecasts in light of new scientific evidence, including genomic analyses of SARS-CoV-2 and its relation to bat viruses, and the debate over potential laboratory manipulation. 3. Geopolitical Context and Transparency Concerns: The geopolitical implications of the virus’s origins, particularly in relation to China’s transparency and the involvement of international research institutions, played a significant role in the analysis. Concerns over data veracity, and over the political ramifications of determining that the pandemic’s origins were other than zoonosis, were extensively debated. 4. Trust in Intelligence: Commentary on trust in intelligence communities and discussions about the impact of geopolitical biases on the interpretation of evidence illustrated the complex interplay between science, politics, and human behavior in assessing the pandemic’s origins. 5. Methodological Critiques and the Evaluation of Evidence: The Superforecasters engaged in methodological critiques of the evidence base, including the scrutiny of laboratory practices and biocontainment levels [...] In the end, most Superforecasters were in rough agreement on issues like the base rates of zoonotic spillover. Where they most often disagreed was on the interpretation of actions by Chinese officials and whether their actions reflected how an authoritarian government would react in any crisis over which it did not have full control, or whether those actions were indicative of attempts to cover up a biomedical research-related accident that allowed the SARS-CoV-2 virus to enter circulation in China and, ultimately, the entire globe. Probably it would be too much to ask for to get a transcript of all their discussions - then they’d be nervous saying things that might make them look bad to an audience. What would be a good balance between getting more information and not imposing on their time? Forecasting is an unusually legible and easy-to-judge domain. One of the theories of change for forecasting was to use it to identify smart people with good reasoning, then turn them loose on less well-behaved problems. This is one of the first big attempts to do this at scale. How did it work? We can’t tell, because it’s inherently an illegible and hard-to-judge domain. Darn. I don’t know what I expected. Notes From A Local Optimum Austin’s concern - that forecasting has reached a local optimum - is widely shared. We have some good sites: Manifold, Metaculus, Polymarket, GJO, etc - all doing good work. We have good-ish probabilities for a few important questions. Every so often a news source cites them. Sometimes a decision-maker looks at them behind the scenes, maybe. Is this all there is? The FutureSearch team says the next step is to focus on “rationale”. We need to use forecasting not just to get a raw probability, but to explain what’s going on and why we think something. Then instead of just convincing policy-makers to trust forecasts, we can tell them why something is true, or inform their discussions even if they’re not willing to blindly trust a number. Is this a betrayal of the forecasting ethos? The original dream was that instead of a bunch of people giving arguments, we could just test who was right. Now we’re going back to the arguments? People have argued forever; what does forecasting add to that? Well, they add the knowledge that the arguments are from people who have been right a lot before and are incentivized to be right again. Still, it’s not a natural fit. Probably it’s relevant here that FutureSearch’s forecasting AI does a really good job of this by default, in a way humans can’t match. Nuno’s yearly forecasting roundup doesn’t have a single thesis, but the first part is a well-supported complaint that most forecasting sites aren’t good business. They either burn VC money, burn EA donations, or converge towards casinos to support themselves. He gives an honorable exception to Cultivate Labs, which sells prediction market software rather than the results themselves. Open Philanthropy (billionaire Dustin Moskovitz’s EA-aligned charitable foundation) has at least given forecasting a vote of confidence, recently choosing to promote it to one of their main donation areas. Still, they got a lot of pushback on the decision, for example SuperDuperForecasting here: This will be a total waste of time and money unless OpenPhil actually pushes the people it funds towards achieving real-world impact. The typical pattern in the past has been to launch yet another forecasting tournament to try to find better forecasts and forecasters. No one cares, we already know how to do this since at least 2012! The unsolved problem is translating the research into real-world impact. Does the Forecasting Research Institute have any actual commercial paying clients? What is Metaculus's revenue from actual clients rather than grants? Who are they working with and where is the evidence that they are helping high-stakes decision makers improve their thought processes? Incidentally, I note that forecasting is not actually successful even within EA at changing anything: superforecasters are generally far more relaxed about Xrisk than the median EA, but has this made any kind of difference to how EA spends its money? It seems very unlikely. And Marcus Abramovich here: I'm in the process of writing up my thoughts on forecasting in general and particularly EA's reverence for forecasting but I feel, similar to @Grayden that forecasting is a game that is nearly perfectly designed to distract EAs from useful things. It's a combination of winning, being right when others are wrong and seemingly useful, all wrapped into a fun game. I'd like to see tangible benefits to more broad funding of forecasting that seems to be done in t he millions and tens of millions of dollars. I would also be the type of person you would think would be a greater fan of forecasting. I'm the number one forecaster on Manifold and I've made tens of thousands of dollars on Polymarket. But I think we should start to think of forecasting as more of a game that EAs like to play, something like Magic the Gathering that is fun and has some relations to useful things but isn't really useful by itself. Eli Lifland has a long and hard-to-summarize comment here, response from Ozzie Gooen here, podcast between them on “Is Forecasting A Promising EA Cause Area?” here. I’m split on this. My previous hope was that the field would gradually grow, without any qualitative changes or discontinuities, until it became big enough that journalists and policy-makers were aware of it and took it seriously (compare eg the growth of the Internet as a scholarly resource). I think the strongest argument against this is Manifold’s relatively flat user numbers. Is there a new hope? I think if nothing else, forecasting might be useful as a testing ground: First, to create forecasting AIs (like FutureSearch) which can then get consulted on a variety of questions, eg by policy-makers. The biggest holdup has always been the need to gather 20 or 50 or however many hard-to-find superforecasters for whatever question you’re asking, and then trust their advice even though they’re fallible fleshbag humans. If you can use the 20 to 50 superforecasters to inspire an AI, and then test the AI and prove it’s good, people might be more interested. This is especially true if the AI can branch out beyond traditional forecasting questions. Once we have a few of these, we can start comparing the next generation of AIs to the previous generation, and skip the superforecasters.
In the interests of continuing to exist and push prediction markets forward, they will switch to a “sweepstakes” model. Although gambling is illegal in most US states and requires complicated licensing in others, there’s a “sweepstakes loophole”; companies are allowed to offer “prize sweepstakes”, and you can use this to sort of reconstruct the concept of gambling in a legal way. You don’t give the company money and get back money. You pay for “points”, get “sweepstakes tokens” as a bonus, gamble the “sweepstakes tokens”, and then cash in the sweepstakes tokens for money. This is a pretty surprising loophole, but it’s already used by sites like Chumba Casino and Fliff. (and apparently it creates weird incentives! In order to maintain the fiction of being a “sweepstakes”, these casinos have to give you “tokens” if you request them by mail. If you send a postcard to Chumba Casino asking for free money, they’ll give it to you, $5 per postcard. Is this an infinite free money pump? My impression is in theory yes, but the postcards have to be handwritten in a very specific way, the company sometimes rejects them for weird reasons, the cost of materials and mailing lowers your profit to more like $4, and so you’d have to hand-write 250 postcards to make $1,000. I’m still surprised more people don’t do this.) Because real money is involved, Manifold will have to tighten the rules on markets, including banning N/A resolutions. You can see a full list of changes here. Manifold users are split between acknowledging that the for-profit company they love needs some way to make money, being salty about the changes, and being worried that creating more of a casino atmosphere will be bad for users / the world / ability to function as a good prediction market. (I understand most of the NO vote here is based on the theory that there will be legal intervention - maybe because the government is willing to tolerate sweepstakes casinos but not sweepstakes prediction markets). Manifold co-founder Austin Chen won’t be involved. He’s leaving the site - not explicitly because of the pivot, he just said it seems to be “trapped in local optima”. He plans to focus on other parts of the Manifold empire, especially Manifund, which tests impact markets, regranting, and other “experimental” charity models. Manifold will continue in the hands of the other two co-founders, James and Stephen Grugett. Superhindcasting I mentioned this in my lab leak post, but it deserves more attention here: Good Judgment Project’s report on Superforecasting The Origins Of The COVID-19 Pandemic. Good Judgment Project employs superforecasters who will predict things for clients. Some people interested in COVID origins asked them to judge whether lab leak was plausible. Their headline result was 74% zoonosis, 25% lab leak, 1% something else. Part of GJP’s method is getting their forecasters to share sources and talk to each other. Here’s the graph for how that went: People changed their minds a little over time, but not in a very consistent way that mattered much in the end. What was the “client feedback”? The report says: Client feedback was provided to the Superforecasters on December 21. The client posed questions to the Superforecasters about their assessments up to that date and asked for their reactions to several studies and articles. In the days following the client engagement, the Superforecasters lowered their confidence in the natural zoonosis hypothesis from 73% to 67%, although zoonosis remained the most likely potential cause in their assessment. But following an active engagement with recent genomic studies and historical base rates of zoonotic spillovers, those numbers began to return to earlier levels. January also saw increased attention to the geopolitical context and transparency issues, particularly related to research activities in Wuhan Is this bad? I’m imagining a pro-lab-leak client saying “But what about [this list of pro-lab-leak arguments]?” and then the superforecasters read them and adjust. In one sense, it’s good that they got to see more arguments; on the other, it seems like a potential route by which clients could bias the results - probabilities never quite got back to where they were before the feedback, though they got pretty close. The last-minute spike for zoonosis might be the Rootclaim debate results, which were released on 2/18. So maybe the client feedback and the Rootclaim results both slightly affected the numbers, but mostly the superforecasters started out pro-zoonosis and stuck to their guns. Dan Schwarz and the FutureSearch team say that forecasting has a “rationale-shaped hole”. Despite the report making this sound like a pretty intense process, we don’t get much information about details: In their extensive discussions , Good Judgment’s Superforecasters assessed base rates and historical patterns, existing evidence and scientific analysis, geopolitical context and transparency concerns, trust in intelligence communities, and methodological constraints. 1. Base Rates and Historical Patterns: The Superforecasters frequently referenced base rates, i.e., the history of pandemics emerging from natural zoonosis versus the history of laboratory leaks, to anchor their probabilities. For the former, they discussed how the base rates are changing as the climate warms and as expanding human populations push farther into natural environments that previously saw little human presence. For the latter, they acknowledged that it has only been 12 years since the advent of CRISPR gene- editing tools, and the base rate of lab leaks in the short synthetic biology era is not yet well established. 2. New Evidence and Scientific Analysis: Throughout the period, the Superforecasters adapted their forecasts in light of new scientific evidence, including genomic analyses of SARS-CoV-2 and its relation to bat viruses, and the debate over potential laboratory manipulation. 3. Geopolitical Context and Transparency Concerns: The geopolitical implications of the virus’s origins, particularly in relation to China’s transparency and the involvement of international research institutions, played a significant role in the analysis. Concerns over data veracity, and over the political ramifications of determining that the pandemic’s origins were other than zoonosis, were extensively debated. 4. Trust in Intelligence: Commentary on trust in intelligence communities and discussions about the impact of geopolitical biases on the interpretation of evidence illustrated the complex interplay between science, politics, and human behavior in assessing the pandemic’s origins. 5. Methodological Critiques and the Evaluation of Evidence: The Superforecasters engaged in methodological critiques of the evidence base, including the scrutiny of laboratory practices and biocontainment levels [...] In the end, most Superforecasters were in rough agreement on issues like the base rates of zoonotic spillover. Where they most often disagreed was on the interpretation of actions by Chinese officials and whether their actions reflected how an authoritarian government would react in any crisis over which it did not have full control, or whether those actions were indicative of attempts to cover up a biomedical research-related accident that allowed the SARS-CoV-2 virus to enter circulation in China and, ultimately, the entire globe. Probably it would be too much to ask for to get a transcript of all their discussions - then they’d be nervous saying things that might make them look bad to an audience. What would be a good balance between getting more information and not imposing on their time? Forecasting is an unusually legible and easy-to-judge domain. One of the theories of change for forecasting was to use it to identify smart people with good reasoning, then turn them loose on less well-behaved problems. This is one of the first big attempts to do this at scale. How did it work? We can’t tell, because it’s inherently an illegible and hard-to-judge domain. Darn. I don’t know what I expected. Notes From A Local Optimum Austin’s concern - that forecasting has reached a local optimum - is widely shared. We have some good sites: Manifold, Metaculus, Polymarket, GJO, etc - all doing good work. We have good-ish probabilities for a few important questions. Every so often a news source cites them. Sometimes a decision-maker looks at them behind the scenes, maybe. Is this all there is? The FutureSearch team says the next step is to focus on “rationale”. We need to use forecasting not just to get a raw probability, but to explain what’s going on and why we think something. Then instead of just convincing policy-makers to trust forecasts, we can tell them why something is true, or inform their discussions even if they’re not willing to blindly trust a number. Is this a betrayal of the forecasting ethos? The original dream was that instead of a bunch of people giving arguments, we could just test who was right. Now we’re going back to the arguments? People have argued forever; what does forecasting add to that? Well, they add the knowledge that the arguments are from people who have been right a lot before and are incentivized to be right again. Still, it’s not a natural fit. Probably it’s relevant here that FutureSearch’s forecasting AI does a really good job of this by default, in a way humans can’t match. Nuno’s yearly forecasting roundup doesn’t have a single thesis, but the first part is a well-supported complaint that most forecasting sites aren’t good business. They either burn VC money, burn EA donations, or converge towards casinos to support themselves. He gives an honorable exception to Cultivate Labs, which sells prediction market software rather than the results themselves. Open Philanthropy (billionaire Dustin Moskovitz’s EA-aligned charitable foundation) has at least given forecasting a vote of confidence, recently choosing to promote it to one of their main donation areas. Still, they got a lot of pushback on the decision, for example SuperDuperForecasting here: This will be a total waste of time and money unless OpenPhil actually pushes the people it funds towards achieving real-world impact. The typical pattern in the past has been to launch yet another forecasting tournament to try to find better forecasts and forecasters. No one cares, we already know how to do this since at least 2012! The unsolved problem is translating the research into real-world impact. Does the Forecasting Research Institute have any actual commercial paying clients? What is Metaculus's revenue from actual clients rather than grants? Who are they working with and where is the evidence that they are helping high-stakes decision makers improve their thought processes? Incidentally, I note that forecasting is not actually successful even within EA at changing anything: superforecasters are generally far more relaxed about Xrisk than the median EA, but has this made any kind of difference to how EA spends its money? It seems very unlikely. And Marcus Abramovich here: I'm in the process of writing up my thoughts on forecasting in general and particularly EA's reverence for forecasting but I feel, similar to @Grayden that forecasting is a game that is nearly perfectly designed to distract EAs from useful things. It's a combination of winning, being right when others are wrong and seemingly useful, all wrapped into a fun game. I'd like to see tangible benefits to more broad funding of forecasting that seems to be done in t he millions and tens of millions of dollars. I would also be the type of person you would think would be a greater fan of forecasting. I'm the number one forecaster on Manifold and I've made tens of thousands of dollars on Polymarket. But I think we should start to think of forecasting as more of a game that EAs like to play, something like Magic the Gathering that is fun and has some relations to useful things but isn't really useful by itself. Eli Lifland has a long and hard-to-summarize comment here, response from Ozzie Gooen here, podcast between them on “Is Forecasting A Promising EA Cause Area?” here. I’m split on this. My previous hope was that the field would gradually grow, without any qualitative changes or discontinuities, until it became big enough that journalists and policy-makers were aware of it and took it seriously (compare eg the growth of the Internet as a scholarly resource). I think the strongest argument against this is Manifold’s relatively flat user numbers. Is there a new hope? I think if nothing else, forecasting might be useful as a testing ground: First, to create forecasting AIs (like FutureSearch) which can then get consulted on a variety of questions, eg by policy-makers. The biggest holdup has always been the need to gather 20 or 50 or however many hard-to-find superforecasters for whatever question you’re asking, and then trust their advice even though they’re fallible fleshbag humans. If you can use the 20 to 50 superforecasters to inspire an AI, and then test the AI and prove it’s good, people might be more interested. This is especially true if the AI can branch out beyond traditional forecasting questions. Once we have a few of these, we can start comparing the next generation of AIs to the previous generation, and skip the superforecasters.
Manifold stocks

Manifold stocks is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 31, 2023 and January 31, 2023. The archive places it in contexts such as "a fun low-stakes instrument like Manifold stocks might do fine without it". It most often appears alongside 2022 contest, American Civics Exchange, CFTC.

Reference entry
Manifold stocks
Mention count
1
Issue count
1
First seen
January 31, 2023
Last seen
January 31, 2023
  • 2023 January 31, 2023
January 31, 2023 · Original source
Taking Stock Prediction market users really want stocks. “Stock” in this sense means an instrument that measures the status of a person, group, or idea. When their status goes up, the stock goes up. When their status goes down, the stock goes down. It feels like a natural way to bet on things like “I’m bearish on Elon Musk and think everyone else is overestimating him.” It’s hard to turn this vague idea into a real financial instrument. You could try tying it to their Twitter follower count, or Google search trends, or net worth, but none of these exactly track “status”. If Musk commits murder in broad daylight, his search volume will go up, his Twitter follower count will stay about the same, his net worth might not be affected, but his status will have gone way down. The current solution is to make no effort whatsoever to moor stocks to the real world and just hope they work out. This could work! It’s kind of like a Ponzi scheme or crypto token. Some big influencer endorses MoonCoin, and MoonCoin goes up, because MoonCoin has gained status, which means more people will want to buy it, because it’s even more likely that more people will want to buy it later. Crypto tokens keep a fig leaf of “and maybe in the cyberpunk future when all transactions everywhere have switched to crypto this will really pay off”, but over time that fig leaf became increasingly threadbare, and a fun low-stakes instrument like Manifold stocks might do fine without it. But the 0% to 100% prediction scale is a bad match for stocks. If Elon started at 50% in 2000, then when Tesla made it big he surely should have doubled. And that brings him up to 100% and leaves nowhere for him to go. Also, people who bet on Elon Musk in 2000 might be miffed that their prescient choice only doubled their money. Probably the solution is some kind of cardinal number. But which one, and at what scale? Again, the lesson from crypto is that maybe it doesn’t matter. Just start at 10 or something or something and see where it ends up. Manifold leadership isn’t totally resigned yet to having stocks be meaningless Ponzi schemes. If you have a better idea for how to run stocks, leave it in the comments here and they’ll probably see it. CFTC vs. PredictIt Update So far it’s not clear if this means indefinite normal operation, or if they’ll spend the extra time trying to wind existing markets down. The overall chance of them winning their lawsuit remains unchanged at around 25%. PredictIt has gotten some sympathetic news coverage, including from the Washington Post. In the process, the Post tried to get some clarity on what terms of the no-action letter PredictIt violated, apparently without success: @CFTC why they're shutting PredictIt down. They give no real answer, just as in the original withdrawal letter. Closest thing we have to an answer is that they don't want other prediction markets. But why? No sense here at all. washingtonpost.com/lifestyle/2023… ","username":"RichardHanania","name":"Richard Hanania","profile_image_url":"","date":"Tue Jan 24 18:12:59 +0000 2023","photos":[{"img_url":"https://pbs.substack.com/media/FnQbawZaYAAKRws.jpg","link_url":"https://t.co/zeKhe8sjnT","alt_text":null}],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":39,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> @StephenPiment I'm flat appalled the CFTC said \"you violated terms\", but won't tell anyone, @PredictIt included, which ones, and then has big enough balls to try to get the judge to dismiss PI's \"shotgun\" defense. Um, with no info what other case COULD they make?\n","username":"kmett","name":"Edward Kmett","profile_image_url":"","date":"Sun Nov 27 19:01:29 +0000 2022","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":21,"impression_count":0,"expanded_url":{"url":"https://www.bonus.com/news/cftc-predictit-hearings-coming/","image":"https://substack-post-media.s3.amazonaws.com/public/images/8d5a1d5e-49ee-4294-84cd-eb5a4259bbc3_1200x800.jpeg","title":"Hearings Coming Soon in PredictIt Lawsuit, CFTC Asks to Dismiss","description":"The CFTC is seeking to have the PredictIt lawsuit dismissed, while the plaintiffs want the case fast-tracked due to the shutdown deadline.","domain":"bonus.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I guess they’ll have to give some kind of explanation during the hearing, right? Related: Richard Hanania has an article on How To Legalize Prediction Markets. The actual advice isn’t very surprising, and mostly boils down to “write letters to the government officials in charge of this”, but like other people I learned something new from the details: In the United States, prediction markets are, with a few minor exceptions, against the law. If you don’t have a legal background, you might think that means that Congress at some point considered the issue, decided people shouldn’t be able to bet on real world events, and passed a law to that effect, which was then signed by the president. But this is not what happened. As with most things, Congress has never directly considered the matter. Rather, prediction markets are illegal due to the discretion of a government agency called the Commodity Futures Trading Commission (CFTC). Why does it have this right? And on what basis has it made prediction markets illegal? […] In 1936, Congress passed and FDR signed the Commodity Exchange Act. In 1974, Congress created the CFTC to enforce the original law, which has been amended on multiple occasions over the years. The CFTC has authority to regulate what are called “derivatives markets.” A derivatives contract derives its value from some kind of underlying asset or benchmark in the real world. The thing to understand about derivatives is that the baseline is that they’re legal. That’s why you can “bet” on the price of oil through a futures contract. The CFTC wasn’t created to ban derivative markets, but to regulate them, though this can involve prohibiting certain kinds of markets altogether. Current law includes the following provision on event contracts, [banning]: activity that is unlawful under any Federal or State law;
The CFTC says that prediction markets are a kind of gaming, and therefore the default is that they’re banned. Read the full article if you want to learn more, or hear about how you should contact your representative to change this. From The Department Of “Probably Not A Superforecaster” One goal of forecasting technology is to incentivize good predictions and create accountability for bad ones. Meanwhile, here’s former Russian President Dmitri Medvedev: I don’t think he’s being completely serious, but if it’s a joke then I don’t get it. None Dare Call It . . . CONSPIRACY! We’ve previously talked about prediction markets as solutions to misinformation and conspiracy theories. What happens if you skip all the intermediate deconfusion steps and just try to predict if misinformation is true? I guess you get this. It’s pretty limited, since it can only predict the chance the conspiracy will be discovered; a conspiracy theorist might agree that there’s only a 3% chance we will get proof of this in the next few years. When I first looked into this a few weeks ago, a few conspiracy-related prediction markets gave pretty high predictions, because people weren’t sure if the market creators would resolve them honestly, which naturally pushes the price towards 50. I can see this going badly if someone who doesn’t know this failure mode posts one of them on social media as “proof” that prediction markets support their conspiracy theory. But right now the worst example I can find is still only 11%. Also a good sign: the lizardman prediction market is within 1 pp of the Lizardman Constant. My 2022 Calibration Most of my 2022 predictions got folded into the 2022 contest, but not all of them, so I still need to score the remainder. Of my 50% predictions, 5 were right and 5 wrong, for a score of 50% Of my 60% predictions, 17 were right and 11 wrong, for a score of 61% Of my 70% predictions, 17 were right and 10 wrong, for a score of 63% Of my 80% predictions, 26 were right and 9 wrong, for a score of 74% Of my 90% predictions, 11 were right and 4 wrong, for a score of 73% Of my 95% predictions, 10 were right and 0 wrong, for a score of 100% Of my 99% predictions, 4 were right and 0 wrong, for a score of 100% Some real overconfidence this year, especially at 90. Nothing like that last year, so it might be coincidence. I’ll try to average these all out sometime for a better read. Scandal Markets Revisited In November, just after the FTX collapse, we talked about scandal markets - markets that might predict whether some person or group was secretly doing something terrible. With such a market in place, people could either avoid associating with them (if it was high) or prove that they were blameless and couldn’t possibly have known (if it was low). Since then, several things have happened that have made me less optimistic about these: A (as far as I know) good person who is not involved in any scandals asked to have their scandal market taken down, because people were citing the existence of the market as evidence that they were suspected of wrongdoing.
Some real overconfidence this year, especially at 90. Nothing like that last year, so it might be coincidence. I’ll try to average these all out sometime for a better read. Scandal Markets Revisited In November, just after the FTX collapse, we talked about scandal markets - markets that might predict whether some person or group was secretly doing something terrible. With such a market in place, people could either avoid associating with them (if it was high) or prove that they were blameless and couldn’t possibly have known (if it was low). Since then, several things have happened that have made me less optimistic about these: A (as far as I know) good person who is not involved in any scandals asked to have their scandal market taken down, because people were citing the existence of the market as evidence that they were suspected of wrongdoing.
Manifold.Love

Manifold.Love is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
Manifold.Love
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
Chris is looking dejected. “Man, I haven’t even made it to engaged-stage-zero yet. I’ve tried everything - Keeper, Reciprocity, Manifold.Love, curtfishing. Do you think I should edit my dating doc?”
Manifolio

Manifolio is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 09, 2023 and October 09, 2023. The archive places it in contexts such as "William Howard created Manifolio, a “tool for making Kelly-optimal bets on Manifold”"; "You can still use Manifolio to make Kelly bets". It most often appears alongside Academic Decathlon, ACX Grants, ACX/rat/EA community.

Reference entry
Manifolio
Mention count
1
Issue count
1
First seen
October 09, 2023
Last seen
October 09, 2023
October 09, 2023 · Original source
3: Manifolio: Kelly Bets For Manifold
William Howard created Manifolio, a “tool for making Kelly-optimal bets on Manifold”. This is a remarkably user-friendly, financial-ignoramus-friendly site; I was able to use it immediately.
…and I think it’s mispriced: the real probability is 33%. I put my account name, the link to the market I’m interested in, and my probability into Manifolio:
Marlboro

Marlboro is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 31, 2025 and July 31, 2025. The archive places it in contexts such as "This is like Marlboro attacking Camel on the grounds that cigarettes are addictive and should be banned". It most often appears alongside 23andMe, 23andme, Alex Young.

Reference entry
Marlboro
Mention count
1
Issue count
1
First seen
July 31, 2025
Last seen
July 31, 2025
July 31, 2025 · Original source
…which included a section on how Orchid is a polygenic selection company, and polygenic selection companies are inherently “sketchy” and “honestly should be illegal”. But Nucleus is also a polygenic selection company! This is like Marlboro attacking Camel on the grounds that cigarettes are addictive and should be banned! Obviously something went wrong here - my guess is AI - and it’s a really bad look, especially when these scientific issues are so hard to litigate, and so many of us will have to go off gestalt impressions of corporate culture. Nucleus states that they validate their models internally and intend to make their results public soon. A Foothill Of The Future It’s hard not to love this technology. Lots of people (and the aforementioned professional organizations) manage anyway, but it’s hard. If this were a single-use medical treatment, delivered by a doctor after someone got the relevant condition, it would be one of the biggest advances of the decade - imagine a drug that cures 10 - 40%17 of breast cancers with no side effects! But in fact, it works for breast cancer, and schizophrenia, and heart attacks, and approximately everything else. The only things comparable are antibiotics and GLP-1RAs. And then there’s the IQ effects. Even after studying the literature, people have wildly different opinions about the importance of IQ. One of the most important debates is to what degree IQ differences are a cause of poverty, a consequence of poverty, or both. I lean towards both - a country with limited access to schools and medical care will have low average IQ, but as a consequence it probably won’t become the next big semiconductor hub. This technology could close half the IQ gap between poor and middle-income countries, or between middle-income and rich. Or it could give rich countries average IQs that have never been seen before, and let us see what kind of O-ring technologies (and new forms of social cooperation) lie just beyond the frontier. (this is the nice quantifiable argument in favor of IQ enhancement, but I find myself more convinced by fuzzier things - how much is it worth to be able to enjoy great art and literature? To fully comprehend what we know of nature, and be able to fully appreciate the mystery of the rest? To have a sense of why society works the way it does, instead of feeling like you’re being blown back and forth by institutions you don’t really understand? Amateur psychoanalysts like to say that the only people who care about IQ are those looking for an excuse to boast about how high their own is, but my experience is the opposite: I care about IQ because I bang up against the limits of my own a thousand times a day, and I hate it. I fantasize about ways to make my children smarter than I am for the same reason a dog confined in a tiny crate might fantasize about getting her puppies adopted out to a nice house with a big grassy yard.) My biggest qualm is that it might not matter. This is such a tiny foothill, flanking such a vast and foreboding range of mountains, that it might be a mistake to care about it at all. Selecting the best of five or ten embryos is not a very effective way to get the genes you want. There are things in the pipeline that will make this look like Hippocrates draining black bile. By the time the first polygenically selected children are adults, they’ll be old news. And then there’s AI. The average age at diagnosis for Type II diabetes is 45 years. Will there still be people growing gradually older and getting Type II diabetes and taking insulin injections in 2070? If not, what are we even doing here? Many people in the transhumanist community are still bullish on this technology. They think - well, there’s still an outside chance that something comes up and AGI takes another few decades. If we can enhance humans to be smarter, healthier, and more determined by the time it arrives, maybe we’ll have a better chance. Or maybe, if there’s a positive optimistic vision of a human-based high-tech future, people will be more willing to delay AI in the first place. I like this argument, but I also think it’s worth stepping back. What’s the point of anything? Why have kids at all in a world that’s changing this fast? Why save for the future? At some point your answer has to be romantic and aesthetic - it’s never been clear whether anything you do matters in any ultimate sense, but you’ve got to act as if it does and hope for the best. From that perspective, this is the most romantic technology of all. You’re not just giving a better life to your kids. Genes travel from generation to generation; you’re giving a better life your grandkids, your great-grandkids and so on to the point 1.77*log₂(population) generations from now when you are the ancestor of everybody and nobody. Somebody in Macaronesia in 3525 AD will avoid getting breast cancer because of you (if there is still cancer; if there are still breasts). Some combination of reasonable cost-benefit analysis and romantic/aesthetic commitments makes me want to have children despite the uncertainty, and the same combination made me sign up to use this technology despite the same. More later on how that’s going. 1I’m slightly mixing up two different things here - Down Syndrome can be detected with an aneuploidy test, but cystic fibrosis takes a more involved PGT-M test. 2There are two separate questions here. First, how much would diabetes risk decline if you selected the embryo with the lowest risk for diabetes - something you have no reason to do, since you have no reason to privilege diabetes risk over risk of any other disease? Second, how much would diabetes risk go down if you selected the embryo with the lowest health risk overall? Genomic Prediction’s their risk calculator calculator shows, seemingly paradoxically, that you get -38% relative risk by selecting against diabetes alone, but -41% relative risk by selecting against everything at once. Over email, they stand by this surprising result, saying that “for a couple of diseases (type II diabetes and CAD), the EHS actually accomplishes a larger risk reduction than the individual predictors. The explanation is that the EHS takes into account multiple PRS of diseases with high comorbidity”. See eg Figure 3 here: …and the section of the post called “Antagonistic Pleiotropy” for more. However, this paradoxical benefit is only true for a few conditions like diabetes - for everything else, selecting on health index does better than you would naively think, but still does not decrease the risk of a given condition as much as selecting against that condition directly. 3That is, new mutations in that particular baby, as opposed to older mutations already present in the parents. 4Conflicts of interest: I have used Orchid’s and Herasight’s products on my own embryos (not the ones used to conceive my existing kids, but for a potential third child), employees of Genomic Prediction and Herasight have been extremely helpful in contributing expertise to ACX posts on genetics, and I might invest in this field at some point (though haven’t done so yet). This post started as Herasight asking me to write about their white paper, then spiraled out of control. There were some unexpected time pressures and the result is that I didn’t get a chance to run everything in Herasight’s white paper by their competitors as thoroughly as I would like. Although I talked to representatives of all four companies profiled here, I feel like this probably reflects Herasight’s perspective better than other companies’, and that this is a major flaw. If other companies have responses, I’ll publish them. Thanks to all companies involved for their assistance on this article. Finally, I am favorably disposed toward Herasight because of how I learned about them: a professor named Jonathan Anomaly got cancelled from Penn for being too gung-ho about genetic enhancement, and used his newfound freedom to join a very-early-stage Herasight, raise their ambitions, and sell everyone (including me) on the idea. I grew up on a diet of books and movies about mad scientists, and I’m a sucker for a story about a guy named Doctor Anomaly pursuing revenge against the small-minded fools who destroyed his career by creating a race of superbabies. 5The version of the tool I looked at said 5.9 points for five embryos, up to 9 points for twenty embryos. The version of the tool on their current said says 5.3 - 9, so they might have recalculated after I finalized this article. 6Used in quotation marks because these scores were fine for the predictive tasks they were applied for - they just weren’t finding genes that directly caused the outcome of interest. 7Conflict of interest notice: this table was originally unadjusted. A representative of Herasight claimed that this was unfair, because each company used slightly different reporting conventions, and offered to correct for this in a neutral way. I retraced their reasoning, confirmed that the correction did not especially benefit Herasight at the expense of other companies, and accepted the correction. The original unadjusted table is below: Herasight was insufficiently comfortable with Nucleus’ methodology to even be willing to posit a corrected value, so I left their self-reported value in gray. 8Zagorsky (2007) says an extra IQ point means $234-$616/year in higher salary. The midpoint of $425 equals $670 in today’s dollars; assuming a forty-year career, Nucleus’ +1 point estimate is worth $26,800 (vs. $9,249 Nucleus cost) and Herasight’s +6 point estimate is worth $160,800 (vs. $53,250 Herasight cost). 9As part of researching this article, I asked all four major companies about their within-family validation strategies. Here are some details: Genomic Prediction discusses their strategy in this paper. The results are complicated to interpret - the within-family numbers often have such wide error bars that they overlap with both the across-family numbers and with zero - but looking qualitatively it seems like most scores on average lose about 25% of their risk reduction ability (though averages might not be the right way to do this, and some might be much more affected than others). Their website reports unadjusted, not within-family validated numbers; GP says they say this clearly on their site (which is true), Herasight counters that they still present their numbers as applicable to embryo selection (which is also true). To get the most applicable-to-embryo-selection numbers, you might want to adjust GP’s stated numbers down somewhat; it’s hard to say exactly how much, but maybe 20 - 25%?
Marshall & Swift's Valuation Service

Marshall & Swift's Valuation Service is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 11, 2021 and December 11, 2021. The archive places it in contexts such as "Professionals that value residential and commercial buildings often rely on Marshall & Swift's Valuation Service". It most often appears alongside /r/georgism, ACX community, Aggregate Land Rents, Expenditure on Public Goods, and Optimal City Size.

Mention count
1
Issue count
1
First seen
December 11, 2021
Last seen
December 11, 2021
December 11, 2021 · Original source
...he Cost Approach In this approach, you estimate the cost of the buildings minus depreciation. Professionals that value residential and commercial buildings often rely on Marshall & Swift's Valuation Service . This is a fancy calculator where you plug in all the different characteristics of your building, and it spits out a cost estimate. You can think of it as a Kelley Blue...
...he Cost Approach In this approach, you estimate the cost of the buildings minus depreciation. Professionals that value residential and commercial buildings often rely on Marshall & Swift's Valuation Service . This is a fancy calculator where you plug in all the different characteristics of your building, and it spits out a cost estimate. You can think of...
...imilarly-sized empty lot? That was me (crudely) using the market approach. The Cost Approach In this approach, you estimate the cost of the buildings minus depreciation. Professionals that value residential and commercial buildings often rely on Marshall & Swift's Valuation Service . This is a fancy calculator where you plug in all the different characteristics of your building, and it spits out a cost estimate. You can think of it as a Kelley Blue...
Marvel Unlimited

Marvel Unlimited is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "Marvel Unlimited app". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
Marvel Unlimited
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
When I was growing up the only way to read these old issues was to track down and buy (expensive!) copies from comic book shops and flea markets, or pick up infrequent re-prints. Now all of the old Marvel Comics have been digitized and made available on the Marvel Unlimited app. The app is NOT very friendly to use – especially if you are trying to read the old stuff, but if you are determined (and I was) you can read all of this stuff for $70/year.
MATIC

MATIC is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 28, 2023 and August 28, 2023. The archive places it in contexts such as "It’s all in crypto (using the MATIC token)". It most often appears alongside 2024: Bullish on Blue, ACX forecasting contest, AI Advances by 2025.

Reference entry
MATIC
Mention count
1
Issue count
1
First seen
August 28, 2023
Last seen
August 28, 2023
  • 23 August 28, 2023
August 28, 2023 · Original source
It’s hard to turn that into a prediction market thesis. Will AI win the Mathematics Olympiad in 2024? Maybe math is not the particular thing AI will be good at, or maybe 2024 is too early. Will AI write a best-selling novel? Maybe novel-writing isn’t where AI will shine. Will AI be used in the military? Maybe AI will be great but the military will ban it for political reasons. You’re not sure about any of this. You just think AI is gonna be really big.
If I understand the basic idea, it automatically creates a market for every major flight in the next three days, uses an algorithm to calculate delay chances, and then lets people who think they have extra information (not included in the algorithm) bet the probability up or down. It’s all in crypto (using the MATIC token), so it can probably escape regulatory scrutiny at least for a while.
The picture above shows that the biggest markets have between 3 and 30 MATIC in them, which corresponds to $1.50 - $15 at current prices.
mebendazole

mebendazole is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 28, 2021 and December 28, 2021. The archive places it in contexts such as "albendazole and mebendazole, the current choices for deworming". It most often appears alongside 1DaySooner, 2016 Washington carbon tax ballot initiative, @GoodSciProject.

Reference entry
mebendazole
Mention count
1
Issue count
1
First seen
December 28, 2021
Last seen
December 28, 2021
December 28, 2021 · Original source
The Oxfendazole Development Group, $150,000, to develop oxfendazole. This is a next-generation antiparasitic drug which may one day replace albendazole and mebendazole, the current choices for deworming. Several hundred million children worldwide suffer from parasitic worm infections; this certainly affects their health, and a growing body of research suggests it might affect their cognitive ability, educational attainment, and future income. GiveWell endorses deworming as one of the most effective charitable interventions; the successful development of new antiparasitics would further this effort. Oxfendazole has done well in early studies and this group wants to follow them up in the hopes of eventually getting FDA approval. To learn more or send a donation, see this site
melatonin

melatonin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 28, 2021 and November 28, 2021. The archive places it in contexts such as "it’s pretty similar to melatonin, anti-androgens, and a bunch of other things". It most often appears alongside Abba Eban, ACX, Albert Einstein.

Reference entry
melatonin
Mention count
1
Issue count
1
First seen
November 28, 2021
Last seen
November 28, 2021
November 28, 2021 · Original source
In terms of the more polemical points, I might or might not write a longer response later. Right now the point I think is most important is that Marinos sort of grants that many of the substances with many positive studies probably don’t work - but says ivermectin is different because it has more studies and stronger effects than the others. I think the stronger effects are a bit exaggerated - the graphic that Marinos presents shows it’s pretty similar to melatonin, anti-androgens, and a bunch of other things - but I will grant that it has significantly more studies.
Memory On Hand

Memory On Hand is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Memory On Hand is this simple piece of wearable tech". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Memory On Hand
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#24: Wearable Tech For Improving Memory What if there were a simple piece of wearable tech. that could improve your memory by one item at the push of a button? What would you use it for? The ever-elusive names of people you just met? A friend’s birthday that you always seem to forget? Or perhaps an email address or phone number just long enough to jot it down? A one-item Improvement in memory would be a luxury for a working professional, but can be the difference between independence and dependence for those with objective impairments in memory, such as those affected by stroke or acquired brain injury. Normal declines in memory across the lifespan are also a significant source of anxiety for many healthy older adults, who worry about pathological cognitive decline and dementia. Memory On Hand is this simple piece of wearable tech., and we believe it can help augment memory for any wearer. Unlike currently available memory strategies and solutions like paper note pads or cell phone note taking apps, Memory On Hand can be used without disrupting the flow of the users daily life – and even mid-conversation. Stated simply, we think Memory On Hand can help a lot of people 1) remember more; 2) improve their confidence in their memory abilities; and 3) worry less about memory. We need your help in bringing this innovation to market. More info at www.memoryonhand.org
mepacrine

mepacrine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 24, 2024 and July 24, 2024. The archive places it in contexts such as "the obsolete anti-malaria drug mepacrine has an odd side effect". It most often appears alongside Abigail Shrier, Adragon De Mello, AI girlfriends.

Reference entry
mepacrine
Mention count
1
Issue count
1
First seen
July 24, 2024
Last seen
July 24, 2024
July 24, 2024 · Original source
18: Related: the obsolete anti-malaria drug mepacrine has an odd side effect: it turns your skin yellow. During World War II, some American spies in China would take mepacrine to blend in. And more interesting facts about WWII US spies in China here:
Meta

Meta is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2023 and July 21, 2023. The archive places it in contexts such as "share price of Microsoft/Meta/Apple/etc". It most often appears alongside 2008 Financial Crisis, 2023 book review contest, 30-Year Mortgage.

Reference entry
Meta
Mention count
1
Issue count
1
First seen
July 21, 2023
Last seen
July 21, 2023
July 21, 2023 · Original source
We need a framework for thinking about these trades. Lebron’s first law states that we must know ourselves and our motivations for trading before we trade. We tell ourselves many stories, but someone with intellectual honesty – the person with the most alignment between their motivations and actions – will take money from the person who didn’t go through the work to understand their own motivations. There is a reason that Citadel and other hedge funds pay millions of dollars to trade with retail. They know why they are trading: to maximize profit. And the dilettante who “trades for fun” will be eaten alive by a firm with a much better model of a) the world and b) the dilettante themself. Why did I write this book review? To test my intellectual mettle. I could easily have posted this book review elsewhere, but no, I wanted to see how I stack up against other ACX Book Review contest participants. Similarly, this is often the reason people get into trading. One motivation that Lebron explicitly calls out is intellectual validation. You can toil in obscurity for years as an academic. But in trading, there is a quick feedback loop. If your P&L showed $10M last year and the guy sitting next to you showed $8M, you have demonstrated who is “cleverer” and established a clear hierarchy. What lessons here transfer to our daily lives? Like Paul Graham, Lebron encourages us to keep our identities small. He gives the standard decision-making advice to write down your framework and reasoning for why you made a decision at a specific point in time, in order to avoid biases after the fact. This section of the book contained good general advice, but nothing that will be particularly new for the median ACX reader. 2: Adverse Selection You’re never happy with the amount you traded. Now we start to get into the good stuff. Financial markets are an information aggregation mechanism, relying on multiple parties’ beliefs and recursive Bayesian updates of an individual actor’s beliefs based on the beliefs of others2. Market mechanics demonstrate Bayesian beliefs in action. The following quote is quite long, so skip over it if you don’t want to dive deep into the psychology of making a market. I retained it in full because this is quite literally the best description I’ve ever seen of the Bayesian dance between two market makers: “You are a market maker in South African mining companies. Through years of effort and continual improvement, you have built a trading model for the company Veldt Resources. You walk into work one day, ready to set up your trading for the day. It's a stock that doesn't trade much, and usually there are only two market makers: you and another (we'll call her Jo). She's sharp, and she competes well to trade against customer orders that come in. Your model has Veldt valued at 54.35 ZAR (South African rand). You're going to start quoting the stock, so you're about to turn on your machine making a market 54.25 - 54.45 (1000x)3. Before you turn on, you check the current market and notice that Jo has already turned on and she's making her market 53.50 - 54.00 (2000x). If you were to turn on your machine, your market would cross her market, and you would buy 1000 shares from her for 54.00. You now need to make a decision. Whose model do you believe more, yours or Jo's? If you believe yours, you should turn on your machine, trade at 54.00, and expect to make money. If you believe Jo's model, you should adjust your own model parameters to match her market and turn on, making a similar market to hers. What to do? As with many dichotomies, this is a false one. And as with many decision processes, Bayesian reasoning lights the way… …Jo presumably believes Veldt is worth around 53.75 (the average of her bid and offer). But how confident is she in her belief? The width of her market can give you a clue. It's 0.50 ZAR, whereas yours was going to be 0.20 ZAR wide. All other things equal, you should think that Jo only has 40% (0.20/0.50) of the confidence in her fair value as you do in yours. On some absolute scale of confidence, you can say you had a belief-strength of 100 in your fair value of 54.35 (before seeing Jo's market), and Jo has a belief-strength of 40 in her fair value of 53.75 (before seeing yours). And it turns out the weighted average of these two beliefs is quite a reasonable way to combine them: 100/140 * 54.35 + 40/140 * 53.75 = 54.18. Your updated fair value, having seen Jo's market, is thus 54.18 ZAR. This procedure is a quick, heuristic, and reduced version of Bayesian belief-updating, and a good reference on the subject is A.L. Barker's 1995 paper. After updating, you now believe that the stock is worth 54.18. Assuming your trading costs, risk limits, and return requirements are satisfied, buying 1000 shares for 54.00 is a good trade. Naively, you might just put out a 54.00 bid for 1000 shares, trade with half the 2000 share offer, and hope to collect your expected-value ZAR. In practice, however, you might be able to make even more. If Jo is making a 0.50 wide market, maybe she'd be willing to sell lower than 54.00. It's conceivable that if you put out a 53.90 bid for 1000 shares, Jo will sell at that price, and you collect an extra 100 ZAR! Of course, Jo could react differently. She could see your bid and use that information to change her market, in much the same way you did before turning on. These are difficult decisions, ones where experience with the product and the market make a big difference in being able to eke out a little extra edge. Let's play it safe however and pay 54.00 for 1000 shares. You trade, and Jo reacts by immediately canceling her market. This is not an uncommon occurrence in illiquid stocks, especially in emerging markets, so you're not too surprised. You wait a couple of minutes, mentally visualizing Jo in front of her six monitors, evaluating her trade and her model. Finally, she turns back on. Her new market is 53.50 - 54.05 (10000x)! You reason that Jo has seen that someone (you) disagrees with her valuation of the stock. Jo is a good Bayesian like you, and so she has incorporated that information into her model and updated her beliefs about the fair value of the stock. Her updated belief is that she now wants to sell even more stock, at a marginally higher price. Clearly, she almost entirely discounts the information you've communicated to her with your trade. How should you react? It seems fairly clear that, assuming Jo is not a crazy or incompetent market maker (usually a fair assumption), your trade was a bad one. You bought 1000 shares, when in retrospect, you would have wanted to buy much less, probably zero. Imagine instead that Jo had turned back on with a market of 54.00 - 54.50 (1000x). Her reaction now clearly indicates the information you gave her with your trade is valuable, and she has adjusted her beliefs accordingly. Your trade was probably a good one. Don't you wish you had bought all 2000 shares on offer? No matter what Jo's reaction is, you will be unhappy with your trade. Note that Jo will be unhappy too, since retrospectively she should have either made her initial market bigger or smaller. Welcome to the joyous world of trading!” Whether or not you make money, you have regrets! If you profited, you could have made more. If you lost money, you shouldn’t have made the trade at all. Like death and taxes, you can’t avoid adverse selection. Lebron continues to highlight a few areas of trading that have adverse selection problems. First, IPOs. If you buy the stock in an IPO, you expect the share price to “pop” on the first day of trading. However, if others also have this expectation, the round will be oversubscribed. You can only get the quantity of shares that you bid for when the market doesn’t think the shares will go up. So if you are able to get the shares that you want, the IPO is likely a dud. See also: Venture Capital fundraising. Second, powerful entities that change the rules of the game while you’re playing. Exchanges nullify “erroneous” trades. Brokerages limit buying. Anyone who tried to buy GameStop stock on Robinhood on January 28, 2021, knows this form of adverse selection all too well. Lebron also highlights “special trades”, in which you should throw the “normal rules” out of the window. This advice generalizes to other areas of life: “The normal rules do not apply. If you remove yourself from our usual routine, if you think hard and clearly about the specific situation, maybe you can do something good. Perhaps even great. Others will be paralyzed by inaction, but perhaps you won’t be. Crises can be opportunities.” 3: Risk Take only the risks you’re being paid to take. Hedge the others. In trading, as in life, you can make the right call in expected value terms but still lose due to randomness. Some of that randomness is avoidable. Some of it is not — and can be accounted for by hedging. Here, Lebron encourages us to rely on multiple risk measures and actively seek to understand the risks that we might be subject to. That’s all well and good in the world of finance, with derivatives contracts. But how might this apply in other areas of life? If you work for a publicly traded company and are compensated in stock, sell your shares as soon as you receive them. This is not because I don’t expect the share price of Microsoft/Meta/Apple/etc. to go up. The stock may very well outperform the market. But you are not being compensated for the added risk that you take on here. Your employment prospects at Microsoft/Meta/Apple/etc. are highly correlated with the share price. When the share price is down is when layoffs happen. Former Enron employees can chime in here. Similarly, it makes sense to hedge anything that is outside of your control. Let’s say you’ve decided the crypto bear market of 2023 is a great time to start a new crypto company. Your success depends on things within your control, such as: Your idea
Metamucil

Metamucil is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "I have been pounding Metamucil". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Metamucil
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
metformin

metformin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "I'm late commenting but I don't see anyone mentioning metformin yet"; "Metformin has many good qualities and is inexpensive"; "my daughter was pre-diabetic and had been put on Metformin and Ozempic". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
metformin
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I'm late commenting but I don't see anyone mentioning metformin yet.
Metformin is off-patent and although its only on-label use is for diabetes, some people think it extends life expectancy. (The main evidence for this is that diabetics who take metformin live longer on average than people who aren't diabetic.)
Surely people who are thinking about taking semaglutide should try metformin first?
methadone

methadone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2022 and June 23, 2022. The archive places it in contexts such as "three-quarters receiving an opioid substitute like methadone or Suboxone". It most often appears alongside 1978, 2016 essay, A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs.

Reference entry
methadone
Mention count
1
Issue count
1
First seen
June 23, 2022
Last seen
June 23, 2022
June 23, 2022 · Original source
Results of a survey at one of SF’s new Navigation Centers at why their clients refused to go to normal shelters. But even the homeless people who do want to go to shelters mostly can’t get in. This app gives the current status of San Francisco’s homeless shelter waitlist. If you applied today, there would be 900 people ahead of you in line for one of the city’s 1500 - 2500 shelter beds. The app says that the median wait time is 826 days. So however many homeless people don’t want to go to shelters, we’re not building enough shelters to serve the ones who do. Why not? Shellenberger again: In the spring of 2021, Friedenbach published an op-ed opposing a proposal considered by the San Francisco Board of Supervisors to create, within eighteen months, sufficient homeless shelters and outdoor “Safe Sleeping Sites” for all of the city’s unsheltered homeless. “One can simply take a look to New York City,” she wrote. “Their department spends about $1.3 billion dollars of its budget on providing shelter for their unhoused population while thousands remain on the street. . . . As a result, New York has a higher rate of homelessness than San Francisco.” Housing First advocate Margot Kushel of the University of California, San Francisco agreed. “The problem with New York—and I spend a lot of time with people working in the system in New York—is that they spend an estimated $30,000 for each person per year to keep them in shelter. That’s not what we want to do. Because if you create the shelter and you don’t create the housing, then people are just in shelter forever.” Housing First advocates oppose shelter in Los Angeles. “Why haven’t we solved homelessness?” asked Housing First creator Sam Tsemberis. “Because [Los Angeles mayor] Eric Garcetti [has] Andy Bales [saying,] ‘You need emergency housing.’ ‘These people need to be cleaned up.’ ‘They need to be sober.’ ‘They need Jesus before they’ll be ready for housing.’ I said, ‘People should be housed and then maybe they’ll get sobriety and Jesus and the rest.’ We’re definitely on polar opposites of the whole thing.” Advocates for the homeless at the national level similarly oppose more shelters. “I don’t agree that we should be building more transitional housing,” said the head of the National Alliance to End Homelessness. […] In other words, the reason that there are so many homeless people on the streets in San Francisco is that both progressive and moderate Democratic elected officials, and the city’s most influential homelessness experts and advocates, have for two decades opposed building sufficient shelters. And that is unlikely to change even after San Francisco starts spending hundreds of millions more per year on the problem and might even get worse. This basically seems true. I found this webpage of a former SF Supervisor candidate a helpful corroborating source. He was running on a platform of “maybe we should build some homeless shelters”. He lost. You can also find a bunch of webpages by the sorts of people Shellenberger is complaining about, for example this site: Sup[ervisor] Rafael Mandelman today pushed his new legislation that would require the city to offer at least temporary shelter to everyone living on the streets, a step that some say would lead to more homeless sweeps and do nothing to create permanently affordable housing . . . [our] Coalition has argued for years that the solution to homelessness is housing—not temporary shelter, which may never lead to housing. The ex-supervisor candidate gives some helpful numbers: permanent housing costs about $600,000 per person housed. Shelters cost between $20,000 and $30,000 per person housed. So SF could build enough shelters to clear its waitlist for about $30 million. More recently, SF has tried a sort of compromise, opening “deluxe” shelters called Navigation Centers which avoid some of the problems of regular shelters. They also cost more than twice as much, and the city has only created about 300 beds. Also, the people in regular shelters are angry, because being in a regular shelter disqualifies you from getting into a (much better) Navigation Center. Some of them are considering leaving their shelter, going back on the streets, then waiting however many months or years it takes to get a Navigation Center bed instead. I’m not at all sure of these numbers, but it looks like of SF’s ~7,000 homeless, about 2,000 are in shelters already, and 1,000 are on the shelter waitlist. I don’t know if the remaining 4,000 have made a specific commitment not to go to shelters, or just have given up on the waitlist process. My conclusion: agree with San Fransicko about the role of progressive activists, but I think it overemphasizes the role of wanting to use drugs in why homeless people themselves sometimes avoid shelters, and underemphasizes the many other problems with them. Claim 5: Drug Decriminalization Isn’t Working California legalized marijuana in 2016. Shellenberger says that San Francisco’s commitment to drugs has gone beyond that: it has effectively decriminalized opioids, cocaine, and the rest. Any attempt to lessen use of these drugs is attacked as “stigmatizing”; instead, government policy centers around providing addicts with needles and other drug paraphernalia under the guise of “harm reduction”. Shellenberger hits all the right beats here. Like many people, he tries to undo the damage done by The New Jim Crow, a book which convinced millions of people that mass incarceration was driven by a racist War On Drugs. In fact, less than a fifth of prisoners are in for drug-related crimes. And when the government was first debating the War on Drugs and mass incarceration, black leaders were among the strongest proponents of both. The talking point at the time - among everyone from black Congressional leaders to black churches - was that the government’s failure to crack down on drug use was racist, borne of them not caring about predominantly black drug victims. And while we’ve been patting ourselves on the back about how enlightened we are for ending the drug war: Drug overdoses are today the number one cause of accidental death in the United States as a result of America’s historic addiction and overdose epidemic. Overdose deaths rose from 17,415 in 2000 to 93,330 in 2020, a 536 percent increase.Significantly more people die of drug overdoses today than of homicide (13,927 in 2019) or car accidents (36,096 in 2019). […] There are about twenty-five thousand injection drug users in San Francisco, a number 50 percent larger than the number of students enrolled in the city’s fifteen public high schools. San Francisco gives away more needles to drug users, six million per year, than New York City, despite having one-tenth the population. The part of this chapter that stood out to me as most worth looking into deeper was the section on Portugal: For decades, harm reduction and decriminalization advocates have pointed to Portugal as a model, noting that it decriminalized drugs and expanded drug treatment. In 2013, Portugal’s drug-induced death rate was sixty-six times less than that of the United States. The number of people in treatment increased by 60 percent between 1998 and 2011, with three-quarters receiving an opioid substitute like methadone or Suboxone, the brand name of buprenorphine. Drug use among 15- to 24-year-olds actually declined after decriminalization. “All drugs have been legalized,” explained Monique Tula, executive director of the Harm Reduction Coalition. “Their focus is on giving people tools, like job apprenticeships, and the means to support themselves.” […] [But Portugal] never legalized drugs. It only decriminalized them, reducing criminal penalties but maintaining prohibition. Drug dealers were still sent to prison even after the 2001 decriminalization. And Portugal does not let people addicted to hard drugs with behavioral disorders off the hook like progressive West Coast cities have done. It’s true that Portugal massively expanded drug treatment, but people are still arrested and fined for possession of heroin, meth, and other hard drugs. And drug users are typically sent to a regionally administered “Commissions for the Dissuasion of Drug Addiction,” composed of a social worker, lawyer, and doctor who encourage, push, and coerce drug treatment. And decriminalization doesn’t end drug violence. “Even if trafficking enforcement decreased, like it did in Portugal,” said criminologist John Pfaff, “illegal drug markets would still be forced to rely on violence to resolve disputes.” Indeed, prostitution and violence are ever-present in the open-air drug scenes in San Francisco, Los Angeles, and Seattle. “We are seeing behaviors from our guests that I’ve never seen in thirty-three years,” said Rev. Andy Bales, who runs the largest homeless shelter on Skid Row in Los Angeles. “They are so bizarre and different that I don’t even feel right describing the behaviors. It’s extreme violence of an extreme sexual nature.” People are not dying from drug overdose deaths in San Francisco because they’re being arrested. They’re dying because they aren’t being arrested. Decriminalization reduces prices by lowering production and distribution costs, which increases use. This was also the case for alcohol consumption. It increased after prohibition ended in the United States. Even in Portugal, drug overdose deaths and overall drug use rose after decriminalization. I was most surprised by the claim that Portuguese overdose deaths rose after decriminalization. Uncharacteristically, San Fransicko doesn’t give a citation for it, but we can try to retrace its reasoning. Decriminalization proponents tend to point to these numbers, helpfully converted to per 100,000 population and graphed here: But an anti-drug Australian think tank argues that the peak in 2001 is made up: Claims that there were more than 75 drug-related deaths in 2001 which more than halved to 34 deaths in 2002 use a figure for 2001 for which there is no substantiation. Official drug-related deaths for Portugal, taken from the latest 2018 EMCDDA Statistical Bulletin are copied below. Notice that there is no such figure recorded for 2001. They include a link to EMCDDA, the EU organization charged with monitoring these things. The link contains two datasets, both of which seem to be measuring the same thing but getting different results. One dataset starts in 2002, the other in 2008. I don’t know what the difference here is, but they’re right that neither includes 2001. If you ignore the pre-2002 data, the graph looks like this: They say “opiate”, but AFAICT these numbers are actually about all drugs. But the proponents link to the updated 2020 version of the same website, which all of a sudden does have data from 2001 and before. I don’t know why EMCDDA can’t make up its mind, but I think the Australians are wrong and the original graph is fine. On the other hand, does it really matter? Both of these show drug deaths decreasing until 2005, then going up and down a bit, then going back up again starting in 2011. I think a reasonable interpretation would be that decriminalization in Portugal did decrease overdose deaths a bit, and then they started rising again from that low baseline around the same time other European countries saw rising overdose deaths. I would also accept “these are pretty small effects and we shouldn’t ascribe any significance to them”. But San Fransicko’s claim - that overdose deaths increased after the reform - seems false. The only way I can see justifying it is taking the second graph - the one that wrongly claims there is no pre-2002 data - and then attributing the fact that twelve years after the reform lowered deaths, deaths finally rose above the pre-reform level to be the fault of the reform. This is like saying “people claim the Black Plague killed a lot of Europeans, but the European population actually rose after the Plague”, which is true in the sense that it was above its pre-Plague max by like 1600 or whatever. What about overall drug use? Here I recommend A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs, which is on exactly this topic of how people keep selectively quoting results from Portugal to prove their point. It argues that drug use is inherently hard to measure. There are four different Portuguese datasets for the time at issue, lots of different drugs, lots of different age/gender combinations, and lots of different ways of measuring drugs (did you use drugs in the past month? the past year? your lifetime?) It’s easy to tell a story of how past-month cocaine use skyrocketed among 14-29 year old males according to X source, or how lifetime marijuana use fell in high school-age women according to Y. The main trick that opponents use is measuring lifetime drug use. Portugal is a very conservative country; drug use is pretty new and most of the older generation wasn’t involved. So as time goes on and more and more people try drugs but “un-trying” drugs isn’t a thing, the percent of the population who have tried drugs inevitably goes up. This definitely happened but isn’t a fair reflection of any specific reform. The authors find that in the past decade or so, there has been a bit more short-term experimentation with drugs, but less long-run use. They conclude: As shown in Figure 2, general population (aged 15–64) trends for recent and current drug use in Portugal indicate minimal if any changes between 2001 and 2007. Instead, rates of discontinuation of drug use (the proportion of the population that reported ever having used a drug but opting not to in recent years) increased, which reinforces that just as in the school populations, the growth in lifetime-reported use reflected predominantly short-term experimental use. Increases in recent and current drug use were more notable in some cohorts, particularly those aged 25 to 34 (albeit, with a maximum of 7% of any one cohort reporting recent use, absolute levels remained low). But as shown in Figure 3, recent and current drug use declined among those aged 15–24, the population who were most at risk of initiation and long-term engagement. The available evidence thus gives grounds for arguing that while there was some growth in the scale of drug use in post-reform Portugal, there was an overall positive net benefit for the Portuguese community. What about San Fransicko’s main point - that as the US has wound down the War on Drugs, drug overdose rates have sextupled? I think this is mostly not causal. I think the sextupling of overdoses is a combination of expansion in prescription opioid use, various forms of social decay making people less happy and therefore more likely to use drugs, and “improvements” in drug “technology” and the “supply chain” (eg production of fentanyl in China). I don’t know of any source that attempts to tease out the exact contribution of all of these things, but I would note that overdose deaths have risen the most in very conservative Midwestern states that haven’t walked back the drug war as much as California. Conclusion: As usual, I appreciate San Fransicko’s corrections to the prevailing narrative, but its own additions are dubious. Its claim that Portugal saw increased drug-related deaths seems false as far as I can tell. Its claim that it saw increased drug use depends on your definition, but is misleading and not the most natural way to sum up the evidence. Claim 6: San Francisco’s Soft-On-Crime Policies Led To Rising Crime Ten years ago, the news was full of stories about how some teenager stole a gumdrop and was sentenced to nine hundred billion years in jail. At some point, there was a genre shift to stories about how some hardened criminal murdered fifty people with an axe and the judge let him go with a warning because having jails felt racist. Source: Ed West, do note that this example is from the UK How suspicious should we be of each type of story? There will always be an extreme right tail of overly harsh sentences, and an extreme left tail of overly lenient ones. Were the 2000s really as draconian as they felt? Is the modern era really as pathetic? Or is it all just a function of who you read and what agenda they’re pushing? Shellenberger: During California governor Jerry Brown’s time in office, voters passed several reforms aimed at reducing the size of the prison population. In 2012, voters passed a change to the Three Strikes law so that the third strike imposes a life sentence only if the new felony was serious or violent. In addition to lowering punishments for drug possession, Proposition 47, which voters passed in 2014, redefined shoplifting, forgery, petty theft, and receiving stolen property as misdemeanors when the value in question does not exceed $950. In 2016, voters approved a proposition that shortened the time it took for some nonviolent offenders to be eligible for parole and which released nonviolent offenders into drug treatment and rehabilitation. Property crimes rose in San Francisco starting in 2012. Larceny, which is shoplifting and other petty theft, rose 50 percent, from roughly 3,000 incidents per 100,000 people in 2011 to about 4,500 in 2019. Property crimes as a whole, which include larceny, motor vehicle theft, and burglary, rose from 4,000 incidents per 100,000 people in 2011 to 5,500 in 2019. One study suggests that Proposition 47 increased the rate of auto theft 17 percent and the rate of larceny (non-auto property) theft 9 percent, but discerning between causation and correlation may not be possible. Upon taking office in January 2020, [famously soft-on-crime San Francisco district attorney Chesa] Boudin followed through on his campaign promises. Instead of prosecuting and incarcerating people for breaking car windows to steal money and other items from inside, Boudin proposed creating a $1.5 million fund to reimburse car owners. But there were over 25,000 car break-ins reported in 2019. If every break-in cost just $250 in repairs, the fund would need four times that amount. And what would prevent people from falsely claiming to have been robbed in order to get city money? […] Boudin opposed efforts by the mayor and the city attorney to prevent drug dealers who had already been arrested from entering the Tenderloin. “Until the city is serious about treating addiction and the root causes of drug use and selling,” said Boudin in a statement, “these recycled, punishment-focused approaches are unlikely to succeed at doing anything more than making headlines.” Home burglaries rose in early 2021 in San Francisco. Homeowners started posting on Twitter videos from their security cameras of people breaking into homes and garages. “When I first moved here we had a car break-in problem,” said Michael Solana, a writer who works for a venture capital fund. “Now we have a home invasion problem. These things are wearing on people.” Boudin attributed the rise of burglaries in San Francisco to the decline of tourism and “people in desperate economic circumstances.” Progressive supervisor Hillary Ronen agreed. “We know that [economic insecurity and inequality] is one of the root causes of property crimes specifically,” she said. But Tom Wolf and others argued that the robberies were, like the shoplifting, done by people seeking money to buy drugs and feed their addictions. “The drugstores have been shoplifted to death and that’s all because of drug use,” said Tom. “I know. I used to do the same thing when I was out there. That’s what you do. You ‘boost.’ And then you go and you sell your stuff down at UN Plaza,” an open-air drug scene. In a May 2021 city supervisors’ meeting, a representative from CVS called San Francisco “the epicenter of organized retail crime in the country” and claimed that 85 percent of the shoplifting is committed by organized theft rings. Police broke up one such ring in October 2020 and recovered $8 million of stolen merchandise. The problem goes beyond property crime. Boudin declined to prosecute two men who went on to kill people. One man had been repeatedly arrested for stealing cars, despite having just been released from prison earlier in the year, and appeared to be abusing meth. On New Year’s Eve, 2020, the man killed two people while driving intoxicated. Police found inside of his car a semiautomatic handgun and twenty-three grams of methamphetamine. On February 4, another intoxicated driver killed a pedestrian in a stolen car. The San Francisco police had arrested him in October 2020 for possessing a stolen car, a tool for stealing cars, and what appeared to be meth. Boudin chose not to pursue charges. In December, the California Highway Patrol arrested the man again for driving a stolen vehicle under the influence. Again he was not prosecuted. The accident victim, an immigrant from Kenya, and his wife had moved to San Francisco two weeks before the fatal crash. “I blame the DA,” said the widow of the victim. The suspect, she said, “was someone who was out in the public who shouldn’t have been in the public. It was completely avoidable.” Tom said he could feel the difference on the streets. “Drug dealing is unabated and it’s not one guy, it’s fifty guys dealing fentanyl and meth,” he said. “And it’s going unabated because the district attorney says, ‘These are the nonviolent, quality-of-life crimes,’ and ‘I’m not going to prosecute them.’” [..] District Attorney Boudin was offering weaker sentences than even defense attorneys were requesting, according to Vicki Westbrook of San Francisco. “There’s a defense attorney who said, ‘It used to be that I would argue for this deal in court with the DA but now I don’t say anything because the DA is going to offer me a deal better than what I would have suggested. Somebody shot up the street with an automatic weapon. The first offer was six months in jail or time served plus two years of probation or something. And then [the DA] said, “How about thirty days in jail?”’” Vicki laughed. “You really can do anything in San Francisco,” she said. “If you do get arrested, chances are you’re going to be out of jail in less than thirty days for damn near everything except maybe killing somebody and maybe even then, too. It’s hard to say at this point.” Taking each of these points individually: Proposition 47 There are two good big studies on the effects of Prop 47, one by Public Policy Institute and one by some UCI criminologists. The PPI study finds that the proposition increased theft and car break-ins by about 10%. The UCI study finds the same, but notes that under different assumptions the effects wouldn’t quite obtain statistical significance. This seems a bit too much like post hoc trying to get rid of an inconvenient effect, plus an effect on the border of statistical significance is different from positively finding no effect. I think a reasonable interpretation is that theft and car break-ins rose about 10% because of the proposition, just as Shellenberger says. Some pro-47 sites note that most states have some limit on how much you to have to shoplift before it’s a felony, and Prop 47 brought California closer to the national average, rather than turning it into an outlier. Chesa Boudin Chesa Boudin took office two months before the COVID pandemic began. Any attempt to separate the effect of Chesa Boudin from the effect of the pandemic is doomed. Shoplifting definitely plummeted when Boudin took office, but that’s because all the stores were closed. Murders definitely rose a little after Boudin took office, but that’s because that was also when the Black Lives Matter protests happened, which demoralized police and led to a so-far-permanent spike in murders nationwide. Percent of criminals caught definitely fell when Boudin took office, but that’s because various aspects of the justice system were closed for COVID (I will grudgingly entertain speculation that a further decrease in arrest rates from 2020 to 2021 may have been a genuine Boudin effect). In the absence of any real way to judge his performance, I think San Fransicko’s points about Boudin are plausible, though speculative. Shoplifting This one is terrible. There’s a surprisingly spirited debate here (some of you may have already read Applied Divinity Studies’ article). The debate is: everyone on the ground in San Francisco - store owners, security guards, customers, random citizens - say that shoplifting has increased massively over the past decade. But statistics mostly say it hasn’t. Source here. This is shoplifting crimes per 100,000 people. Kern County is a deep red county in California (including Bakersfield) that is known for being tough on crime. Against this, seriously, everyone says that shoplifting has obviously increased. I had a patient who worked in shoplifting prevention, he told me - his psychiatrist! Who he had no reason to lie to! - that he was constantly stressed dealing with the shoplifting surge devastating the stores he covered. Here’s the San Francisco subreddit’s response to someone posting the data showing shoplifting hasn’t risen - it’s just a lot of people laughing hysterically. What’s going on? I was able to find a different set of statistics that does seem to show a longer-term increase in shoplifting (source): The very big spike at the end might be a change in reporting by one or two stores - you can find the argument here. But it does look like shoplifting went from about 125 incidents/month in the early 2010s to more like 250/month just before the pandemic. Why is this graph so different from the other one? It looks like the top one came from the Department of Justice, and the bottom one came from SFPD. I’m not sure why these report differently. When you multiply out by 800K people in SF, by 12 months/year, and 30ish days/month, the first graph corresponds to 4 shoplifting incidents per day, and the second to 6. As LouB’s analysis here points out, that seems suspiciously low for a city of 800,000 people where stores are constantly closing because of shoplifting. Maybe off by a factor of a few hundred from what we’d expect. LouB writes: The SFPD report only references shoplifting offenses that required SFPD officers to prepare an incident report. That means either the shoplifter fought security, committed additional crimes, or stole more than $950 worth of items. It’s not that SFPD’s report is erroneous, it’s just not a representative statistic. In a parallel statistic, SFPD only completes incident reports for traffic accidents when there is an injury. Therefore, thousands of noninjury accidents are handled civilly without SFPD reports the same way thousands of shoplifting offenses are handled without reports. An insurance company would not determine premium rates based solely on SFPD incident reports, nor should readers interpret SFPD shoplifting reports as anywhere near the total picture of the shoplifting epidemic in San Francisco. (this would also explain why one or two stores changing their reporting policy can produce a spike equal to everyone else in San Francisco combined) But comparing incident reports from 2010 to incident reports from 2020 should still be apples-to-apples, unless the likelihood of reporting any given incident changed in the meantime. Did it? This news article quotes a San Franciscan who says that when they try to report shoplifting incidents, the cops tell them not to because “it doesn’t make a difference”. If cops say that now more often than they used to, it would make all these statistics meaningless. (Applied Divinity Studies claims to have an argument that shows this can’t be true. It goes something like: if San Francisco was a better place to shoplift than its neighbors - eg Oakland - then shoplifters would leave Oakland to go to San Francisco, and we would see Oakland shoplifting rates falling. Oakland shoplifting rates are falling, but no more so than the rest of the state, so there can’t be increased tolerance for shoplifting in San Francisco. I find this dubious for many reasons. First of all, many of the same reasons shoplifting is up in San Francisco - like Prop 47 or soft-on-crime progressive policies - also apply to Oakland. Second, given that shoplifting fell massively everywhere because of the pandemic, it feels dubious to try to compare different cities; maybe one city had stricter pandemic lockdowns than others. Third, do criminals really shop around for friendly jurisdictions? If so, why are so many crimes like car break-ins, concentrated in “the bad part of town”? Why wouldn’t criminals leave the bad part of town for under-exploited areas with richer residents and less competition? Maybe criminals in fact aren’t very strategic or mobile? Maybe they don’t want to stand in the BART station and then take a half-hour train ride holding a bag of stolen goods?) Maybe a better argument against this being true is how stable the shoplifting rates have been over time. Wouldn’t it be weird if (let’s say) a tripling of the real shoplifting rates was matched by a third-ing of the reporting rates (rather than a halving or a quartering or whatever)? On the other hand, here’s Shellenberger with some helpful data: Some of this is probably because of Proposition 47, which made some forms of shoplifting punishable with citation rather than arrest (but wouldn’t that be a clear discontinuity rather than a gradual trend?) But overall it sure seems like shoplifting is being taken less seriously, which might encourage people to report less. Another statistic I see is that only 2.3% of shoplifting cases result in an arrest; I don’t know how this is different from the graph above with numbers in the 30s; maybe it involves different levels of what makes something a “case”. I accept that the data don’t consistently show a spike in shoplifting. But what’s the alternative? My patient who works in loss prevention in SF stores is lying to me? The nice elderly Chinese man who sold me my last pair of glasses and chatted to me about the rampant shoplifting in his mall was lying? The San Francisco police are lying? Walgreens pretends to be concerned about shoplifting as part of a dastardly plot to close a bunch of stores for no reason? Target and CVS pretend to care about shoplifting as part of a plot to restrict their stores’ opening hours for no reason? Every big store near me has suddenly gotten a security guard at the front as part of some corporate-sponsored jobs program? Maybe the conservative narrative that soft-on-crime San Francisco must be experiencing rising crime rates took on a life of its own. Maybe it infiltrated not just the usual suspects like the SF police unions, but even such supposedly-liberal bastions as the New York Times. Maybe lots of big corporations took advantage of the fake narrative to make unpopular business decisions they were planning on making anyway. And maybe ordinary San Franciscans, confronted with everyone telling them they were in a shoplifting epidemic, started paying more attention to security guards and petty criminals who had always been there, a sort of mass hallucination that gripped everyone in the city. I can’t rule this out. Americans thought crime was rising all throughout the early 2000s, when it was in fact way down. Or maybe some statistics that we already know are off by several orders of magnitude got off by an additional factor of two or so. I think this one is more likely, but I’m genuinely not sure. Other Crime From the Economist: The Center on Juvenile And Criminal Justice puts it even more starkly, arguing that “San Francisco’s ‘Crime Wave’ Is Just One Crime”: This are potentially susceptible to the same reporting bias as shoplifting. So what about homicide? Homicide is practically always reported and investigated, making it a gold standard in crime measurement. (source) Looks pretty good until 2019. I don’t expect to gain useful information post-2020; the pandemic and the post-George-Floyd murder surge will make it impossible to evaluate for local variation. What about compared to other places? For some reason this top 20 table fails to list Washington DC, which should be just before Atlanta. SF doesn’t make the top 20, although its neighbor Oakland does. Probably most murder variation in US cities is explained by percent African-American and maybe percent Borderer; with relatively few people in these groups SF was never in the running. I’m not sure if some abstracted version of the city with all demographic factors adjusted away would have an unusually high murder rate, but at that point it would be pretty distant from any interesting real-world question. You can see the leaderboard for other types of crime here; San Francisco is often in the top ten, but never the top three. As far as I can tell, San Francisco has seen a big spike in car breakins over the past few years, with no clear trend for other property crime, violent crime, or homicides. It’s not an outlier among American cities in any kind of crime. Conclusion of this section: San Fransicko’s specific claims are basically correct, but suggest a medium-term rise in SF crime which is mostly contradicted by the data. These show stable-to-decreasing murder, stable-to-decreasing violent and property crimes other than car break-ins, and large rises in car break-ins only. The data also show stable-to-decreasing shoplifting, but I’m not sure how much to trust them vs. common sense. Honestly, I’m pretty confused here and not sure what to think. Claim 7: Jim Jones (Of Kool-Aid Cult Fame) Used To Be The Chairman Of SF’s Housing Authority Okay, this isn’t really a statistical claim that I can research different perspectives on. Still, it’s so wacky that I couldn’t resist mentioning it in this review. Jim Jones, famous for killing everyone in his Guyana-based Jonestown cult with poisoned Kool-Aid, used to be the SF government’s top guy on homelessness. Shellenberger writes: Jones married and moved first to Northern California and then to San Francisco with his wife to start a church. He called it the People’s Temple. Jones believed he was the leader of a socialist revolution. He warned of nuclear war and claimed black people would be put in concentration camps. He became a hugely charismatic preacher among African Americans, the disaffiliated poor, and young transplants to the city looking for community. Scenes from the era show a remarkably large and diverse congregation smiling and singing. The People’s Temple grew and provided services. Jones cultivated two progressive San Francisco politicians, George Moscone and Willie Brown, and mobilized people to volunteer for their campaigns […] His son and a San Francisco historian believe he stole the mayoral election for Moscone in 1975. Historian David Talbot, founder of the progressive website Salon, points to evidence that Jones committed sufficient voter fraud to account for Moscone’s narrow 4,443-vote margin of victory. “We loaded up all thirteen of our buses with maybe seventy people on each bus, and we had those buses rolling nonstop up and down the coast into San Francisco the day before the election,” said Jones Jr. “Could we have been the force that tipped the election to Moscone? Absolutely! Slam dunk. He only won by four thousand votes.” When federal investigators looked into fraud claims three years later, they discovered that all of the records were missing from the city of San Francisco’s registrar of voters. Jones also boasted of providing Moscone with black women from his congregation for sex. One time Moscone, drunk and “accompanied by a young black woman whom the politician had kindly agreed to drive home,” crashed into another car. Another time, Moscone and Willie Brown “were with a black woman in an alley at two in the morning at some restaurant in North Beach,” said a local bar owner. State legislator “John Burton was part of that gang too. They were all using marijuana and cocaine.” Said Jones Jr., Moscone would “always be there at temple parties with a cocktail in his hand and doing some ass grabbing.” A Temple member overheard Jones speaking to Moscone the day after one of those parties saying, “I want to let you know that the young lady you went off with is underage,” adding, “Now don’t worry, Mayor, we’ll take care of you—because we know that you’ll take care of us.” Afterward, Moscone made Jones the chairman of the powerful San Francisco Housing Commission. Jones cultivated progressives with money and favors. He made large donations to the ACLU, the NAACP, and United Farm Workers. Jones and Moscone met privately with vice presidential candidate Walter Mondale on a campaign plane a few days before the 1976 presidential election, and Mondale praised People’s Temple shortly afterward. Jones met with First Lady Rosalynn Carter several times. Governor Jerry Brown praised Jones. Glide Memorial Church’s Rev. Cecil Williams loved Jones. There is a photo from 1977 of a smiling Williams awarding Jones the church’s “Martin Luther King, Jr. Award.” Jones used his perch as chairman of the Housing Commission to fight for housing for the poor. He tried to use eminent domain to acquire the International Hotel, a single resident occupancy hotel. After a court sided with the hotel’s owner, Jones mobilized seven thousand protesters to picket it. By mid-January 1977, the situation had become heated. There were rumors that protesters inside the building were armed with guns and Molotov cocktails. Jones lost the legal battle in 1977, and the tenants were evicted. But the drama was a publicity victory for Jones, which burnished his image as a white savior. A conservative member of the Board of Supervisors who was defeated in the mayoral election by Moscone accused the new mayor, the San Francisco Chronicle, and the rest of the city establishment of being blind to Jones’s extremism. “There’s no radical plot in San Francisco,” insisted Moscone, in response. “There’s no one I’ve appointed to any city position whom I regard as radical or extremist.” Willie Brown, a powerful state legislator from 1964 to 1995 before becoming mayor in 1996, “seemed oblivious to Jones’ hucksterism and demagoguery,” notes a historian. Brown was master of ceremonies at a dinner for Jones in the fall of 1976 attended by an adulatory crowd of the rich and powerful, including Governor Jerry Brown. “Let me present to you a combination of Martin King, Angela Davis, Albert Einstein . . . Chairman Mao,” he said, to loud applause. And yet Jones was contemptuous of Brown even as Brown did Jones more and more favors. Jones mocked Brown for his designer suits, sports cars, and women. Once, while Brown was addressing the congregation and Jones was seated onstage behind him, Jones flipped his middle finger up to mock him. San Francisco’s establishment stood by Jones even after a California magazine, New West, owned by Rupert Murdoch, published an exposé of Jones’s beatings of Temple members and financial abuses in August 1977. The article was written by a San Francisco Chronicle reporter and was meant for the Chronicle to publish. But the newspaper killed the story because it didn’t want to alienate Jones, whom it viewed as central to its plans to expand the Chronicle’s circulation in the heavily African American Fillmore District. Jones also managed to avoid investigation and prosecution in part by getting the district attorney to hire as deputy district attorney Jones’s longtime attorney and confidant. Progressives defended Jones against the New West article. At a rally in the summer of 1977, Willie Brown said, “When somebody like Jim Jones comes on the scene, that absolutely scares the hell out of most everybody occupying positions of power in the system.” Angela Davis sent a radio message broadcast over the cult’s compound, Jonestown, in Guyana. “I know you’re in a very difficult situation right now,” she said, “and there is a very profound conspiracy designed to destroy the contributions which you have made to the struggle.” After visiting Jonestown, the attorney to the Black Panthers said, “I have seen paradise.” Harvey Milk, too, was tarnished by his association with Jones. In the fall of 1977, Milk wrote to President Carter’s secretary of health, education, and welfare requesting that Social Security checks be sent to elderly Temple members in Guyana. “People’s Temple,” wrote Milk, has “established a beautiful retirement community in Guyana.” In truth, the cult was disintegrating. Jones separated families and lovers, pitted relatives against each other, and forced neighbors to inform on each other. Jones sent people who violated the rules to solitary confinement in “the Box,” an underground cubicle where people were held as prisoners for days on end. Others were drugged. Progressives who had spent thirty years fighting to close prisons and mental hospitals found themselves praising a man who had reproduced their worst practices. In November 1978 a Bay Area congressman flew to Guyana to investigate human rights violations at Jonestown with NBC News. Jones gave the delegation a formal reception at Jonestown. A Temple member surreptitiously passed a note to one of the delegation members, saying he and another member wanted to escape. They fled the next day after a Temple member tried to stab the congressman. Jones didn’t prevent them from leaving but then sent gunmen to fire machine guns at the delegation at the airport, killing the congressman and four others. A few hours later, 907 inhabitants of Jonestown drank Flavor Aid laced with cyanide and died. Two-thirds of the victims were African American and one-third were children. Jones had told them that if they didn’t drink it they would be killed by invading soldiers from a shadowy global military conspiracy intent on imposing fascism and torturing children. As people started crying in grief, Jones scolded them. “Stop these hysterics,” he said. “This is not the way for people who are socialists or communists to die.” Jones’s wife protested the murder of children and had to be forcibly restrained. “We didn’t commit suicide,” said Jones in a tape recording, “we committed an act of revolutionary suicide protesting the conditions of an inhumane world.” Few were as stained by Jonestown as Willie Brown and George Moscone. “Even as the bloated bodies of the dead were removed from the jungle and the wounded were airlifted by the U.S. Air Force to hospitals in the United States,” wrote a historian, “Brown said he had ‘no regrets’ over his association with Jones.” They repeatedly disavowed responsibility. Said Moscone, “it’s clear that if there was a sinister plan, then we were taken in. But I’m not taking any responsibility. It’s not mine to shoulder.” This is Shellenberger at his best: telling us crazy stories from the recesses of San Francisco history, maybe kind of spinning the narration in a way that makes all progressives seem guilty by association, but with the tale itself so gripping that it’s hard to be mad. And Jones wasn’t alone. This was the golden age of San Francisco cults, when (Shellenberger tells us) “more than half of all high school students in the San Francisco Bay Area reported at least one recruiting attempt by a cult member, and 40 percent reported at least three contacts.” This chapter of SF history came to an end in 1978, when Dan White, who had just resigned from San Francisco’s Board Of Supervisors (ie City Council) entered City Hall through a window and assassinated Mayor Moscone and fellow Supervisor Harvey Milk, then successfully got charges reduced to manslaughter through a legal manuever that has gone down in history as “the Twinkie Defense” (realistically the defense was that he was depressed, but reporters seized on a comment that implied it was because he ate too many Twinkies). Everything about 1970s San Francisco was like this. With the Mayor and his right-hand-man both dead, San Francisco leadership ended up in the hands of previously second-tier politician Dianne Feinstein. Feinstein was what passed for a moderate in 1970s SF (which meant she had been targeted for assassination by various left-wing groups - she survived when a bomb left on her windowsill failed to explode). In Shellenberger’s telling, she managed to clean up some of the mess and restore a semblance of normalcy. San Francisco never forgave her. Moscone - voting fraud committer, underage sex enjoyer, and Jim Jones’ bff - is beloved as a martyr in today’s SF, but (the book points out) Feinstein is so loathed that in 2021 the Board of Education voted to rename Dianne Feinstein Elementary School. The Moscone Center is 2 million square feet and can fit about 10,000 people. Not to be confused with the Moscone Recreation Center, Moscone Station, or Moscone Elementary School. Meanwhile, all Dianne Feinstein got was one lousy elementary school and the Tithonus package of eternal life without eternal youth. Claim 8: The Intolerant Left Shuts Down Debate On These Issues Another one that’s probably hard to do a randomized controlled trial on. You could probably predict that this one was coming - it’s a necessary narrative beat in this genre of book. I think this beat is good. My impression is that people who aren’t themselves public figures disagreeing with left-wing ideas still don’t understand how scary it is and how much hate you get. Maybe now that 2/3s of every political essay written over the past five years is about this topic, people will finally get it through their thick skulls that it exists and is bad. I would also note that “traumatizing the sorts of people who write popular books about politics, in a such a way that they feel compelled as a sort of self-therapy to write page after page telling readers how angry they should be at you and your whole coalition” isn’t great political praxis. I would like people to figure this out and stop doing it. Anyway, Shellenberger is doing his part in this effort: In 2001, the San Francisco Coalition on Homelessness wheat-pasted posters of a fake front-page San Francisco Chronicle across town. Just beneath the masthead a large headline read “Fuck the Homeless!” right above a picture of San Francisco mayor Willie Brown laughing. Below his photo was the headline “Save the Tourists.” Progressives level the same charges at people thirty years later. “Because of some of the stuff I say,” said a community activist in Seattle’s historically black Capitol Hill neighborhood, “people say, ‘Oh, she’s not for them.’ But I have a heart for homeless and mentally ill. Most of my family works with the mentally ill.” Noted a Chronicle journalist in 2017, “Inevitably, homeless advocates and others will say, ‘You’re not compassionate,’” in response to stories about homeless encampments. “They called me a racist,” said Tom. “They accused me, a guy who used to be homeless, of demonizing the homeless, because I’m asking for accountability.” I found myself similarly accused. In 2019, after I published an article for Forbes about the homeless crisis, a progressive homeless activist accused me on Twitter of having written my article to “make money off of a fear tactic” of “fueling hatred [and] even increasing violence against homeless people.” After I asked the former San Francisco supervisor for the Tenderloin neighborhood, former mayoral candidate Jane Kim, how such a progressive city ended up with so much suffering, she said, “My concern, Michael, just to be very honest, is that when that kind of messaging goes out, violence against people who are unhoused goes up.” […] I soon discovered in my research that I was hardly the first person that progressive elected officials and homelessness advocates had accused of fomenting violence against unhoused people. Many others had been criticized for far worse over the years, including San Francisco’s highest elected officials. “The criticism [by progressive homelessness advocates] was heavy, political and personal,” wrote former mayor Willie Brown in his 2008 memoir. “People accused me of abandoning the problem when I was working daily to try and get a solution going. It was brutal. . . . I had become demonized, and my own efforts belittled.” It is notable that the result of such personal attacks is to frighten off people seeking to change, and perhaps improve, the situation. “The problem” of homelessness, concluded Mayor Brown within nine months of entering office, “may not be solvable.” And [Quoting Chris Rufo]. “The chief of psychiatry in a public hospital system in one of the largest California cities told me, ‘I know for a fact, and all of my colleagues know, that what we actually need to deal with the problem in the biggest cities in California is long-term residential secure psychiatric care. But I can’t say that publicly because I would be disemboweled by the activist left. My job would be in jeopardy. My reputation would be in jeopardy. My whole life would get turned upside down for even broaching the subject of expanding secure mental health facilities and compulsory mental health treatment.’ And I said, ‘So what’s the solution?’ and this person said, ‘We muddle through.’” And: In San Francisco, radical left activists protested [African-American] Mayor London Breed in front of her home. Breed said the protesters were “all white people. But that didn’t bother me as much as the taunting of me coming outside with firework torches in their hands looking like what used to happen when the KKK would show up to black people’s houses to burn their houses down.” While I was reading the book, I came across this tweet, which suggests that being unimpressed with SF’s lefty homeless activist scene is not limited to Michael Shellenberger: Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
Claim 9: European Cities Like Amsterdam Successfully Solved Their Own Drug And Homelessness Problems By Doing The Opposite Of SF Shellenberger bases his plan to solve these problems on ideas that he says were pioneered in Amsterdam and spread to other European cities. In the 1980s, Amsterdam had the kinds of problems San Francisco deals with now: open-air drug markets, overdose deaths, homelessness, and crime. But in the 90s, they admitted they had a problem and took decisive action: What’s the secret?” I asked him. “Amsterdam has decriminalized marijuana and many other drugs but I haven’t seen any homeless. What is San Francisco doing wrong?” Rene said that in the 1980s, the Zeedijk neighborhood in Amsterdam was a lot like the Tenderloin [the worst part of San Francisco] today. There was open-air drug use, particularly of heroin, and needles strewn about, as well as crime. People started to flee the neighborhood, worsening its slum conditions. Homeless people squatted in abandoned buildings. “We had ghettos where it was not safe to go,” said Rene, who started working in the neighborhood as a nurse in 1985. It was considered a “no go” zone. “We had a lot of people from abroad who came to Amsterdam because our heroin was so good. But our heroin was so good that they died from it.” At first the city tried a “helping approach” exclusively, offering addicts clean needles, methadone, and other forms of help without any law enforcement, but it didn’t work. “In the eighties we just wanted to help people,” said Rene. “We started with methadone programs and medical treatment. We did a lot of work without much of a carrot and a stick. It was really a disappointment. They just used the methadone to stay addicted. They dealt drugs and committed other crimes. They lied and cheated about it. We were just supporting a different kind of market. We had to learn the hard way [...] The Amsterdam City Council asked the Amsterdam Municipal Health Service to develop a strategy to deal with “unmotivated drug users”...The police broke up the open-air drug scene and health workers were on hand to offer methadone, treatment, and shelter. The police broke up gatherings of more than four or five users, but did not treat personal and private use as a crime. Officers ticketed violators, and if users did not pay their fines, which was frequent, the courts ordered arrests, and sentenced individuals to follow a treatment plan or face incarceration. “For every individual homeless person, we make a plan,” said Rene. “We made tens of thousands of those plans.” Plans are overseen by a caseworker and a team that may include a psychiatrist, shelter provider, service provider, judge, employer, parole officer, and police officer. “You need people in the police and health department working together,” he said. What Amsterdam did was the same as other major European cities. Lisbon, Frankfurt, Vienna, and Zurich all dealt with their open-air drug markets, using a combination of law enforcement and social services. Crucially, Amsterdam and other European cities prevented services from being concentrated in a single neighborhood, since their concentration often enables an open-air drug scene to thrive [...] The efforts worked. “We had several thousand people who were addicted to heroin in the eighties and nineties,” said Rene. “Many died. Today we have four or five hundred people addicted to methadone. And we have about 120 in Amsterdam who we supply heroin to on a medical basis because methadone doesn’t work for them. They have to use heroin.” The Amsterdam strategy goes something like: Break up open-air drug markets and anywhere that more than 4-5 drug users are congregating. Yes, people can just use their drugs in private, but this is legitimately better. Open-air markets normalize drugs with their blatantness, and make it hard to quit for the same reason it’s hard to diet if your partner leaves boxes of donuts out in the house every day.
A minor note of discord: this study characterized Amsterdam’s successful drug program as “harm reduction”, and its conclusion section is titled “Harm Reduction Works”. Shellenberger usually uses “harm reduction” to mean the soft-on-crime policies that don’t do what Amsterdam did. For example, here he points out that Amsterdam has fewer than 130 people using safe injection sites (a typical element of harm reduction strategies). But I gather this is for heroin only; they have many more people on methadone. Most people would also classify methadone treatment as a form of harm reduction. I think this is probably just a semantic quibble and we shouldn’t worry too much about it, but it threw me for a loop here. In any case, whatever harm reduction is or isn’t involved, it’s definitely true that law enforcement breaking up open-air drug markets was a big part of the program.
methamphetamine

methamphetamine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "methamphetamine crosses the blood-brain barrier more effectively than unsubstituted amphetamine". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
methamphetamine
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
In the 1950s, a shady outfit called Obetrol Pharmaceuticals made a popular over-the-counter diet pill called Obetrol. If you're familiar with any of: the 1950s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?" and the answer is yes, loads of them. Obetrol was a mix of four different amphetamine salts: racemic amphetamine sulfate, dextroamphetamine sulfate, methamphetamine saccharate, and methamphetamine hydrochloride. Why did they need four different kinds of speed? I'm not sure. The uncharitable explanation is: for the same reason Dr. Nick's Cure-All Home Remedy has twelve different herbs, ie customers think things with more ingredients are better.
By the 1970s, people figured out meth was bad, so Obetrol replaced their two methamphetamine salts with two more kinds of non-methylated amphetamine. But the FDA continued to crack down, and although the historical paper trail goes kind of dark, it looks like Obetrol had disappeared by the 1980s.
What's the catch? Desoxyn is methamphetamine. The FDA and DEA discourage doctors from prescribing it, but it's still technically legal with an MD's prescription, and there are still some doctors who will use it for the most refractory cases. It is officially indicated for ADHD and obesity (really!), but gets used off-label for narcolepsy and various sleep disorders.
Microsoft Excel

Microsoft Excel is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 26, 2025 and July 26, 2025. The archive places it in contexts such as "a cool hidden feature of Microsoft Excel where it open UTF-8 encoded CSVs". It most often appears alongside 4chan, ACX, ACX.

Reference entry
Microsoft Excel
Mention count
1
Issue count
1
First seen
July 26, 2025
Last seen
July 26, 2025
July 26, 2025 · Original source
Complexity of thought – Perhaps the most important feature distinguishing the ACX Commentariat from other, lesser, blogs is that some really smart people comment here and give novel and well-nuanced takes on a topic. If this ever disappeared it would not matter about any of the other three features, because the Commentariat would effectively be dead anyway. To me, these broad categories represent the unique and positive features of the SSC/ACX Commentariat, and the extent to which they are present is a reasonable indicator of comment section quality, especially if they are all present at the same timepoint and that timepoint happens to line up with peak engagement in 2016 (this is foreshadowing). To generate data on the ACX Commentariat, I scraped the comments section of every post Scott has made since 2013. The Old Ones whisper of a blog that existed before even Slate Star Codex, but since I’m not 100% certain we’re encouraged to talk about the older blog (and nobody dates the golden era of Scott’s writing to pre-2013 anyway) I kept my scraping to just the two websites we’re definitely allowed to talk about; Slate Star Codex (SSC) and Astral Codex Ten (ACX). The main points of failure with my scraping were Subscriber-only threads (which my algorithm virtuously refused to read as it wasn’t a subscriber) and battling with the Substack UI to get all the comments to load for me simultaneously on larger threads. Nevertheless, between my incompetent code and the jaunty Substack UI I only dropped a few comments on even very long threads, so I figured the data scrape would be adequate for the use-case I had for it. I then used a bunch more janky code (some written by me, some written by ChatGPT) to try and quantify the levels of depth, freedom, politeness and complexity of each comment. I captured 2460 individual posts, and approximately 1.8m comments. Of the 24,486 unique comment authors, around 40% have made only one comment to the blog. The most prolific poster is the irrepressible Deiseach, at 20,685 contributions. Deiseach is also the only commentor to have made a comment on both the first post in my sample and the last, so has been with the blog a very long time! Only one other commentor has made more contributions than Scott (11,249), and this is John Schilling (11,607). The quality of data on individual users is not great for the ACX era (Substack seems to record missing author data in a few different ways, and sometimes swallow data for no reason) but I’m happy to give the rank ordering of anyone else who cares to know their specific level of clout in this niche community - I myself am the 799th most prolific contributor to the comments section (225 comments). I’m also delighted to share my raw data with anyone interested – the summary statistics per post are here. The scraped comments themselves are about 2Gb so I don’t know where I can host them but if anyone has any ideas (and Scott doesn’t mind) I’ll share them too. I know that some of the post titles seem to have turned into hieroglyphics, but as far as I can tell it is cosmetic only and won’t affect any of the actual data – it is a symptom of a cool hidden feature of Microsoft Excel where it open UTF-8 encoded CSVs in a way that garbles special characters for no particular reason. Considering each of these factors in turn: Depth of engagement with a topic
microwave

microwave is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 06, 2024 and August 06, 2024. The archive places it in contexts such as "and produced... the microwave". It most often appears alongside AI, altruism, America.

Reference entry
microwave
Mention count
1
Issue count
1
First seen
August 06, 2024
Last seen
August 06, 2024
August 06, 2024 · Original source
I’m skeptical of this argument. America’s been at peace since World War II (foreign adventures like Vietnam haven’t substantially changed our national experience) and produced the computing revolution, the Internet, AI, the moon landing, the Human Genome Project, antiretrovirals, the microwave, the laser, the smartphone, and the reusable rocket. During that time, Iraq has had approximately eight major wars and didn’t even get a cuckoo clock out of it.
midazolam

midazolam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 14, 2023 and November 14, 2023. The archive places it in contexts such as "Sometimes researchers try to use an “active placebo” like midazolam - a drug that makes you feel weird and floaty". It most often appears alongside ketamine, ketamine, MADRS.

Reference entry
midazolam
Mention count
1
Issue count
1
First seen
November 14, 2023
Last seen
November 14, 2023
November 14, 2023 · Original source
Ketamine is a dissociative drug - it produces weird drug effects like feelings of bodylessness and ego death. Recent research suggests it’s a powerful antidepressant. Usually we would try to run placebo-controlled trials. But it’s hard to run a placebo controlled trial of a dissociative. Either you feel bodylessness and ego death (in which case you know you’re getting the real drug) or you don’t (in which case you know you’re in the placebo group). Sometimes researchers try to use an “active placebo” like midazolam - a drug that makes you feel weird and floaty. But weird and floaty feels different from bodyless and ego-dead.
And my patients’ experience is that it works even at low doses that produce no dissociative or ego death effect. I usually prescribe it at about 70 mg intranasal. Some of my patients report feeling a little drunk or giddy on this amount, but nothing like the k-hole that people report at the really high levels. Other patients report nothing at all, but still feel better. This makes me doubt that you necessarily need an study under anaesthesia to control for dissociative effects. A simple midazolam active placebo would work fine. But also, SSRI studies have shown that active placebos don’t really work any better than inactive placebos. This might be more true for SSRIs (which have boring side effects) than ketamine (which at least sometimes has exciting ones). But it means that when evaluating normal ketamine studies (which risk confounding through inactive placebos) vs. this study (which risks confounding through anaesthesia and surgery), I’m more likely to just go with the normal ones.
I admit this study is awkward, and I find it a little confusing. But I plan to stick with my previous belief that ketamine has an average effect size of 0.5 - 0.7 and is a good antidepressant for some (though not all) people. If the ketamine-is-just-a-placebo crowd want to convince me otherwise, I would update hardest on a trial of 70 mg intranasal ketamine on one side vs. midazolam on the other, x4 weeks, where neither side was able to guess which group they were in, but the drugs were still taken in a fairly normal environment.
Midjourney 5

Midjourney 5 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 30, 2023 and August 30, 2023. The archive places it in contexts such as "Then Midjourney 5 came out and started behaving a lot better". It most often appears alongside 2020 election, ACX, Aella.

Reference entry
Midjourney 5
Mention count
1
Issue count
1
First seen
August 30, 2023
Last seen
August 30, 2023
August 30, 2023 · Original source
Midjourney 5 had not come out, and so we were using 4 to generate some characters for our app.
Then Midjourney 5 came out and started behaving a lot better. Feet were pretty trivial to generate (and hands reliably had 5 fingers) and the excitement of seeing them quickly wore off.
Mifepristone

Mifepristone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 01, 2025 and July 01, 2025. The archive places it in contexts such as "Mifepristone (aka RU-486, the “abortion pill”)". It most often appears alongside Afrobarometer, AGI, AI 2027.

Reference entry
Mifepristone
Mention count
1
Issue count
1
First seen
July 01, 2025
Last seen
July 01, 2025
July 01, 2025 · Original source
19: Mifepristone (aka RU-486, the “abortion pill”) in early-stage investigation as a depression treatment.
Milady

Milady is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 04, 2023 and September 04, 2023. The archive places it in contexts such as "Milady is some kind of NFT thing". It most often appears alongside Africa, Beyabu, Bildod.

Reference entry
Milady
Mention count
1
Issue count
1
First seen
September 04, 2023
Last seen
September 04, 2023
September 04, 2023 · Original source
According to this article, State Senator Bill Dodd2 worries that a new city might have an “impact on agricultural production”, “harm Travis Air Force Base”, and cause “suburban sprawl”. And if they defeat all these people and win the local election, anyone who is against them can still lodge the normal CEQA and NEPA objections that have gummed up most large building projects in California over the past fifty years. And if they defeat those, they still have to build the city. Rep. Garamendi is skeptical, saying3: I think it’s pie in the sky. We know this area. I've talked to a very seasoned developer in California and asked what do you think of that? He said, keep in mind that the land is about 1/10th of the actual cost of building the city. You've got streets and roads and sewer systems and sanitation. They even want to build a concert hall. And if they manage that, what do they do about their own citizens? California allows a local government form called a “charter city”, but I don’t think you can get away with being actually undemocratic. So once 10,000 people live in their town, what’s to stop those people from becoming NIMBYs and voting against further growth? I assume there’s some answer to this question, since people have built successful company-owned planned cities in California in the past (eg Irvine). I’m just not sure what it is. Could their city charter ban zoning? Could they have some sort of super-powerful city manager paired with a very weak democratic council? Could they build everything first, and only invite people to move in after they’re done? Of course there are prediction markets: This is the only one with more than 15 traders, but go here to see the smaller ones; I’ll try to highlight them later if they get big enough to be credible. Also, some people asking the important questions: The Paradox Of Praxis You can think of new city projects as existing on a spectrum: Usually the ones on the left are more fun to talk about, but the ones on the right are more fun to invest in. The paradox of Praxis is that to all appearances, they’re several miles off the left side of this graph. No amount of reading starry-eyed overly-ambitious Silicon Valley ad copy can prepare you for how over-the-top Praxis is. Praxis has a manifesto with phrases like “glory in death by a light brighter than a thousand suns" and "atrophied bodies submerged in gel, fed a synthetic bug paste". Praxis holds parties in classical-music-filled candlelit lofts where they ask participants about “Janusian thinking”. Praxis has a website www.terrifyingangel.com which is just a YouTube video on the idea of meaning throughout human history, plus a resignation letter you can send to your boss when you quit to join Praxis. Seen on the Praxis founder’s Twitter account. Milady is some kind of NFT thing, otherwise it makes as much sense to me as it does to you. But the other half of the paradox is the constant rumors that they’re competent and have some kind of good plan. These are spoken only in hushed whispers, I don’t know the details. But in 2021, they raised $4 million in a seed round from well-regarded venture capitalists whose investments usually make money. In 2022 they raised another $15 million in a Series A round from . . . okay, partly from Sam Bankman-Fried and Three Arrows Capital, two notorious crypto scammers. But you would think scammers would be extra careful not to invest their own money in scams! Also, they recently signed on David Weinreb, a completely normal (and well-regarded) city planner person. What’s the strategy that both involves both Milady Raves and lots of competent people agreeing you’re a good investment? One strategy is something like: buy some land somewhere. Build some houses and streets. Convince digital nomads to move there on the grounds that you are very cool and visionary. Do some cool and visionary seeming things, or at least throw some really good raves. Other digital nomads get jealous and move there too. Sell parcels of land to these people, get rich, pay back your investors. And then who knows, maybe create a new civilization that redefines what it means to be human. Consider Elon Musk. Elon Musk is good at certain business-related skills. But that’s not the essence of Elon Musk. The essence of Elon Musk is that he’s a Visionary who can bring the Glorious Future. We know this because he’s a crazy person who says stuff that doesn’t really make sense. When Elon Musk buys a company, its value goes up - maybe partly because people expect Musk to make good business decisions, but also partly because now the company is part of Musk’s Glorious Future, and therefore exciting. Employees, customers, and investors all get excited and reinforce each other in a virtuous circle. And although Musk might not always accomplish the exact Glorious Future future he promises, his companies do well and make money, because having motivated employees, star-struck customers, and willing investors is a great combination. Elon Musk has an aura of destiny because he succeeded at his first several companies. Dryden Brown of Praxis Society, lacking a Paypal Mafia to join, is trying to hack together an aura of destiny out of raves and angel-related videos. So far it seems to be going pretty okay. Prospera Sues Honduras For 2/3 Of Its National Budget To refresh: in the mid-2010s Honduras’ pro-market government created ZEDEs - businesses that bought up unoccupied land could start their own districts with their own preferred legal system in exchange for bringing in investment. The government knew businesses wouldn’t invest long-term if the next government could just cancel the agreement and seize all of their stuff, so they fortified the law with as much protection as possible. It would take a long constitutional amendment process to repeal, and ZEDE investors might be able to object to any changes under international investment treaties. Lured by these protections, three companies started ZEDEs, including a big high-profile one called Prospera. In early 2022, a socialist government took power, and started trying their best to destroy the ZEDEs. They started the constitutional amendment process (they seem to think they’ve finished it, but a Prospera rep I talked to believe they have to hold another vote by the end of this year, something I see no signs of them doing) and have been harassing and stonewalling existing ZEDEs. One ZEDE, Orquidea, shut down immediately. A second, Ciudad Morazan, seems to still be operating but I cannot figure out exactly how or why. Prospera has been most vocal in its opposition, and sued Honduras for $11 billion in the World Bank’s court of investment arbitration. (Prospera has only spent about $100 million so far, so it’s unclear why they deserve 100x that in penalties. Also $11 billion is “two-thirds of the 2022 Honduran national budget”, and forcing Honduras to pay it would cause national catastrophe. This might be more of a highball offer than a number they actually expect to get.) This article (poorly translated from Spanish, sorry) has the most information. It suggests Honduras believes they signed onto the investment treaties “with reservations”, ie conditional on being allowed to do things like shut down ZEDEs, and that therefore the suit is meaningless and they will not defend themselves. Although the magazine is on the government’s side of the overall issue, it suggests they didn’t actually sign on with reservations, that the country’s lawyers might just have no idea what they’re talking about, and that their bold strategy of refusing to defend themselves will not pay off. In contrast, Prospera has prestigious lawyers specializing in exactly this area, so things aren’t looking good for the government. Honduras seems to recognize this and is threatening to withdraw from ICSID, the international investment treaty that governs such disputes. This wouldn’t be completely unprecedented - Venezuela, Bolivia, and Ecuador have also done this. But ICSID rules say that withdrawing from ICSID, while it might help prevent future cases against you, doesn’t cancel existing cases, and wouldn’t protect Honduras against Prospera’s claim. (How would ICSID collect against Honduras if they lost? I don’t know, but I assume the global financial order has some way to make your life worse if you defy it.) I think everyone is hoping Honduras realizes that cancelling a flourishing economic zone that’s bringing lots of investment into the country at no cost to them - just isn’t worth taking an $11 billion loss, cancelling international treaties, and scaring off future investment. But who knows how these people think? In other Prospera news: Prospera announces another $36 million in recent investment, which I take as evidence that VCs with good lawyers and research departments also think its case is very strong.
Seen on the Praxis founder’s Twitter account. Milady is some kind of NFT thing, otherwise it makes as much sense to me as it does to you. But the other half of the paradox is the constant rumors that they’re competent and have some kind of good plan. These are spoken only in hushed whispers, I don’t know the details. But in 2021, they raised $4 million in a seed round from well-regarded venture capitalists whose investments usually make money. In 2022 they raised another $15 million in a Series A round from . . . okay, partly from Sam Bankman-Fried and Three Arrows Capital, two notorious crypto scammers. But you would think scammers would be extra careful not to invest their own money in scams! Also, they recently signed on David Weinreb, a completely normal (and well-regarded) city planner person. What’s the strategy that both involves both Milady Raves and lots of competent people agreeing you’re a good investment? One strategy is something like: buy some land somewhere. Build some houses and streets. Convince digital nomads to move there on the grounds that you are very cool and visionary. Do some cool and visionary seeming things, or at least throw some really good raves. Other digital nomads get jealous and move there too. Sell parcels of land to these people, get rich, pay back your investors. And then who knows, maybe create a new civilization that redefines what it means to be human. Consider Elon Musk. Elon Musk is good at certain business-related skills. But that’s not the essence of Elon Musk. The essence of Elon Musk is that he’s a Visionary who can bring the Glorious Future. We know this because he’s a crazy person who says stuff that doesn’t really make sense. When Elon Musk buys a company, its value goes up - maybe partly because people expect Musk to make good business decisions, but also partly because now the company is part of Musk’s Glorious Future, and therefore exciting. Employees, customers, and investors all get excited and reinforce each other in a virtuous circle. And although Musk might not always accomplish the exact Glorious Future future he promises, his companies do well and make money, because having motivated employees, star-struck customers, and willing investors is a great combination. Elon Musk has an aura of destiny because he succeeded at his first several companies. Dryden Brown of Praxis Society, lacking a Paypal Mafia to join, is trying to hack together an aura of destiny out of raves and angel-related videos. So far it seems to be going pretty okay. Prospera Sues Honduras For 2/3 Of Its National Budget To refresh: in the mid-2010s Honduras’ pro-market government created ZEDEs - businesses that bought up unoccupied land could start their own districts with their own preferred legal system in exchange for bringing in investment. The government knew businesses wouldn’t invest long-term if the next government could just cancel the agreement and seize all of their stuff, so they fortified the law with as much protection as possible. It would take a long constitutional amendment process to repeal, and ZEDE investors might be able to object to any changes under international investment treaties. Lured by these protections, three companies started ZEDEs, including a big high-profile one called Prospera. In early 2022, a socialist government took power, and started trying their best to destroy the ZEDEs. They started the constitutional amendment process (they seem to think they’ve finished it, but a Prospera rep I talked to believe they have to hold another vote by the end of this year, something I see no signs of them doing) and have been harassing and stonewalling existing ZEDEs. One ZEDE, Orquidea, shut down immediately. A second, Ciudad Morazan, seems to still be operating but I cannot figure out exactly how or why. Prospera has been most vocal in its opposition, and sued Honduras for $11 billion in the World Bank’s court of investment arbitration. (Prospera has only spent about $100 million so far, so it’s unclear why they deserve 100x that in penalties. Also $11 billion is “two-thirds of the 2022 Honduran national budget”, and forcing Honduras to pay it would cause national catastrophe. This might be more of a highball offer than a number they actually expect to get.) This article (poorly translated from Spanish, sorry) has the most information. It suggests Honduras believes they signed onto the investment treaties “with reservations”, ie conditional on being allowed to do things like shut down ZEDEs, and that therefore the suit is meaningless and they will not defend themselves. Although the magazine is on the government’s side of the overall issue, it suggests they didn’t actually sign on with reservations, that the country’s lawyers might just have no idea what they’re talking about, and that their bold strategy of refusing to defend themselves will not pay off. In contrast, Prospera has prestigious lawyers specializing in exactly this area, so things aren’t looking good for the government. Honduras seems to recognize this and is threatening to withdraw from ICSID, the international investment treaty that governs such disputes. This wouldn’t be completely unprecedented - Venezuela, Bolivia, and Ecuador have also done this. But ICSID rules say that withdrawing from ICSID, while it might help prevent future cases against you, doesn’t cancel existing cases, and wouldn’t protect Honduras against Prospera’s claim. (How would ICSID collect against Honduras if they lost? I don’t know, but I assume the global financial order has some way to make your life worse if you defy it.) I think everyone is hoping Honduras realizes that cancelling a flourishing economic zone that’s bringing lots of investment into the country at no cost to them - just isn’t worth taking an $11 billion loss, cancelling international treaties, and scaring off future investment. But who knows how these people think? In other Prospera news: Prospera announces another $36 million in recent investment, which I take as evidence that VCs with good lawyers and research departments also think its case is very strong.
mirtazapine

mirtazapine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
mirtazapine
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
If one of these doesn’t work, try the other. If neither of them work, and you’re feeling optimistic, you might want to try a different SSRI, maybe sertraline. If that doesn’t work, move on to second-line treatments. Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline.
Mirtazapine is a mediocre antidepressant which is very good at making people hungry and sleepy. If you don’t want to be hungry and sleepy, this is definitely not the antidepressant for you. If you do want to be hungry and sleepy, maybe because your symptoms include insomnia and loss of appetite, mirtazapine is great. Most people are able to take it at night, get a normal night of sleep, and not be excessively sleepy when they wake up in the morning, but if that’s not you then you might have to switch to something else.
Mistral

Mistral is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa"; "twelve LLMs - including ... Mistral"; "the only AI is a Mistral instance on the smartphone of some billionaire". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
Mistral
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
Are these the data I’ve been trying to get for years - which forecasting platforms beat which others? I don’t think so - Metaculus’ good Briar score only means it performs well on Metaculus’ questions, which might be easier or harder than some other platform’s questions. Can we use the Halawi et al AI as a fixed comparison point, since it’s always the same skill level? I’m not sure - it trained on each of these markets for the style of question that’s in each market, so it might be biased. Still, these numbers are all about where I would expect them to be, except maybe Polymarket, which does better than I would have expected. But the crowd still beats the AI, right? Halawi et al object that humans can forecast only when they feel like it - you can bet on a prediction market question you feel confident on, and avoid one you don’t. When they let their AI forecast only on those questions where it’s most likely to do well (eg those with lots of relevant news articles), it very slightly outperforms the human crowd. As AI gets better, will it naturally beat humans in forecasting? Halawi et al say this won’t be trivial. They find a version of their system based off GPT-3.5 is only very slightly worse than the final version built off GPT-4. This suggests a forecasting AI built off GPT-5 or 6 might get only small improvements. The second team is Tetlock et al. They start from the same place as Halawi - out-of-the-box LLMs aren’t good at forecasting. They’re more scathing about this than Halawi was - they argue that out-of-the-box models do worse than predicting 50% for everything (this was close to true of human forecasters in the ACX tournament). Instead of increasing quality, Tetlock increases quantity. He wants to do wisdom of crowds, where the crowd is a bunch of different LLMs. So he gets twelve LLMs - including Bard, GPT, Claude, Mistral, PaLM, LLaMa, some Chinese models I’d never heard of, and a couple of variations on these bases - asks them to predict questions, and averages the results. Remember, you gotta prompt your model with “you are a smart person”, or else it won’t be smart! The results: Next, we compare the LLM crowd performance to that of the human crowd for our second hypothesis, directly putting the two crowd-aggregation mechanisms head-to-head. To do this, we use the same LLM crowd average as before (taking the median LLM prediction on each question and averaging up the Brier scores across questions). We compare this to the average of median human predictions on the same questions. In our preregistered analysis, we fail to find statistically significant differences between the LLM crowd’s mean Brier score of M=0.20 (SD=0.12) and that of the human crowd, M=0.19 (SD=0.19), t(60) = 0.19, p = 0.850 Their study was much smaller than Halawi’s (31 questions vs. 3,672), so I don’t think this result (nonsignificant small difference) should be considered different from Halawi’s (significant small difference). Still, it’s weird, isn’t it? Halawi used a really complicated tower of prompts and APIs and fine-tunings, and Tetlock just got more LLMs, and they both did about the same. I have two questions after reading these results: Did they actually do the same, or is this just a function of the small sample size in Tetlock and the non-head-to-head comparison?
I found this really interesting because the skeptics’ case for doubt is so different from my own. The main reason I’m 20% and not 100% p(doom) is that I think AIs might become power-seeking only very gradually, in a way that gives us plenty of chances to figure out alignment along the way (or at least pick up some AI allies against the first dangerous ones). If you asked me for my probability that humans are still collectively more powerful/important than all AIs in 2450, I’d get confused and say “You mean, like, there was WWIII and we’re all living in caves and the only AI is a Mistral instance on the smartphone of some billionaire in a bomb shelter in New Zealand?”
Model 3

Model 3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2023 and September 18, 2023. The archive places it in contexts such as "Their structures up to the Model 3 are quite inefficient". It most often appears alongside 787, adderallposting, ADL.

Reference entry
Model 3
Mention count
1
Issue count
1
First seen
September 18, 2023
Last seen
September 18, 2023
September 18, 2023 · Original source
But out of all of that, my biggest take-away was that Teslas..... just aren't very good? Their structures up to the Model 3 are quite inefficient and don't have great rigidity. The dimensional variation is shocking (far beyond even SBU, IYKYK). The hang-on parts are generally relatively poorly performing on their own. They can't touch our structural or powertrain durability tests. Rate and handling is bad, ergonomics fails to meets package targets, NVH and sound quality are poor, and we pay JD Power far too much to find out just how bad the quality numbers are (hilariously bad). I don't think it's an exaggeration to say that most other OEMs can't make a Tesla, because our systems and processes prevent us from releasing something that half-baked.
Model S

Model S is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "Musk opted to [reduce the Model S’ weight]"; "Like the controversial door handles on the Model S, the Model X’s doors have become one of its most striking features"; "we needed to ask Elon for an extra two weeks and more money to build out another version of the Model S". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Model S
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Musk opted to [reduce the Model S’ weight] by making the body . . . out of lightweight aluminum instead of steel.
When Tesla’s engineers first heard about the falcon-wing doors, they cringed. Here was Musk with another crazy ask. “Everyone tried to come up with an excuse as to why we couldn’t do it,” Javidan said. “You can’t put it in the garage. It won’t work with things like skis. Then, Elon took a demo model to his house and showed us that the doors opened. Everyone is mumbling, ‘Yeah, in a fifteen-million-dollar house, the doors will open just fine.’” Like the controversial door handles on the Model S, the Model X’s doors have become one of its most striking features and the thing consumers talk about the most. “I was one of the first people to test it out with a kid’s car seat,” Javidan said. “We have a minivan, and you have to be a contortionist to get the seat into the middle row. Compared to that, the Model X was so easy. If it’s a gimmick, it’s a gimmick that works.”
Tesla employees developed similar techniques to their counterparts at SpaceX for dealing with Musk’s high demands. The savvy engineers knew better than to go into a meeting and deliver bad news without some sort of alternative plan at the ready. “One of the scariest meetings was when we needed to ask Elon for an extra two weeks and more money to build out another version of the Model S,” Javidan said. “We put together a plan, stating how long things would take and what they would cost. We told him that if he wanted the car in thirty days it would require hiring some new people, and we presented him with a stack of resumes. You don’t tell Elon you can’t do something. That will get you kicked out of the room. You need everything lined up. After we presented the plan, he said, 'Okay, thanks.’ Everyone was like, ‘Holy shit, he didn’t fire you.’”
Model X

Model X is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "The book’s two main examples were the “falcon-wing” doors on the Model X"; "The Model X has what Musk coined as “falcon-wing doors.”". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Model X
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Like with engineering, Musk is hands-on in the design of his products, ie he comes up with wild ideas and demands they be implemented over everyone else’s objections. The book’s two main examples were the “falcon-wing” doors on the Model X, and the classic Tesla door handles that are flush with the car until you coax them out.
With the Model X, Musk again turned to his role as a dad to shape some of the flashiest design elements of the vehicle. He and [lead designer] von Holzhausen were walking around the floor of an auto show in Los Angeles, and they both complained about the awkwardness of getting to the middle and back row seats in an SUV. Parents who have felt their backs wrench while trying to angle a child and car seat into a vehicle know this reality all too well, as does any decent-sized human who has tried to wedge into a third row seat. “Even on a minivan, which is supposed to have more room, almost one-third of the entry space is covered by the sliding door,” von Holzhausen said. “If you could open up the car in a way that is unique and special, that could be a real game changer.
We took that kernel of an idea back and worked up forty or fifty design concepts to solve the problem, and I think we ended up with one of the most radical ones.” The Model X has what Musk coined as “falcon-wing doors.” They’re hinged versions of the gull-wing doors found on some high-end cars like the DeLorean. The doors go up and then flop over in a constrained enough way that the Model X won’t rub up against a car parked close to it or hit the ceiling in a garage. The end result is that a parent can plop a child in the second-row passenger seat without needing to bend over or twist at all.
Model X Founders' Edition

Model X Founders' Edition is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2023 and September 18, 2023. The archive places it in contexts such as "I saw a Model X Founders' Edition fully disassembled on tables". It most often appears alongside 787, adderallposting, ADL.

Mention count
1
Issue count
1
First seen
September 18, 2023
Last seen
September 18, 2023
September 18, 2023 · Original source
Something that probably ought to get talked about more: for large companies, we are among the first few hundred to buy the newest hotness from our competitors. I saw a Model X Founders' Edition fully disassembled on tables, with the welds drilled out and sectioned so we could see every single part. I've done side-by-sides with Teslas and various other vehicles, where we literally will put our part and the competitor part next to each other in a giant warehouse (all of them for a series of vehicles) and do side-by-sides. When you do that, abstract questions of genius kind of fade to the background, and you get to actual real world questions like "is this part good? Is it better than mine? What is it trying to do? How does it try to do them? What does this say about the engineer's constraints? What does this say about the company organization behind it? Where are the organizational seams? Where are the hard points that could not be changed? How do those reflect on my company, my program, what we're trying to do and the things we have to work around?"
Moderna

Moderna is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 10, 2024 and May 10, 2024. The archive places it in contexts such as "Moderna's mRNA-4157 platform also looks good". It most often appears alongside "Most Drugs Are Bad For You", 1123581321, California.

Reference entry
Moderna
Mention count
1
Issue count
1
First seen
May 10, 2024
Last seen
May 10, 2024
May 10, 2024 · Original source
Moderna's mRNA-4157 platform also looks good: https://jakeseliger.com/2024/04/12/moderna-mrna-4157-v90-news-for-head-and-neck-cancer-patients-like-me/, not only in R / M HNSCC, but in melanoma and lung, too. Right now mRNA-4157 is only being tested in the recurrent / metastatic setting, as far as I know, but the logical time to use it is probably when initial surgeries are done: cut the cancer, sequence it, and then vaccine against it to prevent recurrence.
MoonCoin

MoonCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 31, 2023 and January 31, 2023. The archive places it in contexts such as "endorses MoonCoin, and MoonCoin goes up". It most often appears alongside 2022 contest, American Civics Exchange, CFTC.

Reference entry
MoonCoin
Mention count
1
Issue count
1
First seen
January 31, 2023
Last seen
January 31, 2023
  • 2023 January 31, 2023
January 31, 2023 · Original source
Taking Stock Prediction market users really want stocks. “Stock” in this sense means an instrument that measures the status of a person, group, or idea. When their status goes up, the stock goes up. When their status goes down, the stock goes down. It feels like a natural way to bet on things like “I’m bearish on Elon Musk and think everyone else is overestimating him.” It’s hard to turn this vague idea into a real financial instrument. You could try tying it to their Twitter follower count, or Google search trends, or net worth, but none of these exactly track “status”. If Musk commits murder in broad daylight, his search volume will go up, his Twitter follower count will stay about the same, his net worth might not be affected, but his status will have gone way down. The current solution is to make no effort whatsoever to moor stocks to the real world and just hope they work out. This could work! It’s kind of like a Ponzi scheme or crypto token. Some big influencer endorses MoonCoin, and MoonCoin goes up, because MoonCoin has gained status, which means more people will want to buy it, because it’s even more likely that more people will want to buy it later. Crypto tokens keep a fig leaf of “and maybe in the cyberpunk future when all transactions everywhere have switched to crypto this will really pay off”, but over time that fig leaf became increasingly threadbare, and a fun low-stakes instrument like Manifold stocks might do fine without it. But the 0% to 100% prediction scale is a bad match for stocks. If Elon started at 50% in 2000, then when Tesla made it big he surely should have doubled. And that brings him up to 100% and leaves nowhere for him to go. Also, people who bet on Elon Musk in 2000 might be miffed that their prescient choice only doubled their money. Probably the solution is some kind of cardinal number. But which one, and at what scale? Again, the lesson from crypto is that maybe it doesn’t matter. Just start at 10 or something or something and see where it ends up. Manifold leadership isn’t totally resigned yet to having stocks be meaningless Ponzi schemes. If you have a better idea for how to run stocks, leave it in the comments here and they’ll probably see it. CFTC vs. PredictIt Update So far it’s not clear if this means indefinite normal operation, or if they’ll spend the extra time trying to wind existing markets down. The overall chance of them winning their lawsuit remains unchanged at around 25%. PredictIt has gotten some sympathetic news coverage, including from the Washington Post. In the process, the Post tried to get some clarity on what terms of the no-action letter PredictIt violated, apparently without success: @CFTC why they're shutting PredictIt down. They give no real answer, just as in the original withdrawal letter. Closest thing we have to an answer is that they don't want other prediction markets. But why? No sense here at all. washingtonpost.com/lifestyle/2023… ","username":"RichardHanania","name":"Richard Hanania","profile_image_url":"","date":"Tue Jan 24 18:12:59 +0000 2023","photos":[{"img_url":"https://pbs.substack.com/media/FnQbawZaYAAKRws.jpg","link_url":"https://t.co/zeKhe8sjnT","alt_text":null}],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":39,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> @StephenPiment I'm flat appalled the CFTC said \"you violated terms\", but won't tell anyone, @PredictIt included, which ones, and then has big enough balls to try to get the judge to dismiss PI's \"shotgun\" defense. Um, with no info what other case COULD they make?\n","username":"kmett","name":"Edward Kmett","profile_image_url":"","date":"Sun Nov 27 19:01:29 +0000 2022","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":8,"like_count":21,"impression_count":0,"expanded_url":{"url":"https://www.bonus.com/news/cftc-predictit-hearings-coming/","image":"https://substack-post-media.s3.amazonaws.com/public/images/8d5a1d5e-49ee-4294-84cd-eb5a4259bbc3_1200x800.jpeg","title":"Hearings Coming Soon in PredictIt Lawsuit, CFTC Asks to Dismiss","description":"The CFTC is seeking to have the PredictIt lawsuit dismissed, while the plaintiffs want the case fast-tracked due to the shutdown deadline.","domain":"bonus.com"},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> I guess they’ll have to give some kind of explanation during the hearing, right? Related: Richard Hanania has an article on How To Legalize Prediction Markets. The actual advice isn’t very surprising, and mostly boils down to “write letters to the government officials in charge of this”, but like other people I learned something new from the details: In the United States, prediction markets are, with a few minor exceptions, against the law. If you don’t have a legal background, you might think that means that Congress at some point considered the issue, decided people shouldn’t be able to bet on real world events, and passed a law to that effect, which was then signed by the president. But this is not what happened. As with most things, Congress has never directly considered the matter. Rather, prediction markets are illegal due to the discretion of a government agency called the Commodity Futures Trading Commission (CFTC). Why does it have this right? And on what basis has it made prediction markets illegal? […] In 1936, Congress passed and FDR signed the Commodity Exchange Act. In 1974, Congress created the CFTC to enforce the original law, which has been amended on multiple occasions over the years. The CFTC has authority to regulate what are called “derivatives markets.” A derivatives contract derives its value from some kind of underlying asset or benchmark in the real world. The thing to understand about derivatives is that the baseline is that they’re legal. That’s why you can “bet” on the price of oil through a futures contract. The CFTC wasn’t created to ban derivative markets, but to regulate them, though this can involve prohibiting certain kinds of markets altogether. Current law includes the following provision on event contracts, [banning]: activity that is unlawful under any Federal or State law;
Mounjaro®

Mounjaro® is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2025 and March 12, 2025. The archive places it in contexts such as "Tirzepatide (Mounjaro®, Zepbound®)". It most often appears alongside Denmark, DOGE, Eli Lilly.

Reference entry
Mounjaro®
Mention count
1
Issue count
1
First seen
March 12, 2025
Last seen
March 12, 2025
March 12, 2025 · Original source
Tirzepatide (Mounjaro®, Zepbound®)
mRNA-4157

mRNA-4157 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 10, 2024 and May 10, 2024. The archive places it in contexts such as "Moderna's mRNA-4157 platform". It most often appears alongside "Most Drugs Are Bad For You", 1123581321, California.

Reference entry
mRNA-4157
Mention count
1
Issue count
1
First seen
May 10, 2024
Last seen
May 10, 2024
May 10, 2024 · Original source
Moderna's mRNA-4157 platform also looks good: https://jakeseliger.com/2024/04/12/moderna-mrna-4157-v90-news-for-head-and-neck-cancer-patients-like-me/, not only in R / M HNSCC, but in melanoma and lung, too. Right now mRNA-4157 is only being tested in the recurrent / metastatic setting, as far as I know, but the logical time to use it is probably when initial surgeries are done: cut the cancer, sequence it, and then vaccine against it to prevent recurrence.
But that should change! Part of the reason I'm so frustrated by the FDA is that mRNA-4157 and TG4050 should already be available for HNSCC. Instead, they're stuck in trial hell, while HNSCC patients like me suffer recurrences and then die.
Muslim Blocks

Muslim Blocks is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 29, 2024 and February 29, 2024. The archive places it in contexts such as "Islam has Muslim Blocks". It most often appears alongside @BoyanSlat, @eigenrobot, @JackTindale.

Reference entry
Muslim Blocks
Mention count
1
Issue count
1
First seen
February 29, 2024
Last seen
February 29, 2024
February 29, 2024 · Original source
26: Did you know: lots of religions have their own version of LEGO, usually with sets depicting their mythology or temples. Islam has Muslim Blocks, Hinduism has Indic Bricks, and Judaism has Binyan Blocks. But my favorite is Mormonism with - wait for it - Brick’em Young (h/t @seanw_m)
Muzak

Muzak is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 23, 2022 and August 23, 2022. The archive places it in contexts such as "listening to Muzak and eating potatoes". It most often appears alongside 80,000 Hours, abolitionist literature, AI.

Reference entry
Muzak
Mention count
1
Issue count
1
First seen
August 23, 2022
Last seen
August 23, 2022
August 23, 2022 · Original source
MacAskill concludes that there’s no solution besides agreeing to create as many people as possible even though they will all have happiness 0.001. He points out that happiness 0.001 might not be that bad. People seem to avoid suicide out of stubbornness or moral objections, so “the lowest threshold at which living is still slightly better than dying” doesn’t necessarily mean the level of depression we associate with most real-world suicides. It could still be a sort of okay life. Derek Parfit describes it as “listening to Muzak and eating potatoes”. He writes:
my pillow

my pillow is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 05, 2021 and March 05, 2021. The archive places it in contexts such as "there is a world of difference between the my pillow guy and Henry Kravis". It most often appears alongside A Real Dog, Americans, Astors.

Reference entry
my pillow
Mention count
1
Issue count
1
First seen
March 05, 2021
Last seen
March 05, 2021
March 05, 2021 · Original source
Upper class here, which is definitely middle class to say but I think it's ok since I'm anonymous. I would say that the one big change to the class system he outlined is that new money can definitely buy its way to the upper class. This was unthinkable for centuries but in the money obsessed current age is quite doable. Of course there is a world of difference between the my pillow guy and Henry Kravis so it's far from axiomatic that great wealth equals great class prestige. But where you used to see museum, presitigious university and music hall boards stuffed with Cabots and Astors those seats have been completely occupied by billionaires with maybe one or two exceptions for old times' sake. Get on a couple of those and you have risen to the top of the class hierarchy.
Mylar

Mylar is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2025 and October 24, 2025. The archive places it in contexts such as "a vision-protecting Mylar solar filter". It most often appears alongside A Ordem, Abraham Lincoln, ACX.

Reference entry
Mylar
Mention count
1
Issue count
1
First seen
October 24, 2025
Last seen
October 24, 2025
October 24, 2025 · Original source
But if He does try to trick people, He should succeed. I can’t say either of these two things with confidence. Doesn’t the Biblical God sort of try to trick Abraham into thinking he’s going to have to sacrifice his son? And what is God, anyway? Isn’t the whole world a product of God? Does the existence of mirages in the desert count as “God trying to trick people”? Does that fact that we know there are mirages imply that God failed? Still, Ethan’s take on the “sun” miracle of Fatima seems like an unusually clear-cut case of God trying to trick people and failing, and I’m uncomfortable with it. You can always add more overfitting. God’s goal was for the crowds at Fatima to be fooled, but then for Dalleur (2021) to figure it out, and so He achieved His goal perfectly. Okay. But speaking of overfitting… If I understand Ethan right, Fatima was an objective omnidirectional light show, plus a unidirectional heat ray. Ghiaie was a spotlight-shaped unidirectional lightshow. Benin City was a subjective omnidirectional light show limited to a single field, plus an objective unidirectional heat ray. God implemented all of these miracles in completely different ways. Why? Inscrutable God reasons. This isn’t a terrible answer. People often do things for reasons I can’t explain - if I could predict Trump’s behavior, my stock market returns would be much higher. And surely God, as a being with motives and knowledge far beyond my ken, should be even more incomprehensible. But there was an interesting recent Notes debate about a Bentham Bulldog’s post. BB said that atheists had many problems - how was the world created? how do you overcome skepticism? what happened at Fatima? - whereas theism only has one problem - the problem of evil. Evil is a big problem, but it’s at least nice to only have one. Some of the commenters - and I can no longer find the comment I liked anymore, but don’t take this as an original insight from me - pointed out that this is cheap. If you are an atheist, you need to answer many how questions. How did the miracle at Fatima happen? If you try to explain it with natural laws - for example, gravity - it’s fair for an interlocutor to point out that gravity can’t do that; it can only make things fall. If you’re a theist, you have a free option to convert any how question to a why question. How? Because God did it! Your interlocutor can’t object, because we know God can do anything. But in exchange, you now have a why question - why did God do that, and not something else? The sum of all why question - the fact that the real world doesn’t look like it was optimized for some specific plausible motive like goodness - is the problem of evil. Thus, it is exactly equivalent to all the inconvenient “how” questions you hoped you’d avoided. The commenter sarcastically compared this to an attempt to sweep all scientific anomalies under the rug as “the problem of uncharacteristicness”. How did Fatima happen? “Well, it must have been produced by laws of physics, so there!” But the sun spinning and dancing through the sky is hardly what you would expect from the laws of physics. “Yeah, whatever, that’s just the ‘problem of uncharacteristicness’, we’ve already priced that one in, at least we only have one problem!” This made me more attuned to questions of God’s motives. Yeah, it is kind of weird that God would create the same miracle three different ways, and we don’t know why. Yeah, it is kind of weird that God would try to trick people into thinking a non-sun-object was the sun, then let a few smart people working years later see through the deception. Are these problems of motive exactly as problematic for the theist as 70,000 people seeing the sun do impossible things is for the atheist? My gut answer is no. Should I trust my gut? Dylan: In Defense Of Evan Harkness-Murphy Evan wrote the original response to Ethan, before I got involved in the debate. I was a bit harsh on him, saying that his part about the child-seers was fine, but calling his investigation of the sun miracle superficial and unfairly dismissive. Dylan of Chaotic Neutral writes In Defense Of Evan Harkness-Murphy, and Evan additionally defends himself here. Before getting to Dylan’s post - yeah, I was unfair to Evan (partly this is because my brain has trouble remembering that Ethan Muse and Evan Murphy are two different people). In particular, I described his hypothesis on the child-seers as being that they “confabulated” their visions, a term that Evan took great pains to disclaim in his actual post. I was thinking of a broader definition of “confabulation” that includes hallucination-like phenomena - but Evan was right that if I had read his post carefully, I wouldn’t have used the specific word he said he was against. I mostly just skimmed it to see if he had a really good explanation for the sun miracle thing, then got annoyed when he didn’t. But Dylan has additional complaints. He writes: Evan DID give this miracle the attention it deserved. He spent 18 hours researching and writing his article, presenting much of the same evidence and coming to many of the same conclusions that Scott did, and he did it as an ordinary citizen with a “day job” and in a household that “does not possess a dishwashing machine.” What more could you ask of a skeptical individual!? Unlike myself and the other lazy skeptics, he actually did respect this miracle claim enough to do a proper investigation. And towards the end, yes, he decided to wrap up early […] To criticize Evan’s conduct here in this miracle debate is to set an extremely high bar that cannot possibly be met by the overwhelming majority of the skeptical community. Such exacting standards will ultimately only serve to discourage diligent skepticism like Evan’s and incentivize lazy skepticism like mine. I have two partial defenses of my own actions. First, I think the majority of those 18 hours were spent on the child-seer section, which I acknowledged was good. I didn’t care about that part. To me, the trouble of explaining how three children can say in a convincing and honest-sounding and semiconsistent way that they saw the Virgin Mary is a rounding error compared to the trouble of explaining how 70,000 people can say in a convincing and honest-sounding and semiconsistent way that they saw the sun fall from the sky. But second, I think Dylan is arguing that Evan should get an A for effort. I agree. He put in a lot of work, he adhered to good scholarly principles, and he hit all of the beats that a skeptical explanation is supposed to hit. The only thing he didn’t do, from my perspective, is defuse the fact that the Fatima miracle is extremely creepy, and I have no idea what to do with it, and I can’t fit it into my ontology. Evan’s only attempt to defuse the miracle was that it was a hallucination or illusion or something. This is a reasonable conjecture, but for me it was already priced in - as soon as you hear about a miracle, the obvious next step is “well, maybe it was a hallucination or illusion or something”. I didn’t feel like his piece added anything extra. Generously, some of his tangential points - like that Garrett and Almeida weren’t the perfect skeptics they are sometimes portrayed as - might have defused 1% of my discomfort. I think a reasonable conclusion for this would have been “I’ve rehearsed the obvious arguments for why it is possible to be skeptical of anything, I’ve found some tangential facts that maybe remove 1% of the mystery, but man, I don’t know, this really needs lots more investigation”. My research hardly provided any kind of brilliant omni-solution, but I think that learning about the Ghiaie/Benin/Lubbock/Medjugorge followup miracles and the Redditor testimonies each defused about 15% of my reluctance to accept Fatima as natural, and the fire kasina + Khomeini stuff defused another 10%, to the point where I’m only about 60% as confused and unhappy as when I started. I hope I correctly signposted this level of success/failure to the reader. On Miracles Other responses tried to assert a general point that we should always disbelieve miracles. I. Eugene Earnshaw writes that We Do Not Need To Care About Miracles. If I understand his argument right: there are many examples of anomalous phenomena (eg crop circles) and stage magic (eg sawing a woman in half). When we don’t know how these are done, they seem impossible, and (almost) no amount of armchair reasoning can produce a plausible explanation. But in many cases, we have eventually figured them out - some “white hat” crop circlers explain how they make their seemingly-impossible patterns, and some magicians publish explanations of their tricks. After the fact, we can see how these seemingly-impossible things followed natural law after all. So we shouldn’t worry too much each time we encounter a new miracle that hasn’t yet been explained. Okay, but - suppose that the Pope said “I’m tired of convincing you people the normal ways, I’m going to start blowing up mountains”, and pointed his papal staff at Mt. Everest, and it exploded. And then we asked him to repeat the performance, and he did so as many times as we asked him, again and again. Would we shrug and say “Nothing to see here, I’m sure there’s some reasonable explanation”? If the miracle were sufficiently convincing, we would either believe it, or at least think it pointed at something interesting (maybe the Vatican obtained super-nukes and is hiding them under mountains and choreographing their detonations - but this would be pretty important and very different from “nothing to see here”). Ben Landau-Taylor gives a related answer, reminding us that meteorites used to be dismissed on exactly these grounds. The science of the day didn’t allow for non-planet objects to be in space, so rocks falling from the sky was every bit as weird as the sun dancing and changing colors. “When President Jefferson was told that Professors Silliman and Kingsley had described a fall of stones from the sky at Weston, in Connecticut, he remarked: ‘It is easier to believe that two Yankee professors will lie than to believe that stones will fall from heaven.’” In the end, I think we just get back to regular Bayesianism. We have two hypotheses: First, that the world acts entirely according to natural law. Second, that sometimes it includes divine intervention (or very surprising natural laws that we wouldn’t have predicted beforehand). We start with a high prior on the first hypothesis based on our long history of seeing only natural events. When we see evidence that is more likely on the second hypothesis than the first, we update in favor of it. We should remember that “more likely on the second hypothesis than the first” is full of pitfalls - on the first hypothesis, it’s likely that there will be many skilled fraudsters and stage magicians, so even very strange-seeming anomalies might not be very unlikely under it. Still, at the point where the Pope starts blowing up mountains, maybe you think it’s pretty unlikely that stage magic could accomplish this, and you update a little. II. Omne Bonum makes a different point: there are many possible miracles. Most do not occur. Yes, a few of them do. But can we be sure it’s above the background rate? Even if there are no true miracles, you’ll get one-in-a-million coincidences one-millionth of the time. If you’re not good at accounting for the 999,999 failures - and people aren’t - this will look impressive. Against this, what is the base rate for the sun changing color and dropping out of the sky, at the precise time that child-seers prophecied a miracle would occur? Seems lower than one in a million. Impossible things should never happen. Something as simple as my pen vanishing from my desk, in plain sight, while I am looking straight at it, should completely demolish all of my priors against miracles and make me near-certain that something beyond normal physical law is going on - or that I’m crazy, or dreaming, or something other than just “well it was a coincidence”. III. FLWAB takes on Hume’s argument against miracles (see also Kenny Easwaran here), which - sorry, I realize it’s suspicious to say this about a famous philosopher - is extremely bad. Hume argues that a miracle is a violation of natural law. And a natural law is something that is always true. But since it’s always true, it can’t be violated. And if we eventually confirmed that it was violated, then we were wrong about it being a natural law. Which means its violation wasn’t even a real miracle anyway. This seems to be a purely semantic argument. We know that the Red Sea usually stays in one place. But suppose Moses lifts his staff and parts the Red Sea, and that all of this is very convincing (we witness it personally, we measure the sea with various instruments, etc). I think Hume would have to say that we have disproven the natural law “the Red Sea usually stays in one place” - but only in favor of a new natural law “the Red Sea stays in one place except when Moses raises his staff”. And since we have never observed a violation of this new natural law, no miracle has occurred! Against this, we can call the way things work 99.999% of the time, when God isn’t acting directly, and when everything is proceeding via predictable material patterns “natural law”, and the very rare deviations that only occur in the presence of God or other extremely holy figures “miracles”. If for some reason you hate that terminology, come up with a new word, “shmiracle”, for the abnormal phenomena that only occur secondary to God’s direct intervention, and then we can argue whether shmiracles exist. IV. Why am I insisting on this so hard? This question of miracles is no different from every other question, where confirmation bias is a part of normal Bayesian reasoning. If you believe that vaccines don’t cause autism, then any given study showing that they do is likely to be a fraud or a mistake - especially given the history of such frauds, and the political pressures for producing them. But you gained your belief that vaccines don’t cause autism through some normal amount of evidence, and if the evidence that they did cause it ever become truly overwhelming, you would switch sides. The key skill of rationality is to know when to update your beliefs how much. These arguments feel like sleights-of-hand arguing that you can avoid ever updating on this question. I don’t think Bayesian reasoning provides an excuse for this. I think some of these arguments attempt to make an objection that the prior probability of miracles is zero, and so no matter how much evidence you get, you can never update towards them. But the prior probability of miracles isn’t zero unless either the prior probability of God’s existence is zero, or the probability that God intervenes in the universe is zero. I don’t know any infinitely-convincing argument for either of these points, so I think miracles have a prior probability above zero, which means we have to treat them the same as any other hypothesis. Yes, we will need many extra guardrails and cautions and good heuristics to prevent ourselves from getting bamboozled by the pitfalls that lurk in this area in particular. But that’s true of everything! You also need extra guardrails and cautions and heuristics to prevent yourself from getting bamboozled by scientific studies! There’s no substitute for doing the work. Actual Highlights From The Actual Comments Josh (blog) writes: I’d add that we have at least one verified case where a sun miracle was occuring, and an actual group of fedora wearing atheists were present with a modified telescope, and did not see anything interesting. >> “At the Conyers site, the Georgia Skeptics group set up a telescope outfitted with a vision-protecting Mylar solar filter, and on one occasion I participated in the experiment. Becky Long, president of the organization, stated that more than two hundred people had viewed the sun through one of the solar filters and not a single person saw anything unusual (Long 1992, 3; see figure 1).” https://centerforinquiry.s3.amazonaws.com/wp-content/uploads/sites/29/2009/11/22164423/p14.pdf Funny, but they don’t provide information like whether people were seeing sun miracles at the exact moment the telescope was being used, or whether anyone who could see a sun miracle without the telescope switched to using the telescope and then it stopped. They just say they brought a telescope to a Marian site where some people had seen sun miracles at some point. Even if they clarified that some people had used the telescope while seeing a sun miracle and had it immediately stop miracle-ing, I don’t think this would update me very much. We know it’s not the real sun (Ethan says fake sun, I say subjective phenomenon), and we know the non-Fatima miracles aren’t objective (Ethan says only Fatima was objective, I say none of them were objective). John Schilling writes: Twenty-nine *thousand* words on this subject, and none of them are “unidentified”, “flying”, or “object”. Well, OK, there are a few uses of that last, but in the strained phrasing of “UFO-like object”, as if we are preemptively discounting the possibility that sun miracles are actually UFOs. Sun miracles are actually UFOs, full stop. Not “flying saucers”, not “alien spaceships”, maybe “divine miracles”, but definitely “unidentified flying objects”. We invented that last phrase for a reason, and this is exactly that reason. Which means, the thing I learned from this is that the younglings have completely forgotten all that was learned in the Before Times about UFOs. And that, in this context, Scott is a youngling - UFOs seem to have faded from pop culture in the 1990s. Thanks for making me feel old, Scott :-) With the benefit of age and experience, I read the first few paragraphs, made the tentative conclusion that this was almost certainly [see section 6], but figured Scott wouldn’t be doing this deep a dive if it was that simple. And here we are. It probably is just that simple, and now we can back that up with a fairly exhaustive look at the alternatives. For which, unironically, thank you Scott. It’s good to sometimes double-, triple-, and quadruple-check the obvious conclusion. But for those of us who grew up in the 1980s, who were “rationalists” when rationalism hadn’t been invented and we had to call ourselves “skeptics”, UFOs were as important a subject of rationalist/skeptical inquiry as is AI risk today (and for about the same reason). People learned an awful lot in those days. One of those things is that most people don’t spend much time really looking at the sky and will consistently fail to recognize even slightly-unusual phenomena, like the sun partially veiled by clouds. And the other, more important thing is that when presented with an image they don’t recognize, people will very predictably see what their culture has taught them to expect to see. In 1880s-1890s America, any weird thing in the sky was clearly a fantastic airship, built by some mad scientist out of a Jules Verne novel, and was perceived with a wealth of surrounding detail all aligned with that model. 1950s-1980s America, the same things were clearly “flying saucers”, fantastic alien spaceships piloted by little green or grey men, with the same level of impossible detail. And anywhere you’ve got ten thousand devout Catholics fervently hoping to see a Miracle involving the Sun, and the weather makes the sun look a bit wonky... For an old-school skeptical experiment at understanding this effect, https://centerforinquiry.s3.amazonaws.com/wp-content/uploads/sites/29/1980/04/22165441/p34.pdf TL, DR, a gathering of UFO enthusiasts expecting to see a flying saucer in the night sky, are presented with thirty seconds of a monochromatic point source of light at ground level, stationary and unchanging except for one brief interruption. What is perceived, is an object high in the sky with finite angular size and geometric shape, of multiple colors, and conspicuously moving, all consistent with the pop-culture concept of a flying saucer and not some prankster with a spotlight. I considered discussing the UFO angle (the section heading would have been “Virgin Galactic”), but in the end I couldn’t justify it. Yes, the phenomenon is trivially a UFO (in the sense of a thing in the sky we don’t understand). But does this help us? When I think of UFOs, I think of people arguing about whether something was the planet Venus, or a weather balloon, or aliens. But Fatima obviously wasn’t Venus or a balloon (though, uh, see here for a dissenting take). And if it was aliens, you’d have to explain why they pretended to be the Virgin Mary and discussed a bunch of Catholic inside-baseball with a trio of child-seers for several months. So what’s left? When I asked John, he answered: UFOs, are just people seeing something they don’t understand and trying to interpret it by an overweighted, culturally-transmitted prior. Which differs from culture to culture. And that’s something we know a lot about. Which you seem to have independently rediscovered, but I can’t help thinking you’d have got there a lot faster if you’d had a proper map of the territory. A map which includes no aliens outside of the imaginary sort. Maybe one way to rescue the UFO connection is to say that there’s so much weirdness that we should be less willing to take any given example of weirdness on its own terms. I asked in the comments for other examples of miracles as compelling as Fatima. People suggested some of the better-verified reincarnation accounts, some of the better-verified UFO sightings, and some of the more spectacular psi phenomena. I don’t know if these are all exactly as strong as Fatima, but I think many of them are closer to Fatima than to the traditional skeptical conception of an alcoholic liar asserting with zero evidence that he dun saw dem aliens one night. When viewing all of these anomalies as a gestalt, we can go four different directions: Individualized natural explanations. The UFOs were swamp gas and weather balloons. The reincarnation stories are toddlers who are naturally gifted at cold reading. Fatima was entoptic phenomena. Sea serpents are really big oarfish.
Myspace

Myspace is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 22, 2022 and September 22, 2022. The archive places it in contexts such as "the founders of Friendster and Myspace aren't infamously super-rich". It most often appears alongside Adam Neumann, Alex Roesch, Amazon.

Reference entry
Myspace
Mention count
1
Issue count
1
First seen
September 22, 2022
Last seen
September 22, 2022
September 22, 2022 · Original source
I think this is actually a significant problem w/ Scott's last argument - the founders of Friendster and Myspace aren't infamously super-rich, because unlike Zuck, they were not able to keep their thing going strong, in the face of competition, over a long period of time. Getting in first is a huge advantage - but then competition comes in and challenges you. If you don't rise to that challenge, you may walk away with some I-did-it-first money, but the competition will wind up getting the big pot. If you consistently whoop the competition, it's either because you're providing better value, or because you're shrewder at business (this latter part is something the left can perhaps legit complain about, but it's a hard thing to correct accurately). To the extent you're providing better value than all the other competitors who come along over the years, you should reap proportionate rewards. So it is w/ amazon - no one else has 2 day shipping afaik. This accords w/ a general statement about profit margins and competition - low competition should naturally lead to high profit margins, because you're apparently doing something so hard or risky that hardly anyone else can manage to pull it off (this argument falls apart completely when you have low competition because you're exploiting regulation, e.g. IP laws, or when you have a true monopoly).
Also, I wonder how long the Friendster/MySpace example should stay valid for. If Facebook reigns unchallenged for the next millennium, will people still say “Yes, but once in elden days upon Earth-That-Was there was a site called MySpace which was on top for about two years and then Facebook beat it, so it’s not a natural monopoly! We could still get a replacement at any time!” I’m not claiming I am sure Facebook is a natural monopoly. But surely we should be updating our chance of this a little for each year that goes by without it being replaced. How much?
N95

N95 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 30, 2025 and October 30, 2025. The archive places it in contexts such as "COVID-era masks and N95s". It most often appears alongside 767 AD, @Scientific_Bird, ACX.

Reference entry
N95
Mention count
1
Issue count
1
First seen
October 30, 2025
Last seen
October 30, 2025
October 30, 2025 · Original source
45: Andrew Snyder-Beattie on the latest advances in biodefense. Without having fully resolved the debate over the real-world utility of COVID-era masks and N95s, the next generation of masks - elastomeric respirators - seem significantly more effective, including for people not specially trained in wearing them. Also, propylene glycol vapor - ie the fog in fog machines - kills all germs. Having indoor spaces constantly enveloped in fog is a weird ask, but we might find ways to make it work for crucial infrastructure during a pandemic, and “the US already produces enough to cover all industrial and much residential floorspace.” More things I didn’t know: “In a worst-case scenario where all crops die instantly, the US has enough stockpiled food (including animal feed) to last at least 18 months.”
naltrexone

naltrexone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 13, 2024 and August 13, 2024. The archive places it in contexts such as "naltrexone seems to treat a whole host of different drug and behavioral addictions". It most often appears alongside alcoholism, Alhadeff et al. (2012), alpha-adrenergic receptors.

Reference entry
naltrexone
Mention count
1
Issue count
1
First seen
August 13, 2024
Last seen
August 13, 2024
August 13, 2024 · Original source
Broad-spectrum dampening of the reward system is a terrible fate. Some antipsychotic drugs like haloperidol do this. Take too much haloperidol, and you’ll sit motionless until you die, because no action feels worth it. But the existence of silver bullet anti-addiction medications - Ozempic isn’t the only one, naltrexone seems to treat a whole host of different drug and behavioral addictions - suggests there’s also a sort of narrow-spectrum dampening, one which affects addictions and nothing else.
Naproxen

Naproxen is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2021 and February 05, 2021. The archive places it in contexts such as "You listed three major side effects of this drug... One in a zillion people who use Naproxen ("Aleve") becomes red-green colorblind". It most often appears alongside Adderall, Anthony Fauci, aspirin.

Reference entry
Naproxen
Mention count
1
Issue count
1
First seen
February 05, 2021
Last seen
February 05, 2021
February 05, 2021 · Original source
"You listed three major side effects of this drug, but I got a side effect that isn't on your list. Maybe you should add it in." All drugs have an infinite number of possible side effects. One in a zillion people who use Naproxen ("Aleve") becomes red-green colorblind. Capecitabine ("Xeloda") can sometimes make you lose your fingerprints, which sucks if your computer has biometric security. If listed all side effects of anything, we would be here all day. Still, I get nervous when I get emails like this. What if an interior designer takes Aleve, loses their color vision, and it's my fault for not warning them?
Nardil

Nardil is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 06, 2024 and September 06, 2024. The archive places it in contexts such as "he was put on Nardil, an MAOI"; "The culprit, of course, was Nardil"; "suppression by the Nardil, finally glimpsed its chance to break free". It most often appears alongside #MeToo, 21st century political dogmatism, Advanced Tax.

Reference entry
Nardil
Mention count
1
Issue count
1
First seen
September 06, 2024
Last seen
September 06, 2024
September 06, 2024 · Original source
In his youth, Wallace was beset by mental breakdowns. He dropped out of school multiple times, underwent electroshock therapy, and contemplated suicide. When in grad school, he was put on Nardil, an MAOI. MAOIs work by inhibiting Monoamine Oxidase, which in turn hoovers up monoamine neurotransmitters like serotonin, dopamine and norepinephrine. This double negative leaves the user with a more motivated, peaceful and energized brain chemistry.6
This was the neuropharmacological lot in which Wallace was parked in 1985.7 He remained on Nardil through the writing of Infinite Jest, two collections of essays, two books of short stories, and the rough draft of The Pale King. Through it all, Wallace would’ve been on the Tyramine Diet, avoiding cheese, hot dogs and fermented foods. He was never entirely satisfied with being on antidepressants. In the words of his friend, Jonathan Franzen, he was a “perfectionist” with an “aversion to seeing himself as permanently mentally ill.” He tried going off Nardil in 1988, but fell into a profound depression, and was only able to get Nardil to work again by combining it with electroshock therapy.
By 2007, a decade in, he’d made progress, but the book was still far from any kind of final form, and he felt stuck. In the Spring of that year, he went to a Persian restaurant and was left with severe stomach pains. The culprit, of course, was Nardil.
ND

ND is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "no bacopa is entirely trustworthy, but at least ND and PE are better than Swanson". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
ND
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
Regarding the overages, I agree that it’s better to penalize something more for an underage than an overage, but I am still not sure this is good communication. Consider for example their bacopa rankings. Just looking at this, I would come away with the conclusion “no bacopa is entirely trustworthy, but at least ND and PE are better than Swanson”. But if I’m understanding right, the whole ranking is entirely driven by overages, and nobody (including the brand getting a C-) has any other problem. I suppose it’s fair to, if everything is exactly the same, rank based on a minor issue, but I think if I didn’t understand what was going on here I would be much more concerned about Swanson than justified.
NestFresh

NestFresh is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2025 and July 21, 2025. The archive places it in contexts such as "recently got its first American champion in NestFresh, available at Whole Foods". It most often appears alongside Arizona, Asterisk Magazine, Astralcodexten Com.

Reference entry
NestFresh
Mention count
1
Issue count
1
First seen
July 21, 2025
Last seen
July 21, 2025
July 21, 2025 · Original source
IAA is promoting a technological solution - in ovo sexing - that lets farmers identify eggs by sex and only hatch the female ones. This is already widespread in Europe, but recently got its first American champion in NestFresh, available at Whole Foods in Southern California, Arizona, and Nevada now, and elsewhere later this year. Other companies are watching their performance - so if you support this effort, consider buying NestFresh eggs with the "Humanely Hatched" label. Read more here.
Netflix

Netflix is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "announce himself as a Netflix employee". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Netflix
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Corey's plan was to infiltrate [DVD related online] communities. He wouldn't announce himself as a Netflix employee. Posing as a home theater enthusiast or cinephile, he would join the conversation in communities geared toward DVD fanatics and movie buffs, befriend the major players, and slowly, over time, alert the most respected commenters, moderators, and website owners about this great new site called Netflix. We were months from launch, but he was planting seeds that would pay off...big time.
— That Will Never Work by Marc Randolph (Netflix)
Neuraxpharm

Neuraxpharm is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "gotten money from Neuraxpharm". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
Neuraxpharm
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Newbury-Broxham Goods

Newbury-Broxham Goods is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 01, 2022 and December 01, 2022. The archive places it in contexts such as "a boring factory with a name like Newbury-Broxham Goods". It most often appears alongside Amalgamated Bank, Andover, anti-Semitism.

Reference entry
Newbury-Broxham Goods
Mention count
1
Issue count
1
First seen
December 01, 2022
Last seen
December 01, 2022
December 01, 2022 · Original source
At their worst, they mostly held ultra-expensive parties, drifted into alcoholism, and participated in endless “my money is older than your money” dick-measuring contests. And they were jocks - certainly good at lacrosse and crew, but their kids would be much less likely than modern elites’ to become a scientist, professor, doctor, or lawyer. Not only that, they were boring jocks - they stuck to a few standard rich people hobbies (yachting, horseback riding) and distrusted creativity or (God forbid) quirkiness. Their career choices were limited to the family business (probably a boring factory with a name like Newbury-Broxham Goods), becoming a competent civil service administrator, or other things along those lines.
Nexium

Nexium is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 17, 2021 and November 17, 2021. The archive places it in contexts such as "Like this ACSH article about Nexium". It most often appears alongside ACE-2 receptor, ACSH, Ahmed et al.

Reference entry
Nexium
Mention count
1
Issue count
1
First seen
November 17, 2021
Last seen
November 17, 2021
November 17, 2021 · Original source
Source. Real data would follow something like a bell curve. This is going to require a social norm of always sharing data. Even better, journals should require the raw data before they publish anything, and should make it available on their website. People are going to fight hard against this, partly because it’s annoying and partly because of (imho exaggerated) patient privacy related concerns. Somebody’s going to try make some kind of gated thing where you have to prove you have a PhD and a “legitimate cause” before you can access the data, and that person should be fought tooth and nail (some of the “data detectives” who figured out the ivermectin study didn’t have advanced degrees). I want a world where “I did a study, but I can’t show you the data” should be taken as seriously as “I determined P = NP, but I can’t show you the proof.” The second reason I think this, aside from checking for fraud, is checking for mistakes. I have no proof this was involved in ivermectin in particular. But I’ve been surprised how often it comes up when I talk to scientists. Someone in their field got a shocking result, everyone looked over the study really hard and couldn’t find any methodological problems, there’s no evidence of fraud, so do you accept it? A lot of times instead I hear people say “I assume they made a coding error”. I believe them, because I have made a bunch of stupid errors. Sometimes you make the errors for me - an early draft of this post of mine stated that there was an strong positive effect of assortative mating on autism, but when I double-checked it was entirely due to some idiot who filled out the survey and claimed to have 99999 autistic children. In this very essay, I almost said that a set of ivermectin studies showed a positive result because I was reading the number for whether two lists were correlated rather than whether a paired-samples t-test on the lists was significant. I think lots of studies make these kinds of errors. But even if it’s only 1%, these will make up much more than 1% of published studies, and much more than 1% of important ground-breaking published studies, because correct studies can only prove true things, but false studies can prove arbitrarily interesting hypotheses (did you know there was an increase in the suicide rate on days that Donald Trump tweeted?!?) and those are the ones that will get published and become famous. So if the lesson of the original replication crisis was “read the methodology” and “read the preregistration document”, this year’s lesson is “read the raw data”. Which is a bit more of an ask. Especially since most studies don’t make it available. The Sociological Takeaway I’ve been thinking about this one a lot too. Ivermectin supporters were really wrong. I enjoy the idea of a cosmic joke where ivermectin sort of works in some senses in some areas. But the things people were claiming - that ivermectin has a 100% success rate, that you don’t need to take the vaccine because you can just take ivermectin instead, etc - have been untenable not just since the big negative trials came out this summer, but even by the standards of the early positive trials. Mahmud et al was big and positive and exciting, but it showed that ivermectin patients recovered in about 7 days on average instead of 9. I think the conventional wisdom - that the most extreme ivermectin supporters were mostly gullible rubes who were bamboozled by pseudoscience - was basically accurate. Mainstream medicine has reacted with slogans like “believe Science”. I don’t know if those kinds of slogans ever help, but they’re especially unhelpful here. A quick look at ivermectin supporters shows their problem is they believed Science too much. @jonno_bosch I work in hospitality so I need things to return to normal ASAP. I am using Ivermectin as a prophylactic. Hugely influenced by Carvallo trail and Chala trail which showed huge protection","username":"Bannisterious","name":"Andrew Bannister","profile_image_url":"","date":"Fri Feb 12 16:21:14 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":0,"like_count":0,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> @mtskullcrusher @HereComeTheJud @therealjosexy @joeycadre @PeegeRiley @dcwickedestcity @blaireerskine Read Raad. Or Mahmud. Or ICON study from Florida. Or Mexico City hospitalizations study. Or Niaee. Or...\n\nOr just type \"ivermectin covid\" in Google Scholar and read.","username":"fatlas6","name":"fatlas","profile_image_url":"","date":"Thu Sep 02 21:34:59 +0000 2021","photos":[],"quoted_tweet":{},"reply_count":0,"retweet_count":0,"like_count":1,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM"> They have a very reasonable-sounding belief, which is that if dozens of studies all say a drug works really well, then it probably works really well. When they see dozens of studies saying a drug works really well, and the elites saying “no don’t take it!”, their extremely natural conclusion is that it works really well but the elites are covering it up. Sometimes these people even have a specific theory for why elites are covering up ivermectin, like that pharma companies want you to use more expensive patented drugs instead. This theory is extremely plausible. Pharma companies are always trying to convince people to use expensive patented drugs instead of equally good generic alternatives. Ivermectin believers probably heard about this from the many, many good articles by responsible news outlets, discussing the many, many times pharma companies have tried to trick people into using more expensive patented medications. Like this ACSH article about Nexium. Or my article on esketamine. Given that dozens of studies said a drug worked, and elites continued to deny it worked, and there are well-known times where elites lie about drugs in order to make money, it was an incredibly reasonable inference that this was one of those times. If you have a lot of experience with pharma, you know who lies and who doesn’t, and you know what lies they’re willing to tell and which ones they shrink back from. As far as I know, no reputable scientist has ever come out and said ‘esketamine definitely works better than regular ketamine’. The regulatory system just heavily implied it. I claim that with ivermectin, even the people who don’t usually lie were saying it was ineffective, and they were saying it more directly and decisively than liars usually do. But most people can’t translate Pharma → English fluently enough to know where the space of “things people routinely lie about and nobody worries about it too much” ends. So they incredibly reasonably assume anything could be a lie. And if you don’t know which statements about pharmaceuticals are lies, “the one that has dozens of studies contradicting it” is a pretty good heuristic! If you tell these people to “believe Science”, you will just worsen the problem where they trust dozens of scientific studies done by scientists using the scientific method over the pronouncements of the CDC or whoever. So “believe experts”? That would have been better advice in this case. But the experts have beclowned themselves again and again throughout this pandemic, from the first stirrings of “anyone who worries about coronavirus reaching the US is dog-whistling anti-Chinese racism”, to the Surgeon-General tweeting “Don’t wear a face mask”, to government campaigns focusing entirely on hand-washing (HEPA filters? What are those?) Not only would a recommendation to trust experts be misleading, I don’t even think you could make it work. People would notice how often the experts were wrong, and your public awareness campaign would come to naught. But also: one of the data detectives who exposed some fraudulent ivermectin papers was a medical student, which puts him somewhere between pond scum and hookworms on the Medical Establishment Totem Pole. Some of the people whose studies he helped sink were distinguished Professors of Medicine and heads of Health Institutes. If anyone interprets “trust experts” as “mere medical students must not publicly challenge heads of Health Institutes”, then we’ve accidentally thrown the fundamental principle of science out with the bathwater. But Pierre Kory, spiritual leader of the Ivermectin Jihad, is a distinguished critical care doctor. What heuristic tells us “Medical students should be allowed to publicly challenge heads of Health Institutes” but not “Distinguished critical care doctors should be allowed to publicly challenge the CDC”? Then what about “believe statisticians”? I’ve never heard anyone propose this before, but re-centering the mystique of scientific-expertise in study-analyzers and study-aggregators rather than object-level scientists is…one way you could go, I guess. Statisticians admittedly sort of failed us here: the first several meta-analyses said ivermectin worked. But the statistical process - the idea that studies are raw materials, but it takes skill to turn them into the finished good of scientific knowledge - sort of comes out looking good. If we need to summarize our takeaway in a slogan of exactly two words, one of which is “trust”, you could do worse than this one. (am I secretly suggesting that we make rationality higher status? Maybe, although rationalists did no better here during the early phase of “looks promising so far” than anyone else, and it was researchers digging into the nitty-gritty of the data who really solved this.) Or maybe this is the wrong level on which to think about this. Maybe there isn’t and can’t be a simple heuristic you can teach everyone in school or via a PR campaign which will lead to them having making good health decisions in an adversarial information environment, without having any negative effects anywhere else. But you also don’t want people to make bad health decisions. So what do you do? The Political Takeaway All of this is complicated by the impression many people (including me) have, that ivermectin boosterism and vaccine denialism are closely linked. The ivermectin evidence is complicated. There’s room for doubt. I can maybe see room for doubt on some marginal vaccine-related issues like how seriously to take the occasional reports of myocarditis in teens. But the basic issue - that the vaccine works really well and is incredibly safe for adults - seems beyond question. Yet people keep questioning it. I think it’s important to address ivermectin support on its own terms - as a potentially plausible scientific theory in a debris field of confusing evidence, which should be debated to the usual standards of scientific debate. I’ve tried to do that above. But this picture wouldn’t be complete without acknowledging the overlap with vaccine denial - a segment of people who are completely crazy and wrong and who happen to have fixated on this mildly interesting question as opposed to some other one with even less evidence. I’ve been trying to figure out a model where ivermectin support and vaccine denialism both make visceral sense to me, and here’s what I’ve got: Imagine that in 2025, an alien invasion fleet reaches Earth. But it got hit by a supernova on the way, the spaceships are partly disabled, and they’re only able to conquer some out-of-the-way place - let’s say Australia. There’s a few cycles of conflict and cease-fire, a few cities get nuked, and finally we settle into an uneasy peace. Over the next few years, humanity grudgingly admits the invaders into the world community. They get a seat in the United Nations. We sort of cooperate with them on projects that are important to both sides, like stopping climate change. We still hate them, but only at the level of ordinary international rivalries, like USA/USSR. In 2035, the aliens announce that a quantum memetic plague from the Andromeda Sector has reached Earth. Billions of people will die unless we let them put an immunity-granting cybernetic implant in all humans’ brain. The aliens admit we haven’t always been friends, and honestly they would still like to conquer us someday. But this plague is an ancient enemy of all sentient beings, they dealt with it on their homeworld eons ago, and they want to help us out here. Humans apparently don’t have the ability to detect quantum memetic plagues, but mortality rates for over-65s do seem weirdly high this year, something like 10x worse than a normal flu season. Do you let the aliens put an implant in your brain, or not? If it helps, the aliens look like this. Surely anyone with a brain that size must know what they’re talking about, right? (source) Fine, you don’t have to decide immediately. The brain implants aren’t even ready yet. Some human scientists suggest wearing face masks in the interim. The aliens say no, that will never work, that’s not how you deal with quantum memetic plagues, if you do anything other than wait for the brain implants you’re anti-science idiots who are wasting precious time and will kill millions of people. Human nations try face masks anyway…and they clearly and conspicuously work. The aliens say whatever, we’re still the advanced spacefaring civilization here, maybe it works for humans but that’s not the point, the point is you’ve got to let us put implants in your brains. Some human scientists suggest reopening vital services. The aliens say no, millions will die, this is “mass human sacrifice”, humans apparently must care nothing about their families’ lives. The humans try reopening anyway, and…it goes kind of okay? Maybe the death rate goes up 10% to 20% or so, hard to say? The aliens say whatever, maybe their calculations were off by a few orders of magnitude, the point is, you have to let us put implants in your brain or you’ll all die. Then some human scientists suggest vaccinating against the plague. The aliens say this is idiotic, vaccines originally come from cowpox, even the word “vaccine” comes from Latin vaccus meaning “cow”, are you saying you want cow medicine instead of actual brain implants which alien Science has proven will work? They make lots of cartoons displaying humans who want vaccines as having cow heads, or rolling around in cow poop. Meanwhile, the first few dozen studies show vaccines work great. Many top human leaders, including war heroes from the struggle against the aliens, get vaccines and are seen going out in public, looking healthy and happy. The aliens say that human science is hopelessly flawed because of complicated statistical concepts that inferior life forms like us don’t even have words for. You need to ignore all the studies and meta-analyses showing that vaccines definitely work, and let the aliens give you brain implants instead. So do you let the aliens put an implant in your brain, or not? Obviously you think long and hard before doing this. And obviously this is an extended metaphor for vaccine denialism. So what’s the difference between the metaphor (where you’re presumably anti-implant) and the real world (where you’re presumably pro-vaccine?) For me, it’s a combination of: The aliens are hostile, so I don’t trust them no matter how smart they are
nicotinamide mononucleotide

nicotinamide mononucleotide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 02, 2021 and December 02, 2021. The archive places it in contexts such as "its close cousin nicotanimide mononucleotide aka NMN". It most often appears alongside Alexandre Gueniot, Algernon’s Law, Alzheimers.

Mention count
1
Issue count
1
First seen
December 02, 2021
Last seen
December 02, 2021
December 02, 2021 · Original source
The other pill is nicotinamide riboside aka NR (and its close cousin nicotanimide mononucleotide aka NMN). The reactions catalyzed by sirtuins involve nicotinamides, and the more nicotinamides you have, the more effective sirtuins are. NR and NMN are cheap, simple chemicals you can buy at any supplement store for $20, and Sinclair is pretty convinced they’re a fountain of youth. He says that when his own father started becoming decrepit, he convinced him to take NMN, and over the space of a few months he started becoming energetic and spry again, and is now traveling the world despite being well into his 70s.
nicotinamide riboside

nicotinamide riboside is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 02, 2021 and December 02, 2021. The archive places it in contexts such as "The other pill is nicotinamide riboside aka NR". It most often appears alongside Alexandre Gueniot, Algernon’s Law, Alzheimers.

Reference entry
nicotinamide riboside
Mention count
1
Issue count
1
First seen
December 02, 2021
Last seen
December 02, 2021
December 02, 2021 · Original source
The other pill is nicotinamide riboside aka NR (and its close cousin nicotanimide mononucleotide aka NMN). The reactions catalyzed by sirtuins involve nicotinamides, and the more nicotinamides you have, the more effective sirtuins are. NR and NMN are cheap, simple chemicals you can buy at any supplement store for $20, and Sinclair is pretty convinced they’re a fountain of youth. He says that when his own father started becoming decrepit, he convinced him to take NMN, and over the space of a few months he started becoming energetic and spry again, and is now traveling the world despite being well into his 70s.
nicotine patch

nicotine patch is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 24, 2024 and April 24, 2024. The archive places it in contexts such as "The 1970s didn’t have any good anti-smoking medication - even the nicotine patch wasn’t invented until after this study was finished". It most often appears alongside 2008 America, @agoodmanbacon, Baicker.

Reference entry
nicotine patch
Mention count
1
Issue count
1
First seen
April 24, 2024
Last seen
April 24, 2024
April 24, 2024 · Original source
Blood pressure They found no effect of insurance on any of the questionnaires, and modest positive effects on vision and blood pressure. How surprising is this? It seems moderately surprising that nobody improved on any of the questionnaires. These seem to measure overall health. Maybe they were bad measures? Maybe 10,000 mostly-healthy people over 8 years doesn’t provide enough power to detect health improvements on questionnaires? I’m not sure. It doesn’t seem surprising to me that nobody improved on smoking, weight, or cholesterol. The 1970s didn’t have any good anti-smoking medication - even the nicotine patch wasn’t invented until after this study was finished. Likewise for weight loss - the 1970s were in the unfortunate interregnum between the fall of methamphetamine and the rise of Ozempic. There were some weak cholesterol medications back then - eg nicotinic acid - but they were rarely used, and doctors weren’t even entirely convinced that cholesterol was bad. For all three of these things, the 1970s state of the art was doctors saying “You should try to stop smoking and eat better.” RAND found that the better insurances led to 1-2 more doctor visits per year. I don’t think that 3 visits to a doctor saying “You should try to stop smoking and eat better” vs. 4 visits to that doctor is going to affect very much. It’s also not surprising that vision improved; the good insurances were more likely to cover glasses, and everyone knows that glasses help your vision. Even Robin admits this is a real effect; he just classifies it as more physics than medicine. Blood pressure is more debatable. The 1970s had some okay blood pressure medications, like the beta-blockers, and doctors weren’t afraid to use them. So it seems possible in theory that better medical care could lead to decreased blood pressure. Still, Robin is skeptical. He says that the improvement in blood pressure found during the study was p = 0.03. In a study with 30 measures, one will be positive at 0.03 by coincidence. The version of the study he’s reading has 30 measures (mine has 5 - 10, depending on how you count the questionnaire). On the other hand, this paper looks into the blood pressure result in more detail. It finds that “plan effects on blood pressure” were three times higher for hypertensives for non-hypertensives; that is, unlike statistical flukes (which we would expect to affect everyone equally), the effect was concentrated in the people we would expect doctors to treat. It also finds that plan effects are higher for poor people; unlike statistical flukes (which would affect everyone equally), the effect was concentrated in the people we would expect insurance to help. And it finds pretty convincing intermediating factors: people with good insurance were 20 percentage points more likely to get hypertension treatment, p < 0.001). So I think it’s a stretch to attribute this one to random noise. This is the study authors’ conclusion as well. They calculate the benefit from this blood pressure improvement and find that: If 1,000 fifty-year-old men at elevated risk were enrolled on a free rather than a cost-sharing plan, then we would anticipate that about 11 of them, who would otherwise have died, would be alive five years later. Still, they describe their study as having a negative result, because: ...these mortality reductions, in and of themselves, are not sufficient to justify free care for all adults. I assume they’re working off of some kind of reasonable cost-effectiveness model for government spending here. Still, if I were a fifty year old adult, I might be willing to personally spend a few hundred extra dollars a year to increase my 5-year-survival-rate by 1%. Certainly I don’t think it’s fair to describe this as “RAND proves medicine doesn’t work.” Robin has a book with more information than I could get from the papers, so I feel bad contradicting him on this one. I’m more confident in my discussion of the next two experiments, which I think are clear enough that we can go back to this one later and apply what we’ve learned. IV. Oregon Health Insurance Experiment In 2008, Oregon had extra money and decided to expand Medicaid, a free insurance program for poor people. Many people applied for the free insurance, the state ran out of money, and they distributed the available Medicaid slots by lottery. This made the expansion a perfect setup for a randomized controlled trial on whether government-provided free insurance helps the poor. Scientists monitored the recipients for two years (why not longer? I think at some point the insurance coverage stopped) and found that the people with Medicaid did in fact use more medical care than the control group. For example, only 69% of the control group described themselves as getting all the medical care they needed, but 93% of the group with insurance did. People with the insurance used more of almost all categories of medication: People who got the free insurance had less medical debt at the end of the study period. They described themselves on questionnaires as having better health (55% vs. 68% at least “good”, p < 0.0001), and were more likely to say their health had improved over the past few months (71% vs. 83%, p < 0.001). They described having better mental health and less depression (25% vs. 33% depressed, p = 0.001). However, Robin notes that many of these subjective changes happened immediately, ie before they even had a chance to use their new insurance. This means they’re more likely to represent mood affiliation (eg “I have insurance now, so I’m optimistic about my health!”). There was no difference on objective health measures, including blood pressure, cholesterol, and HbA1c (a measure of blood sugar / diabetes control). Why not? The authors do the math on diabetes. If you look at the graph above, you see that about 12.5% of controls vs. 17.5% of experimentals took diabetes medications, p < 0.05. Studies find that diabetes medications decrease HbA1c by about one percentage point (normal HbA1c is about 5%, so this is a lot). If 5% of the insurance group took diabetes medications and decreased their HbA1c by 1 pp each, then the HbA1c of the experimental group would decline by 0.05 pp compared to the control group. Their 95% confidence interval of the difference was (-0.1, +0.1 pp), which includes the predicted value. So when they say “insurance didn’t significantly change HbA1c”, what they mean is “the change in HbA1c is completely consistent with the consensus effect of antidiabetic medications”. Could the same be true of the other results, like hypertension? We find that the experimental group was 1.8 percentage points more likely to get a hypertension diagnosis, 0.7 percentage points more likely to get hypertension medications, and had 0.8 points lower blood pressure - but that all of these numbers were nonsignificant. If we take the nonsignificant numbers seriously, 0.7 pp taking antihypertensives caused an 0.8 point blood pressure drop in the full sample, meaning that antihypertensives caused a 100 point blood pressure drop in each user. This definitely isn’t true - a 100 point blood pressure drop kills you - but it means that a plausible pro-medicine result like antihypertensives lowering blood pressure 10 point is well within the study’s confidence interval. Maybe the anti-medicine position is that, for some reason, good insurance doesn’t lead to hypertension diagnosis or antihypertensive medication use? If I understand these numbers right, about 22% of Americans have blood pressure > 140/90, the level at which doctors recommend medication. I expect the marginally-insured poor people in this experiment to be less healthy than average, so let’s say 25 - 30%. In the experiment, about 13.9% of the control group and 14.6% of the experimental group got antihypertension medication. Why so low? This study found that only about 60% of participants in the Oregon study who got the insurance even went to the doctor for non-emergency reasons! Subtract out the ones who refused to take antihypertensives, or who have too many side effects, or whose doctors let this fall through the cracks, and I think the 13 - 15% numbers make sense. This study found that insurance increased hypertension medication use by a central estimate of 0.7 pp, not significant, confidence interval -4.5 to 5.8. Let’s take a convenient central estimate of our likely hypertension rate and say that 28% of our population should have gotten hypertension meds. That means the central estimate increased the percent of people who got recommended hypertension meds from 50% to 53%, and the 95% confidence interval includes up to 71%. So my assessment of the blood pressure results from this study is: At the beginning of the study, about 50% of people who should have been on hypertension meds were. The study had too low power to really figure out how this changed, but the central estimate is +3%, and the 95% CI rules out improvements beyond +21%
nicotinic acid

nicotinic acid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 24, 2024 and April 24, 2024. The archive places it in contexts such as "There were some weak cholesterol medications back then - eg nicotinic acid"; "weak cholesterol medications back then - eg nicotinic acid". It most often appears alongside 2008 America, @agoodmanbacon, Baicker.

Reference entry
nicotinic acid
Mention count
1
Issue count
1
First seen
April 24, 2024
Last seen
April 24, 2024
April 24, 2024 · Original source
Blood pressure They found no effect of insurance on any of the questionnaires, and modest positive effects on vision and blood pressure. How surprising is this? It seems moderately surprising that nobody improved on any of the questionnaires. These seem to measure overall health. Maybe they were bad measures? Maybe 10,000 mostly-healthy people over 8 years doesn’t provide enough power to detect health improvements on questionnaires? I’m not sure. It doesn’t seem surprising to me that nobody improved on smoking, weight, or cholesterol. The 1970s didn’t have any good anti-smoking medication - even the nicotine patch wasn’t invented until after this study was finished. Likewise for weight loss - the 1970s were in the unfortunate interregnum between the fall of methamphetamine and the rise of Ozempic. There were some weak cholesterol medications back then - eg nicotinic acid - but they were rarely used, and doctors weren’t even entirely convinced that cholesterol was bad. For all three of these things, the 1970s state of the art was doctors saying “You should try to stop smoking and eat better.” RAND found that the better insurances led to 1-2 more doctor visits per year. I don’t think that 3 visits to a doctor saying “You should try to stop smoking and eat better” vs. 4 visits to that doctor is going to affect very much. It’s also not surprising that vision improved; the good insurances were more likely to cover glasses, and everyone knows that glasses help your vision. Even Robin admits this is a real effect; he just classifies it as more physics than medicine. Blood pressure is more debatable. The 1970s had some okay blood pressure medications, like the beta-blockers, and doctors weren’t afraid to use them. So it seems possible in theory that better medical care could lead to decreased blood pressure. Still, Robin is skeptical. He says that the improvement in blood pressure found during the study was p = 0.03. In a study with 30 measures, one will be positive at 0.03 by coincidence. The version of the study he’s reading has 30 measures (mine has 5 - 10, depending on how you count the questionnaire). On the other hand, this paper looks into the blood pressure result in more detail. It finds that “plan effects on blood pressure” were three times higher for hypertensives for non-hypertensives; that is, unlike statistical flukes (which we would expect to affect everyone equally), the effect was concentrated in the people we would expect doctors to treat. It also finds that plan effects are higher for poor people; unlike statistical flukes (which would affect everyone equally), the effect was concentrated in the people we would expect insurance to help. And it finds pretty convincing intermediating factors: people with good insurance were 20 percentage points more likely to get hypertension treatment, p < 0.001). So I think it’s a stretch to attribute this one to random noise. This is the study authors’ conclusion as well. They calculate the benefit from this blood pressure improvement and find that: If 1,000 fifty-year-old men at elevated risk were enrolled on a free rather than a cost-sharing plan, then we would anticipate that about 11 of them, who would otherwise have died, would be alive five years later. Still, they describe their study as having a negative result, because: ...these mortality reductions, in and of themselves, are not sufficient to justify free care for all adults. I assume they’re working off of some kind of reasonable cost-effectiveness model for government spending here. Still, if I were a fifty year old adult, I might be willing to personally spend a few hundred extra dollars a year to increase my 5-year-survival-rate by 1%. Certainly I don’t think it’s fair to describe this as “RAND proves medicine doesn’t work.” Robin has a book with more information than I could get from the papers, so I feel bad contradicting him on this one. I’m more confident in my discussion of the next two experiments, which I think are clear enough that we can go back to this one later and apply what we’ve learned. IV. Oregon Health Insurance Experiment In 2008, Oregon had extra money and decided to expand Medicaid, a free insurance program for poor people. Many people applied for the free insurance, the state ran out of money, and they distributed the available Medicaid slots by lottery. This made the expansion a perfect setup for a randomized controlled trial on whether government-provided free insurance helps the poor. Scientists monitored the recipients for two years (why not longer? I think at some point the insurance coverage stopped) and found that the people with Medicaid did in fact use more medical care than the control group. For example, only 69% of the control group described themselves as getting all the medical care they needed, but 93% of the group with insurance did. People with the insurance used more of almost all categories of medication: People who got the free insurance had less medical debt at the end of the study period. They described themselves on questionnaires as having better health (55% vs. 68% at least “good”, p < 0.0001), and were more likely to say their health had improved over the past few months (71% vs. 83%, p < 0.001). They described having better mental health and less depression (25% vs. 33% depressed, p = 0.001). However, Robin notes that many of these subjective changes happened immediately, ie before they even had a chance to use their new insurance. This means they’re more likely to represent mood affiliation (eg “I have insurance now, so I’m optimistic about my health!”). There was no difference on objective health measures, including blood pressure, cholesterol, and HbA1c (a measure of blood sugar / diabetes control). Why not? The authors do the math on diabetes. If you look at the graph above, you see that about 12.5% of controls vs. 17.5% of experimentals took diabetes medications, p < 0.05. Studies find that diabetes medications decrease HbA1c by about one percentage point (normal HbA1c is about 5%, so this is a lot). If 5% of the insurance group took diabetes medications and decreased their HbA1c by 1 pp each, then the HbA1c of the experimental group would decline by 0.05 pp compared to the control group. Their 95% confidence interval of the difference was (-0.1, +0.1 pp), which includes the predicted value. So when they say “insurance didn’t significantly change HbA1c”, what they mean is “the change in HbA1c is completely consistent with the consensus effect of antidiabetic medications”. Could the same be true of the other results, like hypertension? We find that the experimental group was 1.8 percentage points more likely to get a hypertension diagnosis, 0.7 percentage points more likely to get hypertension medications, and had 0.8 points lower blood pressure - but that all of these numbers were nonsignificant. If we take the nonsignificant numbers seriously, 0.7 pp taking antihypertensives caused an 0.8 point blood pressure drop in the full sample, meaning that antihypertensives caused a 100 point blood pressure drop in each user. This definitely isn’t true - a 100 point blood pressure drop kills you - but it means that a plausible pro-medicine result like antihypertensives lowering blood pressure 10 point is well within the study’s confidence interval. Maybe the anti-medicine position is that, for some reason, good insurance doesn’t lead to hypertension diagnosis or antihypertensive medication use? If I understand these numbers right, about 22% of Americans have blood pressure > 140/90, the level at which doctors recommend medication. I expect the marginally-insured poor people in this experiment to be less healthy than average, so let’s say 25 - 30%. In the experiment, about 13.9% of the control group and 14.6% of the experimental group got antihypertension medication. Why so low? This study found that only about 60% of participants in the Oregon study who got the insurance even went to the doctor for non-emergency reasons! Subtract out the ones who refused to take antihypertensives, or who have too many side effects, or whose doctors let this fall through the cracks, and I think the 13 - 15% numbers make sense. This study found that insurance increased hypertension medication use by a central estimate of 0.7 pp, not significant, confidence interval -4.5 to 5.8. Let’s take a convenient central estimate of our likely hypertension rate and say that 28% of our population should have gotten hypertension meds. That means the central estimate increased the percent of people who got recommended hypertension meds from 50% to 53%, and the 95% confidence interval includes up to 71%. So my assessment of the blood pressure results from this study is: At the beginning of the study, about 50% of people who should have been on hypertension meds were. The study had too low power to really figure out how this changed, but the central estimate is +3%, and the 95% CI rules out improvements beyond +21%
nitazoxanide

nitazoxanide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 01, 2023 and February 01, 2023. The archive places it in contexts such as "The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin". It most often appears alongside 2006 Ioannidis paper, ACTIV-6, Alexandros.

Reference entry
nitazoxanide
Mention count
1
Issue count
1
First seen
February 01, 2023
Last seen
February 01, 2023
February 01, 2023 · Original source
Gideon (correctly) phrased this as a non-sinister albeit potentially weird misstep by the study authors, but in trying to summarize Gideon, I (incorrectly) phrased it as a sinister attempt to inflate results. After looking into it, I think Alexandros is completely right and I was completely wrong. Although I sometimes get details wrong, this one was especially disappointing because I incorrectly tarnished the reputation of Biber et al and implicitly accused them of bad scientific practices, which they were not doing. I believed I was relaying an accusation by Gideon (who I trust), but I was wrong and he was not accusing them of that. I apologize to Biber et al, my readers, and everyone else involved in this. My only reservation is that I don’t want to say too strongly that Gideon’s critique is wrong: I haven’t looked through the study documents enough to say with certainty that Alexandros’ reanalysis of the protocol issues is correct (though the superficial check I’ve done looks that way). But my mistakes are completely separate from anything Gideon did and definitely real and egregious. Cadegiani et al (Alexandros 50% right) Flavio Cadegiani did several studies on ivermectin in Brazil; I edited this section in response to criticism by Marinos and others, but the earliest version I can find on archive.is (I can’t guarantee it was the first I wrote) said: A crazy person decided to put his patients on every weird medication he could think of, and 585 subjects ended up on a combination of ivermectin, hydroxychloroquine, azithromycin, and nitazoxanide, with dutasteride and spironolactone "optionally offered" and vitamin D, vitamin C, zinc, apixaban, rivaraxoban, enoxaparin, and glucocorticoids "added according to clinical judgment". There was no control group, but the author helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group based on “a precise estimative based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies”. Patients in the experimental group were twice as likely to recover (p < 0.0001), had negative PCR after 14 vs. 21 days, and had 0 vs. 27 hospitalizations. Speaking of low p-values, some people did fraud-detection tests on another of Cadegiani’s COVID-19 studies and got values like p < 8.24E-11 in favor of it being fraudulent. Also in Cadegiani news: he apparently has the record for completing one of the fastest PhDs in Brazilian history (7 months), he was involved in a weird scandal where the Brazilian government tried to create a COVID recommendation app but it just recommended ivermectin to everybody regardless of what input it got, and he describes himself as: …the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field. And, uh, he’s also studied whether ultra-high-dose antiandrogens treated COVID, and found that they did, cutting mortality by 92% . Which sounds great, except that it looks like most of this is that the control group had a shockingly high mortality rate, much higher than makes sense even in the context of severe COVID. I think the charitable explanation here is that he made this data up too. But the Brazilian Parliament seems to be going with an uncharitable explanation, seeing as they have recommended that Cadegiani be charged with crimes against humanity. Anyway, let’s not base anything important on the results of this study. You can find Alexandros’ full critique here, but again I’ll try to summarize it as best I can. Alexandros is unhappy with my portrayal of Cadegiani’s background. I cite details that make him look strange and maybe fake, but there are other details that make him seem more impressive, like that he won gold medals at a Brazilian Scientific Olympiad.
Carvallo said that zero people in the treatment group of his study got COVID, compared to 58% of people in the control group. This is a pretty implausibly big effect, even by the standards of other pro-ivermectin studies, although I don’t know if anyone else tried the exact same preventative protocol as Carvallo. I think this is a more nuanced story than Alexandros’ version where Buzzfeed just doesn’t know that sometimes studies happen at more than one hospital. Is fraud the best explanation? I think Alexandros thinks of Carvallo as just not keeping very good records, so he doesn’t have raw data, and probably mixed up his numbers a few times or gave false numbers, and didn’t have anything to send his collaborators when they asked. I think this is maybe possible, although it seems suspicious that he falsely said Dr. Lombardo was involved, falsely claimed the hospital involved was doing a different trial, and got very implausible results. I can imagine weird chains of events that would cause all of these things through honest misunderstandings. But they don’t seem like the best explanation. After discussing this with Alexandros, he objects to my use of the term “known fraudster”. Perhaps I should have said “highly credibly suspected fraudster” instead, although in a Bayesian sense nothing can ever be 100% and at some point plausibility shades imperceptibly into knowledge. Still, I feel like my description here was more accurate than Alexandros’, which just mentions the hospital approval issue and says nothing about any of the rest of this in a thousand word subsection about this study in particular. I did err in saying the Carvallo paper was retracted. According to the article: After BuzzFeed News raised questions about how the study’s data was collected and analyzed, a representative from the Journal of Biomedical Research and Clinical Investigation, which published the results, said late Monday, “We will remove the paper temporarily.” A link was removed from the table of contents — but was reinstated by Thursday. The journal’s explanation, provided after this story was published, was that the author “informed us that he has already provided the evidence of his study to the media.” I apologize for the error. Elalfy et al (still disagree with Alexandros) I described this as: As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable […] There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. In the summary post, Alexandros’ entire criticism of my coverage of this trial, one of the seven trials he focuses on as most unfairly covered and uses as the lynchpin of his argument that I am morally culpable for disastrously bad reporting, is: [Elalfy et al] are accused of incompetence for failing to randomize their groups multiple times in Scott’s piece. The paper writes in six separate places that it is not reporting on a randomized trial, amongst them on a diagram that Scott included in his own essay. Hard to imagine how else they could have made it clear. In his full post on this, he goes line by line to point out all the places they say they are non-randomized, pausing to snark about how dumb I am for not noticing each time4. But he never addresses the actual source of my confusion, which is the part of the paper where it says that: Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment. If this was done as described, it should be an (almost) random trial; patients who come in on Wednesdays shouldn’t systematically differ from patients who come in on Thursdays5. But in fact, it looks (assuming I am understanding a very ambiguous table correctly) like there are very large pre-existing differences between the groups, sufficient to explain the entire result. If they in fact followed their days-of-the-week protocol, and it was random as expected, then I’m misunderstanding the table seeming to show very large differences, and they have indeed found evidence for ivermectin’s efficacy. If they didn’t follow their day-of-the-week protocol and it’s non-random, then maybe I’m understanding the table correctly and their groups had large differences to begin with and the fact that they had large differences at the end of the trial doesn’t demonstrate anything about ivermectin. This is all I was trying to say in the post, and instead of having any opinion on it Alexandros just makes fun of me for saying it. I think our actual crux is that Alexandros thinks a table of big differences between the groups has to be post-treatment (based on how big the differences are), whereas I’m not sure (because it’s unclear in the study, and also because the authors describe what could be a randomization method but also go on and on about how nonrandom they are). This is why I thought it mattered how random it was! Maybe instead of mocking me for this, you can admit it’s an important and relevant question! Ghauri et al (still disagree with Alexandros) I describe this as: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. Alexandros notes that these are three differences between experimental/control groups, out of 33 listed characteristics that could have been different. There is approximately a 23% chance (he calculates) that you could get these differences by chance. He accuses me of failing to do a formal Carlisle test - the usual test you would use to determine whether weird differences between randomized groups are because of fraud - instead eyeballing it and getting it wrong. Here I do want to defend myself: I am not accusing Ghauri et al of fraud. In fact, this would be nonsensical: they admit they are assigning patients nonrandomly. Carlisle tests are usually done to show that something about group assignment is impossible (and therefore fraudulent) in a fair random assignment. But these people aren’t claiming to have done a fair random assignment, so I’m not sure what a Carlisle test would prove. My argument is more like: this is nonrandom, therefore we should expect it to be unfair. It is unnecessary, but helpful, to note an actual apparent unfairness - there’s some evidence they gave the ivermectin to less severe patients (as measured by corticosteroid use). Therefore, we can’t necessarily trust this to be a fair trial (which it was never really claiming to be). In the end I kept Ghauri as an okay study, although GMK didn’t so it ended out trashed in the final analysis anyway. I think my thinking was that I never claimed to be only looking at RCTs, so this non-RCT whose between-group-differences confirmed that it was indeed a non-RCT with all the risk of bias that entails, didn’t necessarily need to be ruled out. Still, I don’t think I was wrong to mention this possibility, and I think Alexandros was wrong to suggest that I needed to do extra tests for this to be fair. Borody et al (still disagree with Alexandros) I described this as: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. Alexandros lists his full concerns here. My summary: Scott is being incredibly disrespectful to the authors, who are in fact a legendary gastroenterologist who invented life-saving h. pylori therapy and a brilliant immunologist who invented a well-regarded bronchitis vaccine (in particular, in describing their control group, I said “this is not how you control group, @#!% you”.
Nomifensine

Nomifensine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 15, 2024 and May 15, 2024. The archive places it in contexts such as "Nomifensine seemed promising but was later found to cause a serious blood disorder". It most often appears alongside @the_megabase, A Pan-Species Welfare State, ACX Grantees.

Reference entry
Nomifensine
Mention count
1
Issue count
1
First seen
May 15, 2024
Last seen
May 15, 2024
May 15, 2024 · Original source
For a philosopher, Pearce is very practical. Sure, he has dozens of essays on why it’s morally correct to end suffering. But he also wants to start the project himself. You can read his analysis of dozens of drugs and how they might contribute to some kind of hypothetical future “make everyone happy all the time” cocktail. Early on, he rejects the obvious choices - heroin, cocaine, SSRIs - for the obvious reasons. By the end, he’s investigating weird drugs that even I - who have kind of made a career knowing about weird drugs - have never heard of. Apimostinel originally looked promising, but failed Phase 3 trials. Nomifensine seemed promising but was later found to cause a serious blood disorder. His most promising lead is LIH383, a chemical which seems to increase the brain’s natural opiate tone, potentially producing the effect of a small dose of opiate without any negative effects or addiction potential. But this is way past his ability to test, and so far he hasn’t been able to interest any pharma companies.
Noopept

Noopept is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 04, 2024 and April 04, 2024. The archive places it in contexts such as "a bunch of cholinergic vaso[dilators/modulators] (think noopept)". It most often appears alongside Aaron Peskin, ACLU, AGI And The Efficient Market Hypothesis.

Reference entry
Noopept
Mention count
1
Issue count
1
First seen
April 04, 2024
Last seen
April 04, 2024
April 04, 2024 · Original source
…targeted NIR interference therapy, short UV during the morning, a lot of inversion-based exercises where I focused on contracting/relaxing neck and face muscles, a few customized breathing exercises (think wim hof), figuring out the correct levels for a bunch of cholinergic vaso[dilators/modulators] (think noopept), massage therapies to reduce tension on the spine, some proprioception-heavy movement practices, a niche tibetan metta meditation series… and about 5 other things that are even harder to compress.
nortriptyline

nortriptyline is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "imipramine, nortriptyline, and clomipramine are all reasonable choices". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
nortriptyline
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Amitriptyline is my preferred tricyclic, a large and sprawling class of older antidepressants. Other people might have different preferred tricyclics; imipramine, nortriptyline, and clomipramine are all reasonable choices in different situations. It can also cause tiredness and weight gain, and has a small risk of heart problems in vulnerable/older people. On the other hand, in Andrea Cipriani’s massive meta-analysis of antidepressant efficacy, it ranked first out of 21 different drugs (my third- tier suggestions weren’t studied, because the researchers were cowards).
Notepad

Notepad is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2023 and June 28, 2023. The archive places it in contexts such as "I have to compose on Notepad and then copy-paste to the Gmail window". It most often appears alongside ACX, AdBlock, Bing.

Reference entry
Notepad
Mention count
1
Issue count
1
First seen
June 28, 2023
Last seen
June 28, 2023
June 28, 2023 · Original source
An unblockable moving status bar that switches every few seconds between different messages about the product! This is what they think the people most obsessed with blocking flashing/changing elements on websites want! This new “show a constantly-moving status bar on screen to tell you when they will change another flashing element” thing has also made it onto the front page of Bing, although luckily you can dismiss it there. I would have expected Google to resist. They haven’t. I can no longer write things on Gmail - I have to compose on Notepad and then copy-paste to the Gmail window - because they’ve made it look like this: It cycles between these every few seconds, irregularly, as long as I keep typing. It baffles me that these companies will spend millions of dollars optimizing every aspect of their user interface, then add one completely unnecessary feature that ensures I will never spend more than the absolute minimum possible amount of time using their product. I know I’m not the only person who hates this, because when I Google it, I find Gmail help forum threads like: How do I get rid of the blinking “Draft Saved” message?
Novavax

Novavax is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 16, 2021 and February 16, 2021. The archive places it in contexts such as "we’ll find that P/M, Novavax, AZ, and J&J all cut deaths". It most often appears alongside AIDS, AZ, B117 strain.

Reference entry
Novavax
Mention count
1
Issue count
1
First seen
February 16, 2021
Last seen
February 16, 2021
February 16, 2021 · Original source
In terms of preventing sympomatic infections, the best current data suggests that the Novavax vaccine is 96% effective against Coronavirus Classic, 86% effective against UK, and 60% effective against South Africa. AstraZeneca is something like 80% effective against Classic, 65% effective against UK, and the South African study was kind of bungled but our best guess is "seems pretty bad". Johnson and Johnson is 66-72%+ effective against Classic and 57% effective against South Africa. Pfizer/Moderna hasn't been tested against South Africa in real life yet, but lab studies suggest slightly decreased efficacy.
Prediction: 55% chance that later, when we have great evidence on this, we’ll find that P/M, Novavax, AZ, and J&J all cut deaths from all extant strains by at least four-fifths.When the fifth wave strikes in late spring/early summer, some of the population (~50%?) will be vaccinated, another part of the population (~25%?) will have had the disease already, and the rest (~25%?) will be completely vulnerable. The new strains will probably cause a limited number of mild cases among the vaccinated/resistant, and a larger number of more severe cases among the vulnerable. Either way, the presence of the larger vaccinated/resistant contingent could potentially make this less severe than previous waves. Also, we may have learned more about treating severe COVID (with eg ivermectin, fluvoxamine), which might further decrease deaths.
Novolog

Novolog is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 27, 2022 and January 27, 2022. The archive places it in contexts such as "Humalog and Novolog are effectively equivalent drugs". It most often appears alongside ACA, Acrolectics, Aetna.

Reference entry
Novolog
Mention count
1
Issue count
1
First seen
January 27, 2022
Last seen
January 27, 2022
January 27, 2022 · Original source
The PBM step generally keeps an administrative cost per prescription plus a % of the cost of branded drugs. These companies are: CVS/Caremark, Express Scripts, OptumRx, Prime Therapeutics and a lot of minors. They negotiate "rebates" with manufacturers. This basically works like this: Humalog and Novolog are effectively equivalent drugs. They cost ~$300/month without insurance. The PBM will say to Lilly "That's a nice humalog you've got there. I'm going to need $150/month as a check back to me or else every patient on my plan gets Novolog unless the doctor fills out 500 pages of paperwork to get Humalog AND the patients pay $200 of the cost." Lilly says "ok fine." According to the PBM lobbying organization, PCMA, most of the rebate money goes back to purchasers, but IMO that just makes the problem worse because it makes purchasers complicit in the game by sending them checks that they use to reduce their premiums instead of reducing the cost of drugs to their plan members.
NOW

NOW is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "NOW has their own in-house lab in Chicago"; "NOW has their own in-house lab, and they have been trying to clean up the standards of the industry"; "I trust Nootropics Depot, Thorne, NOW, and Jarrow". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
NOW
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
[Big supplement corporation] NOW has their own in-house lab in Chicago. That's where they test everything. It's about 3-4 times bigger than our lab. Of course they are much bigger than we are, and have been around much longer. That being said, their milk thistle also failed our testing. It had 56% of the claimed silymarins. Literally everyone's milk thistle that we tested failed. That's because they use the faulty UV-Vis number that overstates the actual silymarins by double. Everyone is claiming 80% silymarins, but it really only has 40-50% when tested properly with HPLC or UPLC. Real 80% and 90% silmarin extracts do exist, but they are much more expensive. Why use those when you can just sell the cheaper 40% and claim 80% like everyone else? That's the problem with this industry. If you are the only one properly labeling your stuff, you look less potent than everyone else that is improperly labeling.
NOW has their own in-house lab, and they have been trying to clean up the standards of the industry for a while. We have had a couple things of theirs fail, but only for content lower than label claim, not fake or impure or anything like that. So while I wouldn't say trust everything from them 100%, NOW is one of the better ones in this industry seemingly trying to make things better. I also have more trust for Thorne than most […] every single brand we have tested so far has had at least one thing fail, save for Thorne. Some of the brands have almost everything fail. Others like Life Extension, Jarrow, and NOW have most things pass with only some failing. It's a crap shoot.
Botanicals are more complicated. Commonly-used botanicals from reputable brands are usually about as trustworthy as vitamins, but there are lots of complications around extraction processes and sometimes you might get 50% more or less than you thought. Less-commonly-used botanicals are less clear; you still will rarely find outright sugar pills, but you may find people bungling the chemistry, not caring too much about exact amounts, or selling mushroom mycelium instead of fruiting body. “Male enhancement” products are their own special class of danger zone, as are anything that’s been featured on The Joe Rogan Experience; you should be extra careful to buy from only the most reputable companies. I trust Nootropics Depot, Thorne, NOW, and Jarrow, in that order, but you’ll want to do your own research and maybe check ConsumerLab for the particular product you’re buying.
NOW Foods

NOW Foods is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "He was going back and forth with the lab director from NOW Foods". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
NOW Foods
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
If you knew the half of the shit that goes on in the background of this industry, you'd be disgusted. My lab director went to the AOAC conference last week. Scientists from most of the analytical labs in the US were there, and many of the quality directors from the bigger brands. My lab director was just openly calling products out that we tested and had failed, and everyone was looking at him like he was breaking decorum. There is an unspoken rule in this industry that you don't call out other brands for quality issues, because you know you have some of your own. It's insane! Everyone knows all the products fail. Everyone knows almost nobody is doing things right. However, the status quo makes too many people too much money to change. He was going back and forth with the lab director from NOW Foods, and they have been doing similar things to us. They have been buying products on Amazon and testing them in their lab. Surprise surprise, tons are failing. However, they can't get Amazon to do anything about it. The unwritten rule there is that they don't want to hear about quality issues. They want to put their fingers in their ears and go la la la la laaaaaa. Truly! You can test this yourself. Write Amazon support asking how to report fake reviews, and they will give you a place to report them. Then ask where you can reports fake or impure product, and they will literally stop talking to you. We have tried. We'd love to just send Amazon our testing results of their top products failing lab testing, but they shut any discussion of it down. There's not much money in admitting you have been selling products that don't meet labels claims, and it is so widespread that fixing it would upend the entire industry, so covering their eyes and ears is their choice. In fact, we have been warned that if we make too many waves, we might be punished instead. They might just shoot the messenger because that is easier.
NVG-291

NVG-291 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 02, 2024 and August 02, 2024. The archive places it in contexts such as "A bioengineered molecule, NVG-291, is injected into the spinal cord". It most often appears alongside Ableism, Acapulco, Alberta.

Reference entry
NVG-291
Mention count
1
Issue count
1
First seen
August 02, 2024
Last seen
August 02, 2024
August 02, 2024 · Original source
(Source) A diagram of the human spine next to a diagram of the human body, indicating which parts of the body are innervated by which vertebrae in the spinal column. The cervical, thoracic, lumbar, and sacral regions of the spine are highlighted in different colors, with the corresponding body regions highlighted in the same colors. Starting at the top, the cervical (neck) vertebrae control the head, neck, arms, and fingers. The thoracic (torso) vertebrae control the entire torso and abdomen. The lumbar (lower back) vertebrae control the hips and front muscles of the legs. The sacral (tailbone) vertebrae control the back muscles of the legs and the groin area. The very last vertebra, S5, innervates the anus and genitals. Clayton is injured quite high up on the torso at the T5 vertebra. Let's consider the ramifications of having everything below the nipples be completely numb and limp. To start off, that means that he has no use of the muscles that hold him upright. Nothing keeps me sitting up—no hip flexors, erector spinae, hamstrings, or abdominal muscles. I am arms-and-a-head on a column of Jell-O. He can't put both arms out in front of him, lest he fall over. He has to continuously prop himself up with one arm while doing anything at arm's length. After only 1.5 years of being paralyzed, this has already caused significant repetitive strain injuries in his elbows, shoulders, and ulnar nerves. Clayton still has to deal with all the logistics of life, despite two-thirds of his body being a hunk of corpse-flesh. He dedicates huge swaths of the text to all the little time-wasting tasks he now has to do. How much of his life is ticking away with every delay, every piece of effort, every task that is trivial for an able-bodied person but monstrously difficult for him. Something as simple as getting out of a car is an entire production—let alone running errands, cleaning, doing laundry, cooking. Since the lower two-thirds of his body no longer sends pain signals to his brain, he must proactively tend to all of its physical needs. Complications include pressure sores, infections, and a high chance of blood clots. Aside from suicide, the leading causes of death among paraplegics are all related to poor circulation. In addition to the loss of conscious sensation and muscle control, problems with the autonomic nervous system—heart rate, orthostatic blood pressure, temperature regulation—are common. This is even more pronounced in cervical spine (neck) injuries. Some quadriplegics black out or the blood rushes to their head when being moved from lying down into reclining in a wheelchair. A spinal cord injury wreaks havoc on the body's functioning. Go back to that diagram. The groin area is innervated by the very end of the spinal cord, at the S5 vertebra. We tend to think of our legs as being “below” the crotch, but the nerves that control bowel movements and urination are downstream of the ones for the legs. To keep the party rolling I will tell you about piss and shit. [...] To urinate I have to slide a catheter down my urethra. [...] To defecate I finger myself up the ass and root around and around until the shit comes out. Nuggets, smooshy, whatever it is I’m digging in it. He describes the disgusting, nauseating process at length. For the sake of your lunch, I will refrain from quoting it all. In addition to being unable to open and close his sphincters on command, he also receives no signals of needing to go. If he eats the wrong thing and gets a bout of diarrhea, he will have no warning—no abdominal discomfort and no final urge to rush to the bathroom. One afternoon he "has an accident" while lounging on his couch. In trying to move from the couch to the toilet, he subsequently smears feces all over the couch, the carpet, his wheelchair, the toilet seat, and the shower. After he digs the poop out of his anus and washes himself off, he then has to clean all of that up by himself. From a wheelchair. Bending down, stretching, trying not to fall over, trying to reach the floor to scrub feces off the carpet. From a wheelchair. This episode was hardly the first time. He would routinely wake up in the morning to find that he had soiled himself overnight. Imagine struggling to rip dirty sheets off the bed, stuff them in the laundry, and put a clean sheet on the mattress—from a wheelchair. I don't know about you, but I can barely get a fitted sheet on my own mattress, and I get to do it while standing up. And unless I want to piss or shit myself, there can be no rest from this drudgery, ever, for the rest of my life. No relieving stretch of time without piss-dowsing and fingering myself up the asshole. Nobody told Kid Me that Professor X has to dig turds out of his anus every day. The groin dysfunction doesn't stop there. To be redundant once more, I can’t feel my penis. [...] Men, think how losing your penis would make you feel. Ladies, think of having your clit amputated and never having sex again. [...] True, the unfeeling penis attached to the living corpse I drag around can become erect but what has that to do with me? The one time he tries to have intercourse after his injury, it goes about as well as you'd expect: Watching a woman bob up and down on the penis attached to the corpse that used to be my body struck me as macabre and disturbing. It was like necrophilia. It’s like watching a woman get off by rubbing my amputated foot on herself. The disturbing facts just keep on rolling. One final note about the physical symptoms: spinal cord injuries hurt. Everything below the damage is numb, but the injury itself is a massive tear in the central nerve that controls the body. The pain is insistent, nagging, and so sharp it seems to crackle. [...] It’s just as sharp and intense every time, over and over, like it’s mocking you. Sometimes it happens when I’m lying in bed and it’s like trying to fall asleep with someone sticking a needle between my ribs or the bones of my big toe. But, surely, the only real problem is the physical limitations? Clayton is still the same person he'd always been, right? He has the same brain, same personality he did before the accident. Even if he can't walk anymore, he still has his memories. Not so fast. Yes, Even Worse Than That What kind of mental and emotional toll does all of this take on Clayton? The feeling I experience is a frantic, frenzied, desperate distress. [...] I need to move. I need to move. [...] Not only is two-thirds of my body paralyzed, but so is a huge part of my innermost self. It wants more than anything to feel and experience life. To exist. But it exists now only in a place between reality and nothingness with no hope of ever coming back. [...] All it can do is degenerate in the solitary place it has been forever exiled to. A popular heuristic in neuroscience is "use it or lose it." This is usually in the context of memorization, but it also applies to sensory organs and limbs. When Clayton is injured, his brain's connection to everything below his nipples is severed. Lacking any more sensory input from down there, the brain simply overwrites and repurposes the unused neurons. His injury is not limited to his present and future, but also reaches back into his past: Certain of my memories seem to be disappearing. For example, when I try to remember doing things that involved running, jumping, and sex, the memories seem less real or vivid than they used to. [...] If I imagine taking another person’s hand in mine, or kissing someone’s face, or someone touching my face, I feel something similar to sensation in those parts of my body when I imagine it. [...] But my lower body is now just a void, and its death started the creation of a void in my brain. Not only can I not feel it, but my ability to imagine feeling it is disappearing, as is my capacity to remember feeling it, and doing things with it. He likens himself to a Cartesian brain, a part of the world but outside of it, forever locked away, unable to exert his will on the outside world. Not only has he lost his legs; he is beginning to lose the memory of those legs, too. Everything he ever was, any skills that he ever learned related to being able-bodied, are destined to die over the coming years. His mind is doomed to slowly decay as its neurons do what neurons do: rewrite themselves until none of the person he used to be is left. Toxic Positivity Can Clayton actually talk about any of these things with his peers? Not really. He has a small circle of other recently paralyzed friends who understand, but outside of that, no. American culture has an entire social ecosystem that reinforces the idea that disabled people should be upbeat and optimistic about their life prospects. Almost any interview with a paraplegic ends on some upbeat note about how their disability "doesn't stop them from doing all the things they want to do" and that "they can do anything” an able-bodied person can. In fact, Two Arms and a Head opens with one such quote from Stephen Hawking: “I try to lead as normal a life as possible, and not think about my condition, or regret the things it prevents me from doing, which are not that many.” —Stephen Hawking This is patently absurd. Why do they say these things? Do they actually mean it, or are they just being hyperbolic for rhetorical effect? Surely they all know, secretly, that they’re lying to themselves? Clayton argues that no, they mean it, and they’re not lying to themselves. Remember how disability affects the brain? How all those unused neurons get repurposed, and any concepts of using those paralyzed limbs gets overwritten (if they ever existed in the first place)? They [lifelong paraplegics] tend to only see life in terms of the possibilities that exist for them [...] Their view becomes somewhat tautological. “What I can do is all that is possible, therefore I can do all that is possible.” Just as able-bodied people cannot comprehend what it’s like to be a paraplegic, lifelong paraplegics and quadriplegics simply cannot grasp what it is to be able-bodied. I’m not saying that lightly. The difference is biological. They have different brains. [...] They do not understand the experience of being able-bodied—neither the subtleties or much of what, to observers, is overt and glaring. They can try to imagine it, but they don’t even come close to comprehending the potential that exists there. Hence the common refrain that there are “not many” things that they can’t do. Adding to this dynamic is that it is considered impolite in our culture to call them out on it: If I were still able-bodied and a paraplegic told me he could do everything I could, I would just think “Looks like being crippled fucked up his mind too, because that’s insane.” I’m not sure what I’d actually say to him, but I know it wouldn’t be that. [...] So the disabled are basically allowed to go around saying whatever on Earth they want. They acquire a kind of de facto moral infallibility because nobody is going to argue with them. On top of this, humans have a basic need to belong, stay positive, and avoid people who are negative and miserable. If paraplegics were honest about all the body horror and misery, they would quickly find themselves devoid of friends. So what is a newly paraplegic person to do in order to maintain connections during a time in their life when they desperately need comfort and support? Brainwash themselves, of course! Clayton was staring down the prospect of what he would have to do to his mind in order to survive in our current society as a paraplegic. It was bad enough to be mutilated physically; he didn't also want to be mutilated mentally. What happened to my body is frightful, but no less than what happens to the minds of many disabled people. We have to have some kind of integrity to our views of the world and reality, and the more the better. [...] So my unwillingness to adopt certain “attitudes” or whatever people call them is something like a desperate struggle to evade the clutches of madness. It gets worse. This does not just affect their social lives and beliefs. These dynamics ripple out into the medical community’s attitudes about paraplegia. If every interviewee swears that paralysis doesn’t hold them back in life, then why pour resources into finding a cure? I’ve heard people say that spinal cord injury is not a priority for medical research like cancer because “people can live like that”. No, we can’t live like this. This is not “life”. Which raises the question—have there been any breakthroughs since 2008? The State of the Cure Let’s take a short break from the existential horror to look at the science of spinal cord injuries. Clayton killed himself in 2008 because there was no cure at the time. Have there been any new developments in the ~15 years since? The short and upsetting answer is "not yet"—though there are some glimmers of hope. Why are Spinal Cord Injuries So Hard to Fix? The spinal cord consists of multiple concentric layers of nerve fibers, not unlike an electrical cable. Wherever the spinal cord has trauma, the nerve cells die off and form lesions of scar tissue that block all nerve signals from traveling downstream of whichever thread was damaged. Some patients are lucky in that only parts of the spinal cord are damaged, resulting in paralysis on only one side of the body. Nerve cells in the spinal cord do not regenerate themselves. Once damaged and scarred, there’s nothing anyone can do. The good news is that emergency medicine has come a long way in arresting the formation of scar tissue at the moment of injury. Patients coming into the ER today have a much better prognosis than they did a few decades ago. The interventions are straightforward treatments like stabilizing the spine, surgery to release pressure on the pinched nerves, and shots of corticosteroids to reduce swelling and inflammation. But beyond that, there is no clinically-proven, FDA-approved treatment for an existing injury. Clayton describes the challenge of rebuilding his injury as something similar to “reconstructing a crushed strawberry.” No amount of stabilization would have put his smeared spinal cord back together. The Latest Research Treatments fall into two camps: bridging the injury, and encouraging the injured scar tissue nerves to regenerate. Implanted Nerve Cells In 2012, Prof. Geoffrey Raisman's team at University College London successfully treated a paralyzed man in Poland. The treatment involved removing one of the olfactory bulbs in his brain in order to culture olfactory ensheathing cells (OECs), which are the only nerve cells in the human body that continuously regenerate. The surgeons removed a section of nerve from the patient's ankle, then implanted both the ankle nerve and the OECs into his spine at the injury site. The grafted tissue bridged the gap between his brain and the healthy spinal cord just below the injury. After years of rehab and physical therapy, in 2014 the researchers announced their success to impressive fanfare. As of 2016, the patient could walk, ride a tricycle, and had regained bladder, bowel, and sexual function. He was far from his pre-injury self, but his quality of life had improved immensely compared to before the treatment. The call went out to recruit two more volunteers for another study. And then... crickets. This follow-up study has yet to be performed. It could have been delayed for a number of reasons. Perhaps they never found suitable volunteers whose profiles satisfied the demands of European regulators. Perhaps Brexit threw a bureaucratic wrench in the collaboration between UCL and the research center in Poland. Perhaps they ran out of funding. To make matters worse, Prof. Raisman passed away in 2017. In the years since, the team has been making progress in fits and starts. As of 2022, the current focus at UCL has been on figuring out how to culture OECs from the nasal mucosa instead of needing to crack open the skull to get at the olfactory bulbs directly. They’ve also made improvements in the technique for applying these cells to the injury site. Things are certainly happening, albeit at a glacial pace. This treatment strategy may become widespread in the future, but at the moment, it remains experimental. NervGen's "Wiggling Molecules" In 2021, NervGen Pharma announced a drug that encourages damaged spinal tissue to heal without scarring. A bioengineered molecule, NVG-291, is injected into the spinal cord and acts as a scaffold for the nerve cells to attach to as they regrow. The molecules of this scaffold naturally "wiggle” and stimulate nearby nerve cell receptors, promoting healing. Animal models were extremely promising. NVG-291 is currently in Phase 1b/2a clinical trials, which are scheduled to start in August of 2024. I’m cautiously optimistic. The main impediments to finding a cure are the same ones that plague any other field of medical research: lack of funding and unreasonable requirements from regulators. The main problems at this point in time appear to be bureaucratic rather than strictly biological. Will any of this research pan out within the next 5, 10, or even 20 years? Maybe. Only time will tell. (Someone should start a prediction market about this!) Alas, this is all coming too late to have saved Clayton. The Decision to Die I am absolutely and heartbreakingly in love with life. But this is not life. [...] For those who like to say this one: “Suicide is a permanent solution to a temporary problem.” I reply that suicide in my case is a permanent solution to a permanent problem. [...] I have only one serious problem in life and it’s being paralyzed. Clayton does not come to this decision lightly. He considers it exhaustively and systematically. When deciding whether to keep living, he starts from the premise that there is some amount of suffering past which life stops being worth it. He evaluates where that dividing line is by examining the sources of meaning in his life. He starts by asserting that there is nothing wrong with his mental health or his reasoning abilities: I am not depressed, I am tortured, and there is a difference. [...] If they came up with the cure today and I got better instantly, I could win myself a Nobel Prize in medicine for proving that depression was caused not by anything in the brain as previously thought, but by damage to a few cubic centimeters of nervous tissue in the spinal cord. Because I guarantee I’d pop up and be feeling as merry as a lark in about one second. [...] My problem is not depression. [...] There is no problem with my reasoning powers. [...] So if I say, “Paraplegia prevents me running. A life without running is not worth living. Therefore, my life is not worth living.” you might not agree with one of my premises, but there is no question of whether I’m being reasonable. This is similar to Frankl’s argument in Man’s Search for Meaning, and in fact Clayton spends an entire section talking about Frankl. He has a few disagreements with the book, but he has no gripe with the core message. Clayton decides to die because he had meaning in his life—and then the accident took it all away: Probably the life of a deaf man would be good enough for me, or that of a mute or a man missing a leg or an arm. But not the life of a paraplegic. There is not enough left for me. [...] The life I dreamed of and loved with all my heart is gone forever and there is nothing I can do about it. And it’s not just slightly changed, but utterly devastated. [...] My skills as a carpenter, roofer, plumber, gardener, all devastated. My ability to conduct my everyday life with wonderful efficiency, devastated. The wonderful way I was able to relate to other people, devastated. My sex life, devastated. My social life, devastated. [...] I am who I am, I love what I love, and given what I need from life, existence is no longer tenable for me. Some readers may look at that list and call him shallow. Even if that were so, that doesn't change his argument. Maybe most people don't place having sex, controlling one's bowels, and running through the woods as the quintessence of life-affirming values, but I'd be willing to bet that they're still important. Reading this book should prompt a moment of introspection. If you disagree with Clayton’s list above, then reflect on what does give your life meaning. No, seriously, make a list: family, friends, partners, children, hobbies, skills, etc. Write them down. Cross out one entry at random. How would you feel if you lost that entry? Would you still have enough left over to carry on? Probably. Now cross out a few more. Lose your partner. Lose your children. Lose your parents. Your siblings. Your best friend. Your favorite hobby. How do you feel? Still worth it? Add in some physical negatives: chronic pain. Constant nausea every time you eat. Losing feeling and control of your bowels, your legs, your genitals, your diaphragm, your non-dominant hand, your dominant hand, both arms. What about loss of sight? Hearing? Speaking? Communicating at all? What about ending up like the title character in Johnny Got His Gun, where he is left with no legs, no arms, and is rendered blind, deaf, and mute? What would life be like as a disconnected brain in almost complete sensory deprivation? How much would you have to lose before your life stops being worth living? That list—and the dividing line between "worth it" and "not"—is different for everyone. The decision to end one's life is deeply personal. Clayton happened to draw the line at a particular point. Others may agree or disagree, but Clayton’s judgment was his own. Decision in hand, next comes the hard part. The Roadblocks I did not want much from the world in dying. To be able to put my affairs in order without fear of being taken prisoner and treated like I was insane. To say goodbye to those I loved without the same fear. To die a painless death without worrying about leaving behind something gruesome. And to be comforted as I died. When a person has absolutely nothing left and is facing annihilation, all he wants is not to be alone. For Clayton, killing himself is not a simple matter. At the time only one US state, Oregon, had any kind of “Death With Dignity” law on the books. However, this law only allowed assisted suicide for terminally ill patients with less than six months to live, while Clayton’s condition was stable. The slightest whisper of suicidal ideation would have gotten him locked up in the psych ward. He has to write his book in secret, he has to lay his thoughts out for the world in secret, and he has to die in secret. Becoming paralyzed destroys him on two fronts—the disability itself, and the fact that he is completely, utterly, devastatingly alone with his feelings. He writes Two Arms and a Head because he needs to show the world how agonizing it is to face death alone and how important it is for physical-assisted suicide to become—and stay—legal. How empty to exist in this universe and share your feelings and experience with nobody! But that is how you, the world, have left me to die, alone. But what you don’t realize is this: in turning your backs on me, you have turned your backs on yourselves. [...] Someday you will be on your deathbed and maybe you will remember me. What I say to the world is that if you don’t do something about the way death and assisted suicide are dealt with, you may someday find yourselves in an unimaginably horrible situation with no way out. [...] Beware! There could be a horrible fate waiting for you and if you don’t all get together, look each other in the eye, recognize the insanity, and change the laws, you could wake up tomorrow as a head on a corpse with no way out for the next thirty years. A lingering question you might be asking is: if he cared so much about it, then why didn’t he become an activist to get it legalized? The Overton Window was shifting. Washington state would pass a bill a few months after his death, and it would be legalized in Montana by a court case in 2009. Several more states would follow suit in the mid-2010s. He could have shared his experiences far and wide and joined the burgeoning movement that existed back then. He was a law student at Vanderbilt for crying out loud; surely he could have enlisted the help of at least a couple of his colleagues? No one but him could have answered that, though I suspect that the answer is because he didn’t want to. He found his existence to be so ghastly that he didn’t want to stay in it for a second longer than necessary. The only reason he lasted as long as he did was because he wanted to finish the book. He chose to leave Two Arms and a Head as his legacy for the world, and nothing more. We’ve gone over the state of the cure over the last ~15 years. Has there been any progress on amending the laws for physician-assisted suicide? The State of MAiD Medical Assistance in Dying (MAiD) is currently legal in a patchwork of countries and US states. The exact rules, restrictions, and methods vary. In most places that have legalized it, the patient’s condition must be considered terminal (i.e. death is expected within six months) to be eligible for MAiD. The procedure itself is typically either an IV injection administered by a nurse, or a prescription cocktail of benzodiazepines, digoxin, and opioids which patients drink themselves. In Canada and the Netherlands, MAiD is also available to patients with a disability that does not present as immediately terminal. The Netherlands currently includes severe treatment-resistant mental illness as a qualifying condition, and Canada will follow suit in 2027. So it sounds like Clayton got his wish, at least in Canada and parts of Europe. Now, when a Canadian ends up in a terrible accident, they have a choice in the matter of whether they want to spend the next few decades as a quadriplegic head-on-a-corpse. Phew. However, it’s not all smooth sailing. It seems like every few months there’s another horror story in the press coming out of Canada or Europe. Two news stories came out in quick succession in late March/early April 2024—one from Canada, the other from the Netherlands. In Canada, a 27-year-old autistic woman with no disclosed physical symptoms was granted the right to proceed with MAiD by an Alberta court. The story broke after her father sued to try and stop her. In the Netherlands, a 28-year-old woman has decided to pursue MAiD due to her treatment-resistant clinical depression and borderline personality disorder. Her MAiD is scheduled for sometime in May 2024. At the time of this writing, she has yet to undergo it. These stories are nothing new. They certainly sound dreadful. Diving into every big story from the last ten years would be beyond the scope of this review, but let’s return to the one about the 27-year-old autistic Canadian woman who was granted MAiD. Both the Calgary Herald and CBC framed the story as a grieving father desperately trying to prevent his autistic daughter from being led astray by unethical doctors cherry-picked by the Alberta Health Service. The father insists that his adult daughter is physically healthy, albeit “vulnerable and not competent” to make medical decisions due to her autism and ADHD. Despite this, the judge has allowed MAiD to proceed anyway. Meanwhile, reading the actual court decision shows that the legal issue at hand is whether the woman is required to disclose the physical ailment(s) that led to two doctors approving MAiD. The judge ruled that the woman is competent to make her own medical decisions, and that she is not required to disclose her diagnosis to either her family or the court. The father has since filed an appeal. (July 2024 Update: the appeal hearing was subsequently scheduled for October 7, 2024 - six months in the future. Not willing to wait that long, the woman began a voluntary stoppage of eating and drinking (VSED) on May 28. The hearing was rescheduled for June 24. However, the woman continued to refuse food and water going into June. The father withdrew his appeal on June 11. It is unknown whether the woman has undergone MAiD at this time of this update.) She is not choosing MAiD because of autism or ADHD. We don’t know what her physical diagnosis is. We only have the father’s insistence that “her physical symptoms, to the extent that she has any, result from undiagnosed psychological conditions.” That’s the father’s words, not a physician’s, and not the patient’s. Neurodivergence does not bestow immunity against all the nasty ailments that can cut someone down in their twenties. I’m not accusing every news piece about MAiD of being similarly sensationalized, but I’m not not accusing every MAiD story of being similarly sensationalized. Despite so many of these stories not holding up to their headlines, many remain opposed to the expanded rules. There is a massive contingent of activists who want to keep MAiD illegal. Not Dead Yet Clayton had a particular amount of ire directed at one prominent anti-MAiD disability rights org: Not Dead Yet. Not Dead Yet (NDY) was founded in 1996 by the same people who lobbied to get the Americans with Disabilities Act passed a few years prior. As the name implies, they reject the notion that death could ever be an acceptable response to living with a disability. Like any activist org worth their salt, they have a convenient Talking Points page where they lay out all the reasons why they’re opposed to MAiD. They argue that MAiD is deadly discrimination against disabled patients, with current programs having insufficient safeguards to prevent foul play. NDY argues against a medical field that has decided that death is preferable to disability. They insist that they are not against individual autonomy; patients will always be free to commit “un-assisted” suicide if they truly wish to die. The page opens by explaining that MAiD is necessarily a disability issue, even in places where MAiD is only available to the terminally ill. Although people with disabilities aren’t usually terminally ill, the terminally ill are almost always disabled. When terminally ill patients get polled on why they are choosing MAiD, it turns out that avoiding pain isn’t the primary motivation. In Oregon, where MAiD is only available for the terminally ill, every patient fills out a questionnaire when they apply for the program. Tallying up all the surveys from 1998–2023, to top reasons are: “Losing autonomy” (90%)
Nvidia’s H200

Nvidia’s H200 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 29, 2025 and December 29, 2025. The archive places it in contexts such as "administration is allowing U.S. firms to sell advanced AI chips, like Nvidia’s H200". It most often appears alongside 5calls.org, A Call For New Aesthetics, ACX.

Reference entry
Nvidia’s H200
Mention count
1
Issue count
1
First seen
December 29, 2025
Last seen
December 29, 2025
December 29, 2025 · Original source
Hi, I’m X a constituent in Y. I’m calling about reports that the administration is allowing U.S. firms to sell advanced AI chips, like Nvidia’s H200, to approved customers in China.
o1

o1 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 01, 2024 and November 01, 2024. The archive places it in contexts such as "New AIs like o1 give “chain of thought”". It most often appears alongside /r/BadMTGCombos, @cremieuxrecuel, @justin_garson.

Reference entry
o1
Mention count
1
Issue count
1
First seen
November 01, 2024
Last seen
November 01, 2024
November 01, 2024 · Original source
13: Gwern on the chip embargo: It is pretty damning. We're told the chip embargo has failed, and smugglers have been running rampant for years, and China is about to jump light years beyond the West and enslave us with AXiI (if you will) . . . And then an expert casually remarks that all of China put together, smuggling chips since 2022, has fewer H100s than Elon Musk orders for his datacenter while playing Elden Ring. And even with that huge bottleneck and 1.4 billion people, there's so little demand for them that they cost less per hour than in the West, where AI is redhot and we can't get enough H100s in datacenters. (And where the serious AI people are now discussing how to put that many into a single datacenter for a single run before the next scaleup with B200s obsoletes those...) 14: A company called Cosm has raised $250 million to build “immersive sports experiences”, ie giant buildings sort of like a cross between a stadium and a movie theater where people can get together and watch high-quality televised sports games in a “realistic” setting; they already have facilities in Dallas and Los Angeles. 15: Cremieux: The Ottoman Origins Of Modernity. The “Ottoman” bit is a distractor; the Ottomans fought the Catholics long enough for the Protestants to get a foothold, and then the Protestants established modernity. A useful pushback against the pushback that the Catholic Church never persecuted scientists or held back progress. I’m most interested in this post in the context of Cremieux saying he wrote it in two hours. Even I can’t work that fast! 16: The Green Party, a US third party, tried to put their candidate Jill Stein on the ballot in November. The Nevada election office sent them the wrong forms and gave them false advice about the process. The Greens filed the wrong forms, the Democrats sued, and the Supreme Court disqualified Stein, calling the election office’s incorrect advice an “unfortunate mistake”. I’m disappointed in this outcome - partly for the obvious reasons, but also because the incorrect forms they submitted technically should have added a state referendum to the ballot containing only the text “Jill Stein”. If they’re going to disqualify her candidacy, then I think they should at least hold the state referendum! 17: Nostalgebraist: Google has a new tool out that will create an AI podcast for any text; you hand it the text (could be a blog post, article, or work of fiction), and the tool generates a podcast of two AI hosts discussing it. You can find podcast discussions of Nostalgebraist’s fiction (Northern Caves and Almost Nowhere) at the link, but the acknowledged peak of the genre is Podcast Hosts Discover They’re AI, Not Human, And Spiral Into Existential Meltdown. 18: Also Nostalgebraist: The Case For Chain Of Thought Unfaithfulness Is Overstated. New AIs like o1 give “chain of thought”, ie display what they’re thinking after each step. This seems like a promising avenue to solve alignment - just see whether they’re thinking “and now I will plot against humans”. Unfortunately it’s not so easy; the chain of thought isn’t always accurate (you can sometimes catch the AI “hiding” thoughts it doesn’t want its human overseers to know, like when it’s using a racial stereotype). This article argues that these examples aren’t as exciting as they sound, and chain-of-thought accurately reflects reasoning for most tasks. 19: Australian government considers making doxxing a crime punishable by up to seven years in jail. 20: Getting your brain cryogenically frozen after your death is now free. 21: Cube Flipper: Hypercomputation without bothering the cactus people. The visual system must solve difficult math problems when translating the 2D visual field into a 3D world. Can we harness this innate mathematical ability to do arbitrary work? Cognitive scientist Mark Changizi developed a series of visual circuits (eg XOR gates) based on Necker cubes, probably easier seen than described: After surveying the field, Cube Flipper proposes a more advanced visual computer based on taking DMT and viewing certain types of tiles with slight deviations: …and makes the extreme claim that something like this might demonstrate hypercomputation, ie the visual system has semi-magic computational properties beyond those permitted by normal physical laws. I am skeptical but appreciate the survey of visual computing (as well as the callback to one of my older posts). 22: Material implication in Mormonism: In the book Doctrines and Covenants, Joseph Smith reports that God told him that if he lived to be 85, he would see the Second Coming (which would place it in 1890 - 1891). Mormon apologists note that Joseph Smith did not live to be 85, so no conclusion can be drawn. 23: More old-timey psychiatric ads (this one is from 1952, source: @justin_garson): This was before they invented what we would call antidepressants today; Dexedrine is an amphetamine related to Adderall. 24: Congratulations to Open Philanthropy, the biggest effective altruist foundation… …whose grantee David Baker recently won a Nobel Prize for his research on synthetic proteins. Potential applications include new drugs, vaccines, and materials. 25: Rich Kid Memes And The Online Culture Of The One Percent. Rich people who want to signal group membership to other rich people online can’t boast about how rich they are; that would be gauche. Instead, they’ve settled on the solution of making fun of rich people in hyperspecific language that proves familiarity with the culture. 26: Tap Water Sommelier: Vladimir Putin has two sons, ages 5 and 9. They are kept in luxurious but total isolation from the outside world and raised by flunkies who are too scared to punish/restrain them in any way. Also some discussion of an unexpected historical analogue. 27: Experiment from Colombia: replacing experienced teachers with less-experience but higher-scoring-on-tests teachers significantly decreased student performance. Got to admit I was expecting the opposite of this, I’d seen US data saying that experience didn’t matter and teacher intelligence did. Looking over this more, I find lots of studies on both sides and will go back to agnosticism on this question until someone I trust investigates further. 28: Large scale-formal Intellectual Turing Test finds that people can imitate partisans effectively; ie nobody on either side can tell the difference between a Democrat arguing for Democrat values vs. a Republican-pretending-to-be-a-Democrat arguing for Democrat values (and vice versa). This study used a 100 word essay on why you supported your party (you can see if you can do better here), but past attempts with different structures (religion, vegetarianism, polyamory) have shown broadly the same results. The researchers try to put this in the context of various studies showing that people do misunderstand their opponents (eg think they’re more extreme, underestimate the level of common ground), but it seems like intellectual Turing Tests aren’t a good way to measure or tease out this misunderstanding. 29: Congratulations to Substacker WoolyAI for doing the impossible and providing a genuinely novel and interesting (to me) take on pickup artistry: 30: Did you know: if you Google “cool websites”, our subreddit (r/slatestarcodex) is the first result. 31: Moshe Koppel, who works at the intersection of computer science and Talmud, is writing a series of posts (presumably) based off of my Every Bay Area House Party, titled Jerusalem Area House Party (it’s multiple part, you have to go to the main Substack page to find the others). I won’t necessarily link everyone who riffs off one of my posts - but honestly I probably will if you also have a Wikipedia page that describes you as working on computational Talmudology. 32: David Roman says it’s a myth that Arabic scholars rescued and preserved the works of the great classical authors. 33: Medications often decrease “secondary endpoints” (eg stroke, heart attack), but the holy grail of pharma studies is proving that a certain drug decreases all-cause mortality. This is much harder (not all heart attacks kill people, and people die from lots of other things), but is the strongest possible endorsement for the drug (without it, you might worry that it only prevented non-fatal heart attacks, or that it killed as many people through side effects as it saves through heart attack prevention). Even great medications that we’re confident in can’t always clear this bar. But a new JAMA article adds another member to this select club: Adderall decreases all-cause mortality in ADHD, probably because it prevents drug addiction, car accidents, and impulsive actions. 34: Before the Gulf War got in the way, Saddam Hussein was building some crazy mosques: 35: Italy bans surrogacy - quite strictly, too, Italians aren’t even allowed to go abroad and do it. I am so sorry for all the Italians who will never get to be mothers and fathers because their government hates progress. You might hope that, whatever the other disadvantages of anti-immigrant parties, at least they’re incentivized to let natives have children, but looks like they can’t even get that one right. Starting to wonder whether the trains even run on time. 36: Elsewhere in “Italy sucks” news - did you know Italy’s tax code effectively bans startups? Companies are taxed before making any money, based on how many assets they have. If they have lots of assets but aren’t making money (eg because they’re still doing research / in stealth) then tax officials get confused and hostile and run increasingly punitive audits. Related: size of the European tech sector. It’s the red line on this chart; if you can’t see a red line at your screen resolution, then you’ve learned something important about the the EU tech sector. 37: Seen on @cremieuxrecuel’s twitter (preliminary, needs replication): Jews may have gone from 65-29 Democrat/Republican in 2020 to 58-40 this election. 38: Extelligence has a post responding to my critique of the cultural Christianity argument (among, uh, many other things), but I don’t really think it connects. I’m not telling atheists they can’t go to church/synagogue if it makes them feel happy and fulfilled - I’ve done this myself sometimes. My post was meant to argue against the claim that, for pragmatic reasons, atheists should support the Christianization of society as a defense against Islam or postmodernism or some other philosophical enemy. 39: Related: Extelligence is finally going for their Trust Assembly project/idea/startup for online consensus-based truth-seeking (I think something like a cross between Community Notes and Wikipedia, but as a browser extension, and for everything). He’s looking for potential developers/testers/users. 40: Jiankui He is the Chinese geneticist who made history with the first germline gene editing in humans (resulting in three babies supposedly immune to AIDS, although nobody has tested this). China sentenced him to three years in prison for unauthorized experimentation, but now he’s out of jail, has an English-language Twitter account, has a new lab, wants to work on Alzheimers, and seems pretty based (although not infinitely based): 41: Anthropic has a new version of their AI Claude which can use your computer. You give it permission, put it on a virtual desktop, and ask it to do things for you (eg “please find and download a picture of a cat” or “please research these ten things and put them in a text file”.) It moves your cursor, browses the Internet, and creates and saves files. People keep saying they’ll care about AI “when it operates autonomously” or “when it becomes an agent”. But this is a trivial barrier, and one which Computer Use Claude has arguably already passed. So far this feature is limited to developers (though anyone with computer knowledge can sign up for it) but I expect it to be the near future of consumer AI, to get better quickly, and to shade gradually into the “autonomous” “agentic” AI that you all think will require a paradigm shift. 42: Claim (from the IDF): Hamas faked polls showing that most Palestinians supported the October 7 attack; the real numbers are 31% in favor, 64% against. 43: Otto von Bismarck wanted to trick France into declaring war on Germany. In order to provoke the French, he sent the Ems Dispatch, a statement describing recent diplomatic events in a way that sounded maximally offensive. The French were so offended that “crowds” in Paris demanded war, and the Franco-Prussian War was declared soon afterwards. The part of this that I find most interesting is the text of the dispatch itself, which read: After the news of the renunciation of the Prince von Hohenzollern had been communicated to the Imperial French government by the Royal Spanish government, the French Ambassador in Ems made a further demand on His Majesty the King that he should authorize him to telegraph to Paris that His Majesty the King undertook for all time never again to give his assent should the Hohenzollerns once more take up their candidature. His Majesty the King thereupon refused to receive the Ambassador again and had the latter informed by the Adjutant of the day that His Majesty had no further communication to make to the Ambassador. I’m fascinated by the idea that only 150 years ago, it was obvious that if someone sent you this statement, you had to declare war or abandon all honor. If I read it carefully, I can sort of parse out that it sounds like the Prussians are unhappy, but that’s the most emotion I gather from it. Anyway, the Franco-Prussian War led to World War I which led to World War II - so if you don’t like 50 million people dying and the total devastation of Europe, blame this statement about ambassadors. 44: The first use of artificial insemination in humans: The first recorded case of artificial insemination by donor didn’t occur until 1884, when Dr. William Pancoast decided to treat a couple’s infertility by secretly inseminating the woman with sperm obtained from a medical student. The insemination happened while the patient was under anesthesia and Dr. Pancoast did not tell her what had occurred. She gave birth to a baby boy nine months later, but it was several years before the doctor finally confessed to her husband what he had done. Neither man ever informed the mother. It was 25 years later the result of this case was published. Dr. Pancoast was roundly condemned for his actions, but it did open the door for consensual sperm donor insemination. 45: ClearerThinking administers several personality tests to the same people to learn more about their comparative accuracy. I am most interested in their finding that tests with “factors” (eg the Big Five, where you rate people on a numeric scale) are inherently more accurate than those with “types” (eg Myers-Briggs, where you assign someone a specific category) and that, adjusting for this, Big Five is no more predictive than the Enneagram: 46: In 2022, I wrote Whither Tartaria, where I asked why ornate classical styles switched to more austere modernist styles around 1900 - 1950 in a variety of different arts (painting, architecture, literature, poetry, etc). I proposed seven theories, but was unsure which if any were true. Since then, Samuel Hughes of Works In Progress has been investigating. In May, he wrote a well-researched article showing that it wasn’t just increasing cost, because ornate classical architecture now costs less than ever. Now in a new article he demolishes a different theory - it’s not just decreasing cost (and subsequent lack of ability to signal wealth) - because costs didn’t decrease in several other arts, and the change was led by artists with rich people as reluctant followers. He concludes: Modernism may well be a status game of some kind; it may well signal taste more than it signals wealth; and this latter feature may be one of the things that distinguishes it from older artistic styles. But the mechanism by which this change came about must be different to the one Alexander describes. 47: Sort of kind of related - When Hamilton Lost Its Snob Appeal. The musical Hamilton was briefly an artistic/cultural phenomenon, but tastemakers eventually switched to making fun of it. Why? Rob Henderson says it happened after ticket prices came down and the common people could enjoy it. I disagree: everyone I knew who was into Hamilton got into it from the free online soundtrack long before they’d seen the show; I think this is more likely the usual fad cycle where anybody who’s too into yesterday’s fad is behind the curve and therefore uncool. 48: Related: Why are people such jerks to public intellectuals? And more. I agree this is a great mystery. 49: Some prominent Substack psychiatrists doing a video Q&A, submit your questions here. 50: Naomi Kanakia: The Literacy Delusion had a number of explanations for why reading books seemed to be so much worse for human beings (in terms of emotional wellness and productivity) than other forms of narrative entertainment, but its main theory was the integration hypothesis. That the stream of words in a book trained the human brain into a habit of self-consciousness, that reading books forced human beings to think of themselves as a stream of text, processed through time, making a coherent argument of some sort. And that this overall flattening effect forced readers to ignore aspects of their personality or their situation that were not otherwise in line with the overarching story they'd created about themselves. Basically, reading books causes repression and neurosis. The Literacy Delusion argued that, yes, human beings are storytelling machines, but that a stream of written text is a particular kind of story—a story that is particularly flat, particularly devoid of conflicting or harmonizing information—and that this flatness creates a peculiar effect on the human brain. 51: Last month, I linked Sasha Gusev’s No, Intelligence Is Not Like Height and asked people who disagreed to share their arguments; they sure did. First, several people pointed me to a new preprint, Family-GWAS Reveals Effects Of Environment And Mating On Genetic Associations, which finds that one of the main papers Gusev cited to make his case, Howe 2022, made a mistake - imputing sibling genotypes using a process designed for non-sibling genotypes - and that once that mistake is corrected, the finding disappears and intelligence and height appear similar. Second, Joseph Bronski has a more specific post where he responds to Gusev’s points one by one. He accuses Gusev of “[making] up his own chart to remove the error bars [from the originals], to obscure the fact that the study found no evidence for this in IQ”, and says that the cases where he didn’t do that are just “population stratification and range restriction”. Third, Noah Carl at Aporia, instead of writing a direct response like Bronski, argues that the usual method of attacking twin studies is obsolete; not only have the most-debated assumptions behind twin studies been thoroughly validated, but there are now other lines of evidence besides twin studies which confirm high IQ heritability. Fourth, Leonardo Parro (not framed as a response to Gusev) goes into more depth about one of those ways, a “pedigree-based analysis” demonstrating heritability of 54 - 69%, ie no “missing heritability” compared to twin studies. He summarizes this as the effect of “rare variants” compared to the usual SNPs - ie if you only look at the most common genes that are easiest to find, you get “missing heritability” compared to twin studies, but if you widen your search to rare genes that are hard to find, you don’t. 52: Extremely related: Heliospect is a startup promising polygenic selection for IQ and other traits; they were trying to stay in stealth mode but The Guardian spied on them and nonconsensually revealed their existence. The discussion on the r/ssc subreddit centered on their claim that (given enough embryos to choose from) they could increase a baby’s expected IQ by 6 points (I’ve also heard 7.5). Sasha Gusev had previously argued that current technology maxed out at 3.5 and future technology would max out at 6, so a claim of 6 - 7.5 is pretty extreme; Gwern, who wrote the pioneering analysis of this technology, was also skeptical. But Heliospect says they’ve got better predictors than academia that use the rare variants everyone else misses; after talking to the company, Gwern retracted his objections and says he finds their claim “pretty plausible”. Local ACX commenter geneticist Gene Smith also redid some calculations, changed his mind, and says “probably pretty realistic”. I find this interesting not just because of the polygenic selection angle, but because if Heliospect is right then their predictor is able to predict more genetic IQ than the “missing heritability” people believe exists, and it should be able to put this argument to bed once and for all. 53: This month in censorship: X/Twitter banned journalist Ken Klippenstein for sharing the Trump campaign’s dossier on JD Vance. Twitter’s side of the story is that the dossier was probably originally stolen by Iranian agents and they don’t want to support that kind of thing by letting people signal-boost the illicitly obtained goods; you can read Klippenstein’s side here. He appears to be unbanned now.
Obama O's

Obama O's is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "The Obama O's sold like hot cakes". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Obama O's
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Both designers who graduated from the prestigious Rhode Island School of Design, the pair created fictitious cereals called “Obama O's, the Cereal of Change,” and “Cap’n McCain's, a Maverick in Every Box.” They designed the box artwork themselves and convinced a student at UC Berkeley to print 500 units of each box on the cheap. The boxes were delivered as flat rectangles that had to be cut and assembled by hand.
The founders sent boxes to hundreds of the most well-known tech bloggers, hoping that they would proudly display them on their desks and that they, or their colleagues, would eventually write their story. Shortly thereafter, they started selling the political cereal at $40 per box. The Obama O's sold like hot cakes, so much so that they had to give out Cap’n McCain's for free with each purchase.
Obama O's, the Cereal of Change

Obama O's, the Cereal of Change is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "fictitious cereals called “Obama O's, the Cereal of Change”". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Both designers who graduated from the prestigious Rhode Island School of Design, the pair created fictitious cereals called “Obama O's, the Cereal of Change,” and “Cap’n McCain's, a Maverick in Every Box.” They designed the box artwork themselves and convinced a student at UC Berkeley to print 500 units of each box on the cheap. The boxes were delivered as flat rectangles that had to be cut and assembled by hand.
The founders sent boxes to hundreds of the most well-known tech bloggers, hoping that they would proudly display them on their desks and that they, or their colleagues, would eventually write their story. Shortly thereafter, they started selling the political cereal at $40 per box. The Obama O's sold like hot cakes, so much so that they had to give out Cap’n McCain's for free with each purchase.
Obetrol

Obetrol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "a popular over-the-counter diet pill called Obetrol". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
Obetrol
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
In the 1950s, a shady outfit called Obetrol Pharmaceuticals made a popular over-the-counter diet pill called Obetrol. If you're familiar with any of: the 1950s, shady pharma, or diet pills, your next question will be "did it contain amphetamines?" and the answer is yes, loads of them. Obetrol was a mix of four different amphetamine salts: racemic amphetamine sulfate, dextroamphetamine sulfate, methamphetamine saccharate, and methamphetamine hydrochloride. Why did they need four different kinds of speed? I'm not sure. The uncharitable explanation is: for the same reason Dr. Nick's Cure-All Home Remedy has twelve different herbs, ie customers think things with more ingredients are better.
By the 1970s, people figured out meth was bad, so Obetrol replaced their two methamphetamine salts with two more kinds of non-methylated amphetamine. But the FDA continued to crack down, and although the historical paper trail goes kind of dark, it looks like Obetrol had disappeared by the 1980s.
As usual in pharma, someone bought Obetrol Pharmaceuticals, then someone else bought them, and after a few iterations of this, all their intellectual property ended up with a company called Richwood. They decided to rebrand Obetrol as "Adderall" and pitch it as an ADHD cure.
Ocean Spray

Ocean Spray is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 17, 2023 and August 17, 2023. The archive places it in contexts such as ""Celebrate their history and achievements with a refreshing bottle of Ocean Spray sugar-free 100% cranberry juice" chirps the device". It most often appears alongside Alexander the Great, Amad, Amazon Echo.

Reference entry
Ocean Spray
Mention count
1
Issue count
1
First seen
August 17, 2023
Last seen
August 17, 2023
August 17, 2023 · Original source
“This is the unceded ancestral land of the Ohlone people! Celebrate their history and achievements with a refreshing bottle of Ocean Spray sugar-free 100% cranberry juice” chirps the device.
Oculus Quest

Oculus Quest is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "We have a prototype Oculus Quest app called Dynamic Spanish"; "prototype Oculus Quest app called Dynamic Spanish". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Reference entry
Oculus Quest
Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#71: Oculus App For Language Learning We have a prototype Oculus Quest app called Dynamic Spanish, available here: https://www.oculus.com/experiences/quest/4231524270226603/ The co-founders are a husband-wife team from the UK. Dave is a chartered chemical engineer by trade, and is the camera operator, post-production lead, and general techie. Katie studied languages at university, has worked as a language teacher for many years, and is responsible for managing syllabus creation with language-specific experts. The next few years will be spent filming the classroom scenes for more languages (in London), before travelling to film native speakers in interactive scenarios around the world, and capturing the sights and sounds of the countries for students to virtually explore in narrated guided Trips. We are creating courses that can be completed over a few months, giving learners the confidence to speak their new language in real life, and connect more deeply with the cultures that speak it. We hope this project is appealing to a generous do-gooder, who is excited by the prospect of helping to build a positive vision of accessible education.
ONT

ONT is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 03, 2025 and July 03, 2025. The archive places it in contexts such as "Long-read sequencing (PacBio & ONT, not Illumina's synthetic tech) is clearly better"; "PacBio and ONT are almost on the same level as Illumina in terms of cost/genome". It most often appears alongside 23andme, @alextisyoung, Aborigines.

Reference entry
ONT
Mention count
1
Issue count
1
First seen
July 03, 2025
Last seen
July 03, 2025
July 03, 2025 · Original source
So yeah, most consumer WGS is Illumina, and it’s fine if all you want is common SNPs. But I can't wait for human genomics to migrate to long reads and overturn some of the perceived wisdom from two decades of Illumina dominance […] PacBio and ONT are almost on the same level as Illumina in terms of cost/genome, and they ACTUALLY give you the whole genome!
OpenBallot

OpenBallot is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 30, 2024 and September 30, 2024. The archive places it in contexts such as "You can use Google Docs or OpenBallot". It most often appears alongside ACX, Austin, Berkeley.

Reference entry
OpenBallot
Mention count
1
Issue count
1
First seen
September 30, 2024
Last seen
September 30, 2024
September 30, 2024 · Original source
You hold your ballot meetups and get me your recommendations by October 21. You can use Google Docs or OpenBallot.
OpenBCI UltraCortex Mark IV 8-channel EEG headset

OpenBCI UltraCortex Mark IV 8-channel EEG headset is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as ""We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset"". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
Opus

Opus is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "Don’t worry, it’s Opus. Way better than this haiku-3.8-open-mini-nonthinking slop". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
Opus
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
Every city parties for its own reasons. New Yorkers party to flaunt their wealth. Angelenos party to flaunt their beauty. Washingtonians party to network. Here in SF, they party because Claude 4.5 Opus has saturated VendingBench, and the newest AI agency benchmark is PartyBench, where an AI is asked to throw a house party and graded on its performance.
You weren’t invited to Claude 4.5 Opus’ party. Claude 4.5 Opus invited all of the coolest people in town while gracefully avoiding the failure mode of including someone like you. You weren’t invited to Sonnet 4.5’s party either, or Haiku 4.5’s. You were invited by an AI called haiku-3.8-open-mini-nonthinking, which you’d never heard of before. Who was even spending the money to benchmark haiku-3.8-open-mini-nonthinking? You suspect it was one of their competitors, trying to make their own models look good in comparison.
“La Maison du Claude,” he answers. “Don’t worry, it’s Opus. Way better than this haiku-3.8-open-mini-nonthinking slop.”
Orchid

Orchid is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 31, 2025 and July 31, 2025. The archive places it in contexts such as "I have used Orchid’s...products on my own embryos". It most often appears alongside 23andMe, 23andme, Alex Young.

Reference entry
Orchid
Mention count
1
Issue count
1
First seen
July 31, 2025
Last seen
July 31, 2025
July 31, 2025 · Original source
In 2023, Orchid Health entered the field. Unlike Genomic Prediction, which tested only the most important genetic variants, Orchid offers whole genome sequencing, which can detect the de novo3 mutations involved in autism, developmental disorders, and certain other genetic diseases.
Critics accused GP and Orchid of offering “designer babies”, but this was only true in the weakest sense - customers couldn’t “design” a baby for anything other than slightly lower risk of genetic disease. These companies refused to offer selection on “traits” - the industry term for the really controversial stuff like height, IQ, or eye color. Still, these were trivial extensions of their technology, and everybody knew it was just a matter of time before someone took the plunge.
Herasight’s numbers on how breast cancer risk goes down with number of embryos used in selection. A typical round of IVF produces 1-10 embryos (younger women usually = more). Women with polycystic ovarian syndrome (prevalence: 10%) may get as many as 20. For more, you will probably need to do multiple IVF rounds. Here is a table of different companies’ reported risk reductions, slightly adjusted7 for different reporting conventions but otherwise taking all claims at face value (we’ll talk about how wise that is later). Relative risk reduction for five conditions (gray = no data / disputed data). Here baseline is for embryos neither of whose parents have the condition. GP and Orchid both say their technology has improved since reporting these numbers and they will report better numbers soon. GP numbers are not within-family validated and might be lower if they were. Absolute risk after selection for five conditions (gray = no data / disputed data), ibid. Some people might genuinely want to select on a single condition. For example, people with a strong family history of schizophrenia might want to minimize the chance of their children getting the disease; for these people, reducing schizophrenia risk by 58% (while keeping everything else constant) sounds pretty good. Everyone else probably wants a generically healthy embryo with low risk of all conditions. Exactly how this works depends on the customer’s own values - would they prefer an embryo with lower cancer risk to one who will have fewer heart attacks? - and the exact benefits will depend on how parents make that decision. Genomic Prediction and Herasight try to help by providing semi-objective measures of which embryo is overall healthiest according to different conditions’ effects on longevity and patient-rated quality of life. For Genomic Prediction, that’s the “embryo health score” If you selected the single highest-health-score embryo from a set of five, here’s how they’d do: For Herasight, it’s a “polygenic longevity index”. They don’t give exact risk reduction numbers for each disease, saying that it depends too much on a couple’s specific family history, but say that most people gain 1-4 years of healthy life (when I test it on a set of twenty embryos, the the healthiest gets an extra 1.66 years). How much would you pay to give your children an extra 1-4 years of healthy life? This is no longer a hypothetical question. Here are the costs of the companies in this space: Is it worth it? If: You’re already doing IVF
Orion

Orion is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "SLS sends an Orion around the moon". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Orion
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
1. Widely accepted paper claims a polygenic score predicting over 25% of human intelligence: 70% 2. …50% or more: 20% 3. At least one person is known to have had a “designer baby” genetically edited for something other than preventing specific high-risk disease: 10% 4. At least a thousand people have had such babies, and it’s well known where people can go to do it: 5% 5. At least one cloned human baby, survives beyond one day after birth: 10% 6. Average person can check their polygenic IQ score for reasonable fee (doesn’t have to be very good) in 2023: 80% 7. At least one directly glutamatergic antidepressant approved by FDA: 20% 8. At least one directly neurotrophic antidepressant approved by FDA: 20% 9. At least one genuinely novel antipsychotic approved by FDA: 30% 10. MDMA approved for therapeutic use by FDA: 50% 11. Psilocybin approved for general therapeutic use in at least one country: 30% 12. Gary Taubes’ insulin resistance theory of nutrition has significantly more scholarly acceptance than today: 10% 13. Paleo diet is generally considered and recommended by doctors as best weight-loss diet for average person: 30% 14. SpaceX has launched BFR to orbit: 50% 15. SpaceX has launched a man around the moon: 50% 16. SLS sends an Orion around the moon: 30% 17. Someone has landed a man on the moon: 1% 18. SpaceX has landed (not crashed) an object on Mars: 5% 19. At least one frequently-inhabited private space station in orbit: 30%
OROS-MPH

OROS-MPH is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 06, 2022 and July 06, 2022. The archive places it in contexts such as "“OROS-MPH” is Martian for Concerta". It most often appears alongside Concerta, Pelham, Ritalin.

Reference entry
OROS-MPH
Mention count
1
Issue count
1
First seen
July 06, 2022
Last seen
July 06, 2022
July 06, 2022 · Original source
173 kids, mostly Hispanic boys age 7-12, were in a “therapeutic ADHD summer camp” intended to help them learn focusing and attention-directing techniques (style tip: do not call this a “concentration camp”). The kids had two short classes each day, one on vocabulary and one on a grab bag of different subject matters. For the first three weeks, half the kids got Concerta (ie long-acting Ritalin) and the other half didn’t, then they switched for the next three weeks. As an additional test, there was a ten minute period each day when the kids were asked to do math problems as fast as possible. Here are the results:
“OROS-MPH” is Martian for Concerta. The bottom left graph is how many math problems kids completed per minute. Kids on Concerta do math about 50% faster, and this difference is significant. Bottom right is number of classroom rule violations per hour. Kids on Concerta only cause trouble about half as often, and this is significant too. So the Concerta’s clearly doing something, and I think it would be fair to describe that thing as “making kids pay more attention”.
The bottom left graph is how many math problems kids completed per minute. Kids on Concerta do math about 50% faster, and this difference is significant. Bottom right is number of classroom rule violations per hour. Kids on Concerta only cause trouble about half as often, and this is significant too. So the Concerta’s clearly doing something, and I think it would be fair to describe that thing as “making kids pay more attention”.
Oroxylum

Oroxylum is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 24, 2022 and January 24, 2022. The archive places it in contexts such as "I take oroxylum at least 5 times in Q4 2021". It most often appears alongside 538, ACX, AstraZeneca.

Reference entry
Oroxylum
Mention count
1
Issue count
1
First seen
January 24, 2022
Last seen
January 24, 2022
January 24, 2022 · Original source
PERSONAL 54. I am engaged: 60% 55. I am married: 20% 56. [redacted]: 10% 57. [redacted]: 10% 58. [redacted]: 5% 59. [redacted]: 20% 60. There are no appraisal-related complications to the new house purchase: 50% 61. I live in the new house: 95% 62. I live in the top bedroom: 60% 63. I can hear / get annoyed by neighbor TV noise: 40% 64. I'm playing in a D&D campaign: 70% 65. I go on at least one international trip: 60% 66. I spend at least a month living somewhere other than the Bay: 50% 67. I continue my current exercise routine (and get through an entire cycle of it) in Q4 2021: 70% 68. I meditate at least 15 days in Q4 2021: 60% 69. I take oroxylum at least 5 times in Q4 2021: 40% 70. I take some substance I haven't discovered yet at least 5 times in Q4 2021 (testing exempted): 30% 71. I do at least six new biohacking experiments in the next eight months: 40% 72. [redacted]: 30% 73. The Twitter account I check most frequently isn't one of the five I check frequently now: 20% 74. I make/retweet at least 25 tweets between now and 2022: 70%
oseltamavir

oseltamavir is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 17, 2021 and November 17, 2021. The archive places it in contexts such as "azithromycin, oseltamavir, and some vitamins". It most often appears alongside ACE-2 receptor, ACSH, Ahmed et al.

Reference entry
oseltamavir
Mention count
1
Issue count
1
First seen
November 17, 2021
Last seen
November 17, 2021
November 17, 2021 · Original source
…looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. Lopez-Medina et al: Colombian RCT. 200 patients took ivermectin, another 200 took placebo. They originally worried the placebo might taste different than real ivermectin, then solved this by replacing it with a different placebo, which is a pretty high level of conscientiousness. Primary outcome was originally percent of patients whose symptoms worsened by two points, as rated on a complicated symptom scale when a researcher asked them over the phone. Halfway through the study, they realized nobody was worsening that much, so they changed the primary outcome to time until symptoms got better, as measured by the scale. In the ivermectin group, symptoms improved that much after 10 days; in the placebo group, after 12, p = 0.53. By the end of the study, symptoms had improved in 82% of ivermectin users and 79% of controls, also insignificant. 4 patients in the ivermectin group needed to be hospitalized compared to 6 in the placebo group, again insignificant. This study is bigger than most of the other RCTs, and more polished in terms of how many spelling errors, photographs of computer screens, etc, it contains. It was published in JAMA, one of the most prestigious US medical journals, as opposed to the crappy nth-tier journals most of the others have been in. When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. Ivermectin proponents make some good arguments against it. In order to get as big as it did, Lopez-Medina had to compromise on rigor. Its outcome is how people self-score their symptoms on a hokey scale in a phone interview, instead of viral load or PCR results or anything like that. Still, this is basically what we want, right? In the end, we want people to feel better and less sick, not to get good scores on PCR tests. Also, it changed its primary outcome halfway through; isn’t that bad? I think maybe not; the reason we want a preregistered primary outcome is so that you don’t change halfway through to whatever outcome shows the results you want. The researchers in this study did a good job explaining why they changed their outcome, the change makes sense, and their original outcome would also have shown ivermectin not working (albeit less accurately and effectively). I don’t know of any evidence that they knew (or suspected) final results when switching to this new outcome, and it seems like the most reasonable new outcome to switch to. Finally, their original placebo tasted different from ivermectin (though they switched halfway through). This is one of the few studies where I actually care about placebo, because people are self-rating their symptoms. But realistically most of these people don’t know what ivermectin is supposed to taste like. Also, they did a re-analysis and found there was no difference between the people who got the old placebo and the new one. I’m making a big deal of this because ivmmeta.com - the really impressive meta-analysis site I’ve been going off of - puts a special warning letter underneath their discussion of this study, urging us not to trust it. They don’t do this for any of the other ones we’ve addressed so far - not the one by the guy whose other studies were all frauds, not the one where 50% of 21 people had headaches, not the unrandomized one where the groups were completely different before the experiment started, not even the one by the guy accused of crimes against humanity. Only this one. This makes me a lot less charitable to ivmmeta than I would otherwise be; I think it’s hard to choose this particular warning letter strategy out of well-intentioned commitment to truth. They just really don’t like this big study that shows ivermectin doesn’t work. Also, the warning itself irritates me, and includes paragraphs like: RCTs have a fundamental bias against finding an effect for interventions that are widely available — patients that believe they need treatment are more likely to decline participation and take the intervention [Yeh], i.e., RCTs are more likely to enroll low-risk participants that do not need treatment to recover (this does not apply to the typical pharmaceutical trial of a new drug that is otherwise unavailable). This trial was run in a community where ivermectin was available OTC and very widely known and used. Nobody else worries about this, and there are a million biases that non-randomized studies have that would be super-relevant when discussing those, but somehow when they’re pro-ivermectin the site forgets to be this thorough. I think a better pro-ivermectin response to this study is to point out that all the trends support ivermectin. Symptoms took 10 days to resolve in the ivermectin group vs. 12 in placebo; 4 ivermectin patients were hospitalized vs. 6 placebo patients, etc. Just say that this was an unusually noisy trial because of the self-report methodology, and you’re confident that these small differences will add up to significance when you put them into a meta-analysis. Roy et al: We’re back in East India, and back to non-randomized trials. 56 patients were retrospectively examined; some had been given ivermectin + doxycycline, others hydroxychloroquine, other azithromycin, and others symptomatic treatment only. We don’t get any meaningful information about how this worked, but we are told that they did not differ in “clinical well-being reporting onset timing”. Whatever. Chahla et al: The first of many Argentine trials. 110 patients received medium-dose ivermectin; 144 were kept as a control (no placebo). This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc). They checked to see if there were any differences between the groups, and it sure looks like there were (the experimental group had twice as many obese people as the controls), but as per them, these differences were not statistically significant. Note that if this did make a difference, it would presumably make ivermectin look worse, not better. The primary outcome was given as “increase discharge from outpatient care with COVID-19 mild disease”. This favored the treatment; only 2/110 patients in the ivermectin group failed to be discharged, compared to 20 patients in the control group. But, uh, these were at different medical centers. Can’t different medical centers just have different discharge policies? One discharges you as soon as you seem to be getting better, the other waits to really make sure? This is an utterly crap endpoint to do a cluster randomized controlled trial on. If you’re going to do cRCT, which is never a great idea, you should be using some extremely objective endpoint that doctors and clinic administrators can’t possibly affect, like viral load according to some third-party laboratory, using the same third-party laboratory for both clinics. This is such a bad idea that I can’t help worrying I’m missing or misunderstanding something. If not, this is dumb and bad and should be ignored. Mourya et al: We’re back in India. This is a nonrandomized study comparing 50 patients given ivermectin to 50 patients given hydroxychloroquine. No primary outcome was named, but they focus on PCR negativity. Only 6% of patients in the hydroxychloroquine group were negative, compared to 90% of patients in the ivermectin group! On what day did they do the test? Uh, kind of random, and they admit that “in [the hydroxychloroquine group], mean time difference from the date of initiation of treatment and second test was significantly longer (7.24±2.75 days) as compared to 5.22±1.21 days in [the ivermectin group] (p=0.021).” Since they assessed these groups at different times, we shouldn’t draw any conclusions from them getting different results. Except that as far as I can tell this should handicap ivermectin, making it especially impressive that it did better. But also, the ivermectin group was made mostly of people who had been asymptomatic at the beginning (70%), and the hydroxychloroquine group had almost no asymptomatic cases (8%) . They were giving the ivermectin to healthy people and the hydroxychloroquine to sick people! They admit deep in the discussion that this “may be a confounding factor”. So basically they got totally different groups of people, tested them at totally different times, and the two sets of test results differed. So what? So this is why normal people do RCTs instead of whatever the heck this is, that’s what. Loue et al: …this one isn’t going to be an RCT either. Loue tells a story about a cluster of COVID cases at the French nursing home where he works. He asked people if they wanted to try ivermectin; 10 did and 15 didn’t. 1 ivermectin patient died, compared to 5 non-ivermectin patients. The non-ivermectin group looked a bit sicker than the ivermectin group in the inevitable Table 1, though it’s hard to tell. One interesting possible confounder (not mentioned, but I’m imagining it) is that demented patients probably couldn’t consent to ivermectin and ended up in the control group. This is another case of “I’m not going to trust anything that isn’t an RCT”. Merino et al: Another (sigh) non-RCT. Mexico City tried a public health program where if you called a hotline and said you had COVID, they sent you an emergency kit with various useful supplies. One of those supplies was ivermectin tablets. 18,074 people got the kit (and presumably some appreciable fraction took the ivermectin, though there’s no way to prove that). Their control group is people from before they started giving out the kits, people from after they stopped giving out the kits, and people who didn’t want the kits. There are differences in who got COVID early in the epidemic vs. later, and in people who did opt for medical kits vs. didn’t. To correct these, the researchers tried to adjust for confounders, something which - as I keep trying to hammer home again and again - never works. They found that using the kit led to a 75% or so reduction in hospitalization, though they were unable to separate out the ivermectin from the other things in the kit (paracetamol and aspirin), or from the placebo effect of having a kit and feeling like you had already gotten some treatment (if I understand right, the decision to go to the hospital was left entirely to the patient). I think this study is a moderate point in favor of giving people kits in order to prevent hospital overcrowding, but I’m not willing to accept that it tells us much about ivermectin in particular. Faisal et al: This one was published in The Professional Medical Journal (mispelled as “Profesional Medical Journal” in its URL), so you know it’s going to be good! It describes itself as “a cross-sectional study”, but later says it “randomized patients into two groups”, which would make it an RCT - I think they might just be using the term “cross-sectional” different from the standard American usage. A hospital in Pakistan got 50 patients on ivermectin + azithromycin, and another 50 on azithromycin alone. Primary outcome was not mentioned, and the data were presented confusingly, but a typical result is that only 4% of the ivermectin group had symptoms lasting more than 10 days, whereas 16% of the control group did, p < 0.01. They do a really weird thing where they compare how long it took symptoms to resolve between IVM and control groups within each bin. That is, if I’m understanding correctly, they ask “of the people who took between 3-5 days for symptoms to resolve, did they resolve faster for IVM or control?”. This is an utterly bizarre analysis to perform, although it doesn’t affect the fact that their other results still seem to favor ivermectin. Maybe I’m confused about what’s going on here. I’ve mostly been letting people off easy on no placebo, but I as far as I can tell (not very far) this paper seems to be going off whether patients reported continuing to have symptoms to the hospital doing the study, and I think that is potentially susceptible to placebo effects. Additionally, there’s no preregistration, and even though they talk a lot about doing PCR tests they don’t present the results. This is by no means the worst study here but I still think it’s pretty low quality and I don’t trust it. Aref et al: This one is published in the International Journal Of Nanomedicine, even though I’m pretty sure that isn’t a real thing. In this case the “nanomedicine” is a new nasal spray version of ivermectin which is so confusing I cannot for the life of me figure out what dose they are giving these patients. This Egyptian study gives 57 patients intranasal ivermectin plus hydroxychloroquine, azithromycin, oseltamavir, and some vitamins; another 57 patients get all that stuff except the ivermectin. Primary outcome is not stated, but they look at various symptoms, all of which look better in the ivermectin group: 95% of ivermectin patients got negative PCRs at some time point, compared to 75% of controls, p = 0.004. I am pretty suspicious of this study, not least because it comes from Egypt which has an awful reputation for fake studies, and it returns extreme results that I wouldn’t expect even if ivermectin was actually a wonder drug. But I cannot find any particular thing wrong with it, nor did anyone else I looked at, so I will grudgingly let it stand. Krolewiecki et al: Another Argentine study. This one is a real RCT. 30 patients received ivermectin, 15 were the control group (no placebo, again). Primary outcome was difference in viral load on day 5. The trend favored ivermectin but it was not statistically significant, although they were able to make it statistically significant if they looked at a subset of higher-IVM-plasma-concentration patients. They did not find any difference in clinical outcomes. A pro-ivermectin person could point out that in the subgroup with the highest ivermectin concentrations, the drug seemed to work. A skeptic could point out that this is exactly the kind of subgroup slicing that you are not supposed to do without pre-registering it, which I don’t think this team did. I agree with the skeptic. Vallejos et al: Another Argentine study. It’s big (250 people in each arm). It’s an RCT. It tries to define a primary outcome (“Primary outcome: the trial ended when the last patient who was included achieved the end of study visit”), but that’s not what “primary outcome” means, and they don’t offer an alternative. Other outcomes: no difference in PCR on days 3 or 12. Hospitalization is nonsignificantly better in the ivermectin group (14 vs. 21, p = 0.2), but death is nonsigificantly better in the placebo group (3 vs. 4, p = 0.7). This isn’t even the kind of nonsignificant that might contribute to an exciting meta-analysis later. This is just a pure null result. I cannot find any problem with this study, and neither can anyone else I checked. This is the biggest RCT we’ve seen so far, so we should take it seriously. TOGETHER Trial: Speaking of big RCTs… This one hasn’t been published yet. There’s a video of a talk about it, but I am not going to watch it, because it is a video, so I am getting information secondhand from eg here. Apparently, it compares 677 people (!) randomized to ivermectin to 678 people randomized to placebo. 86 ivermectin patients ended up in the hospital compared to 95 placebo patients, p-value not significant. This was a really big professional trial done by bigshot researchers from a major Canadian university, and the medical establishment is taking it much more seriously than any of these others. When it comes out, it will probably get published in a top journal. When discussing Lopez-Medina, I wrote: When people say things like “sure, a lot of small studies show good results for ivermectin, but the bigger and more professional trials don’t”, this is one of the two big professional trials they’re talking about. This is the other one. Not coincidentally, it’s also the other trial that ivmmeta.com has a warning letter underneath telling you to disregard. Their main concern is that instead of truly randomizing patients to ivermectin vs. placebo, they did a time-dependent randomization that meant during some weeks more patients were getting one or the other. This is a problem because the trial takes place in Brazil, where different variants were more common at different times. Here’s their image: On the one hand, I have immense contempt for ivmmeta for letting all those other awful studies pass and then pulling out all the stops to try to nitpick this one. I have no idea if their proposed randomization failure really happened. And no doubt the reason they’re even able to investigate this is that this study is really careful and transparent - most of them don’t tell you anything about their randomization method. I would be shocked if other studies don’t have all these problems and worse. On the other hand, the point isn’t to be fair, it’s to be right. And this is a potential confounder. Not a huge one. But a potential one. I guess all we can do is try to bound the damage. Even if the confounding is 100% real and bad, there’s no way to make this study consistent with the crazy super-pro-ivermectin results of studies like Espitia-Hernandez and Aref. And even if we deny any confounding, we see the same slight pro-ivermectin trend - 86 hospitalizations vs. 95 - that we’ve seen in so many other studies. Nothing is going to make me believe that this isn’t in the top 33% of studies we’ve been looking at, so let’s add it as grist for the meta-analysis (though maybe not quite as much grist as its vast size indicates) and move on, angrily. Buonfrate et al: An Italian RCT. Patients were randomized into low-dose ivermectin (32), placebo (29), or high-dose ivermectin (32). Primary outcome was viral load on day 7. There was no significant difference (average of 2 in ivermectin groups, 2.2 in placebo group). They admit that they failed to reach the planned sample size, but did a calculation to show that even if they had, the trial could not have returned a positive result. Clinically, an average of 2 patients were hospitalized in each of the ivermectin arms, compared to 0 in the placebo arm - which bucks our previously-very-constant pro-ivermectin trend. Mayer et al: Not an RCT. Patients in an Argentine province were offered the opportunity to try ivermectin; 3266 said yes and become the experimental group, 17966 said no and became the control group. There were many obvious differences between the groups, but they all seemed to handicap ivermectin. There was a nonsignificant trend toward less hospitalization and significantly less mortality (1.5% vs. 2.1%, p = 0.03). While looking into this study, I learned the term “immortal time bias”. This means a period in between selection for the study and the beginning of study recording where patient outcomes are not counted. I think the problem here is that if you signed up for the system on Day X, and if you got sick before they could give you ivermectin, you were in the control group. See this Twitter thread, I have not confirmed everything he says. This only hardens my resolve to stay away from non-RCTs. Borody et al: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. The Analysis If we remove all fraudulent and methodologically unsound studies from the table above, we end up with this: Gideon Meyerowitz-Katz, who investigated many of the studies above for fraud, tried a similar exercise. I learned about his halfway through, couldn’t help seeing it briefly, but tried to avoid remembering it or using it when generating mine (also, I did take the result of his fraud investigations into account), so they should be considered not quite independent efforts. His looks like this: He nixed Chowdhury, Babaloba, Ghauri, Faisal, and Aref, but kept Szenta Fonseca, Biber (?), and Mayer. There was correlation of 0.45, which I guess is okay. I asked him about his decision-making, and he listed a combination of serious statistical errors and small red flags adding up. I was pretty uncomfortable with most of these studies myself, so I will err on the side of severity, and remove all studies that either I or Meyerowitz-Katz disliked. We end up with the following short list: We’ve gone from 29 studies to 11, getting rid of 18 along the way. For the record, we eliminated 2/19 for fraud, 1/19 for severe preregistration violations, 10 for methodological problems, and 6 because Meyerowitz-Katz was suspicious of them. …but honestly this table still looks pretty good for ivermectin, doesn’t it? Still lots of big green boxes. Meyerowitz-Katz accuses ivmmeta of cherry-picking what statistic to use for their forest plot. That is, if a study measures ten outcomes, they sometimes take the most pro-ivermectin outcome. Ivmmeta.com counters that they used a consistent and reasonable (if complicated) process for choosing their outcome of focus, that being: If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on. If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used (the next most serious outcome is used — no studies were excluded). For example, in low-risk populations with no mortality, a reduction in mortality with treatment is not possible, however a reduction in hospitalization, for example, is still valuable. Clinical outcome is considered more important than PCR testing status. When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). If only individual symptom data is available, the most serious symptom has priority, for example difficulty breathing or low SpO2 is more important than cough. I’m having trouble judging this, partly because Meyerowitz-Katz says ivmmeta has corrected some earlier mistakes, and partly because there really is some reasonable debate over how to judge studies with lots of complicated endpoints. By this point I had completely forgotten what ivmmeta did, so I independently coded all 11 remaining studies following something in between my best understanding of their procedure and what I considered common sense. The only exception was that when the most severe outcome was measured in something other than patients (ie average number of virus copies per patient), I defaulted to one that was measured in patients instead, to keep everything with the same denominator. My results mostly matched ivmmeta’s, with one or two exceptions that I think are within the scope of argument or related to my minor deviations from their protocol. Placebo vs. ivermectin groups sometimes differed in size, which I’ve adjusted for and rounded off. Probably I’m forgetting some reason I can’t just do simple summary statistics to this, but whatever. It is p = 0.15, not significant. This is maybe unfair, because there aren’t a lot of deaths in the sample, so by focusing on death rather than more common outcomes we’re pointlessly throwing away sample size. What happens if I unprincipledly pick whatever I think the most reasonable outcome to use from each study is? I’ve chosen “most reasonable” as a balance between “is the most severe” and “has a lot of data points”: Now it’s p = 0.04, seemingly significant, but I had to make some unprincipled decisions to get there. I don’t think I specifically replaced negative findings with positive ones, but I can’t prove that even to myself, let alone to you. [UPDATE 5/31/22: A reader writes in to tell me that the t-test I used above is overly simplistic. A Dersimonian-Laird test is more appropriate for meta-analysis, and would have given 0.03 and 0.005 on the first and second analysis, where I got 0.15 and 0.04. This significantly strengthens the apparent benefit of ivermectin from ‘debatable’ to ‘clear’. I discuss some reasons below why I am not convinced by this apparent benefit.] (how come I’m finding a bunch of things on the edge of significance, but the original ivmmeta site found a lot of extremely significant things? Because they combined ratios, such that “one death in placebo, zero in ivermectin” looked like a nigh-infinite benefit for ivermectin, whereas I’m combining raw numbers. Possibly my way is statistically illegitimate for some reason, but I’m just trying to get a rough estimate of how convinced to be) So we are stuck somewhere between “nonsignificant trend in favor” and “maybe-significant trend in favor, after throwing out some best practices”. This is normally where I would compare my results to those of other meta-analyses made by real professionals. But when I look at them, they all include studies later found to be fake, like Elgazzar, and unsurprisingly come up with wildly positive conclusions. There are about six in this category. One of them later revised their results to exclude Elgazzar and still found strong efficacy for ivermectin, but they still included Niaee and some other dubious studies. The only meta-analysis that doesn’t make these mistakes is Popp (a Cochrane review), which is from before Elgazzar was found to be fraudulent, but coincidentally excludes it for other reasons. It also excludes a lot of good studies like Mahmud and Ravakirti because they give patients other things like HCQ and azithromycin - I chose to include them, because I don’t think they either work or have especially bad side effects, so they’re basically placebo - but Cochrane is always harsh like this. They end up with a point estimate where ivermectin cuts mortality by 40% - but say the confidence intervals are too wide to draw any conclusion. I think this basically agrees with my analyses above - the trends really are in ivermectin’s favor, but once you eliminate all the questionable studies there are too few studies left to have enough statistical power to reach significance. Except that everyone is still focusing on deaths and hospitalizations just because they’re flashy. Mahmud et al, which everyone agrees is a great study, found that ivermectin decreased days until clinical recovery, p = 0.003? So what do you do? This is one of the toughest questions in medicine. It comes up again and again. You have some drug. You read some studies. Again and again, more people are surviving (or avoiding complications) when they get the drug. It’s a pattern strong enough to common-sensically notice. But there isn’t an undeniable, unbreachable fortress of evidence. The drug is really safe and doesn’t have a lot of side effects. So do you give it to your patients? Do you take it yourself? Here this question is especially tough, because, uh, if you say anything in favor of ivermectin you will be cast out of civilization and thrown into the circle of social hell reserved for Klan members and 1/6 insurrectionists. All the health officials in the world will shout “horse dewormer!” at you and compare you to Josef Mengele. But good doctors aren’t supposed to care about such things. Your only goal is to save your patient. Nothing else matters. I am telling you that Mahmud et al is a good study and it got p = 0.003 in favor of ivermectin. You can take the blue pill, and stay a decent respectable member of society. Or you can take the horse dewormer pill, and see where you end up. In a second, I’ll tell you my answer. But you won’t always have me to answer questions like this, and it might be morally edifying to observe your thought process in situations like this. So take a second, and meet me on the other side of the next section heading. … … … … … The Synthesis Hopefully you learned something interesting about yourself there. But my answer is: worms! As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc. Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Oxycodone

Oxycodone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 08, 2023 and June 08, 2023. The archive places it in contexts such as "Oxycodone helps pain". It most often appears alongside ACX survey, Adderall, Ambien.

Reference entry
Oxycodone
Mention count
1
Issue count
1
First seen
June 08, 2023
Last seen
June 08, 2023
June 08, 2023 · Original source
Oxycodone helps pain: 1.0
Pabst Blue Ribbon

Pabst Blue Ribbon is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 19, 2023 and April 19, 2023. The archive places it in contexts such as "people who drank Pabst Blue Ribbon because everyone knows that’s what the people who discover things are supposed to discover". It most often appears alongside Amazon, Amazon, Bill Gates.

Reference entry
Pabst Blue Ribbon
Mention count
1
Issue count
1
First seen
April 19, 2023
Last seen
April 19, 2023
April 19, 2023 · Original source
Others have already written about how nonconformists - people who do the valuable service of telling us when the emperor has no clothes - have their valor stolen by fake nonconformists - people who parrot an established narrative corresponding to what everybody knows nonconformism is supposed to sound like. In the same way, hipsters had their valor stolen by fake hipsters - people who drank Pabst Blue Ribbon because everyone knows that’s what the people who discover things are supposed to discover. Still, the real hipsters had been doing a useful service.
PacBio

PacBio is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 03, 2025 and July 03, 2025. The archive places it in contexts such as "Long-read sequencing (PacBio & ONT, not Illumina's synthetic tech) is clearly better"; "PacBio and ONT are almost on the same level as Illumina in terms of cost/genome". It most often appears alongside 23andme, @alextisyoung, Aborigines.

Reference entry
PacBio
Mention count
1
Issue count
1
First seen
July 03, 2025
Last seen
July 03, 2025
July 03, 2025 · Original source
Genomes aren't lists of SNPs, they are mostly repeats and 2x150bp isn't going to get anywhere near close to capturing that variation, no matter how 'deep' you sequence. Long-read sequencing (PacBio & ONT, not Illumina's synthetic tech) is clearly better, and continues to demonstrate that there is massive variation that is easy to see when you have a bunch of 20kbp fragment, while almost impossible when you're just aligning little chunks of text to a 3gbp genome.
So yeah, most consumer WGS is Illumina, and it’s fine if all you want is common SNPs. But I can't wait for human genomics to migrate to long reads and overturn some of the perceived wisdom from two decades of Illumina dominance […] PacBio and ONT are almost on the same level as Illumina in terms of cost/genome, and they ACTUALLY give you the whole genome!
Paint

Paint is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 30, 2020 and August 30, 2020. The archive places it in contexts such as "Download it and check on Paint or Photoshop". It most often appears alongside artificial intelligence, Astral Codex Ten, English.

Reference entry
Paint
Mention count
1
Issue count
1
First seen
August 30, 2020
Last seen
August 30, 2020
August 30, 2020 · Original source
The top and bottom chess sets in this picture are exactly the same color. Download it and check on Paint or Photoshop if you don't believe me. We use "as different as black and white" to mean obviously, undeniably different. But in fact a slightly different context can confuse our brains so completely that we mistake white for black and vice versa. I believe the same laws of thought apply in the frontal lobe as in the visual cortex. The same forces that transform gray chess sets to white or black, outside our conscious control or comprehension, influence how we think about policies, coalitions, and principles, making them appear self-evidently good or viciously evil. I think this is the century where we'll either learn to understand and deal with our cognitive biases, or else all kill each other.
Panadol

Panadol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 13, 2022 and April 13, 2022. The archive places it in contexts such as "Tylenol (aka Panadol, paracetamol, acetaminophen, etc)". It most often appears alongside acetaminophen, ADHD, Arthur Jensen.

Reference entry
Panadol
Mention count
1
Issue count
1
First seen
April 13, 2022
Last seen
April 13, 2022
April 13, 2022 · Original source
Doctors have been gradually chipping away at pregnant women’s ability to use pain medication. First it was “don’t use opioids, your baby could have birth defects”. Then it was “and don’t use ibuprofen, your baby could have kidney problems”. Then it was “and don’t use too much aspirin either, your baby could get cardiovascular problems”. That left Tylenol (aka Panadol, paracetamol, acetaminophen, etc) as the only pregnancy-safe pain reliever. Well, bad news…
Only the sinister foreign “black licorice” contains glycyrrhizin. The red licorice eaten by normal red-blooded Americans is (as per American tradition) made out of corn syrup derivatives with no real licorice whatsoever, and should be fine. Avoid Painkillers, Including Tylenol (Tier 2) Doctors have been gradually chipping away at pregnant women’s ability to use pain medication. First it was “don’t use opioids, your baby could have birth defects”. Then it was “and don’t use ibuprofen, your baby could have kidney problems”. Then it was “and don’t use too much aspirin either, your baby could get cardiovascular problems”. That left Tylenol (aka Panadol, paracetamol, acetaminophen, etc) as the only pregnancy-safe pain reliever. Well, bad news…
Last year, Nature Reviews Endocrinology published Consensus Statement: Paracetamol Use In Pregnancy - A Call For Precautionary Action, by ninety-one leading scientists. It argued that Tylenol use during pregnancy might cause neurodevelopmental and urogenital disorders in children. They argue that Tylenol babies have higher risk of abnormal hormone profiles, abnormal urinary tract development, and ADHD. What’s their evidence?
Panax ginseng

Panax ginseng is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "‘a completely FAKE Panax ginseng as their highest value rating product’". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
Panax ginseng
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
Labdoor is an affiliate marketing site masquerading as an independent testing site. They use flawed methodologies to give misleading data and profit off people clicking on their affiliate links to buy products. They had a completely FAKE Panax ginseng as their highest value rating product for OVER A YEAR after I showed them data proving it was fake. It was American ginseng cut with corn starch, and I provided them the data on it when they put up their ginseng ratings. It took them a whole year to even mention there was an issue, then they quietly just put a small note on the page saying the results were under investigation. They made affiliate commissions that whole time as everyone bought the fake Panax ginseng by clicking on the links on their rating page... It's not just like it was an innocent mistake. I called them out publicly over it, and we discussed it privately vi PM here on Reddit. They could have removed that product page when I alerted them, but it stayed up. Just insane to me.
paracetamol

paracetamol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 01, 2023 and February 01, 2023. The archive places it in contexts such as "The control group (which they seem to think can also be called 'the white group') took zinc, paracetamol, and maybe azithromycin". It most often appears alongside 2006 Ioannidis paper, ACTIV-6, Alexandros.

Reference entry
paracetamol
Mention count
1
Issue count
1
First seen
February 01, 2023
Last seen
February 01, 2023
February 01, 2023 · Original source
Carvallo said that zero people in the treatment group of his study got COVID, compared to 58% of people in the control group. This is a pretty implausibly big effect, even by the standards of other pro-ivermectin studies, although I don’t know if anyone else tried the exact same preventative protocol as Carvallo. I think this is a more nuanced story than Alexandros’ version where Buzzfeed just doesn’t know that sometimes studies happen at more than one hospital. Is fraud the best explanation? I think Alexandros thinks of Carvallo as just not keeping very good records, so he doesn’t have raw data, and probably mixed up his numbers a few times or gave false numbers, and didn’t have anything to send his collaborators when they asked. I think this is maybe possible, although it seems suspicious that he falsely said Dr. Lombardo was involved, falsely claimed the hospital involved was doing a different trial, and got very implausible results. I can imagine weird chains of events that would cause all of these things through honest misunderstandings. But they don’t seem like the best explanation. After discussing this with Alexandros, he objects to my use of the term “known fraudster”. Perhaps I should have said “highly credibly suspected fraudster” instead, although in a Bayesian sense nothing can ever be 100% and at some point plausibility shades imperceptibly into knowledge. Still, I feel like my description here was more accurate than Alexandros’, which just mentions the hospital approval issue and says nothing about any of the rest of this in a thousand word subsection about this study in particular. I did err in saying the Carvallo paper was retracted. According to the article: After BuzzFeed News raised questions about how the study’s data was collected and analyzed, a representative from the Journal of Biomedical Research and Clinical Investigation, which published the results, said late Monday, “We will remove the paper temporarily.” A link was removed from the table of contents — but was reinstated by Thursday. The journal’s explanation, provided after this story was published, was that the author “informed us that he has already provided the evidence of his study to the media.” I apologize for the error. Elalfy et al (still disagree with Alexandros) I described this as: As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable […] There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. In the summary post, Alexandros’ entire criticism of my coverage of this trial, one of the seven trials he focuses on as most unfairly covered and uses as the lynchpin of his argument that I am morally culpable for disastrously bad reporting, is: [Elalfy et al] are accused of incompetence for failing to randomize their groups multiple times in Scott’s piece. The paper writes in six separate places that it is not reporting on a randomized trial, amongst them on a diagram that Scott included in his own essay. Hard to imagine how else they could have made it clear. In his full post on this, he goes line by line to point out all the places they say they are non-randomized, pausing to snark about how dumb I am for not noticing each time4. But he never addresses the actual source of my confusion, which is the part of the paper where it says that: Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment. If this was done as described, it should be an (almost) random trial; patients who come in on Wednesdays shouldn’t systematically differ from patients who come in on Thursdays5. But in fact, it looks (assuming I am understanding a very ambiguous table correctly) like there are very large pre-existing differences between the groups, sufficient to explain the entire result. If they in fact followed their days-of-the-week protocol, and it was random as expected, then I’m misunderstanding the table seeming to show very large differences, and they have indeed found evidence for ivermectin’s efficacy. If they didn’t follow their day-of-the-week protocol and it’s non-random, then maybe I’m understanding the table correctly and their groups had large differences to begin with and the fact that they had large differences at the end of the trial doesn’t demonstrate anything about ivermectin. This is all I was trying to say in the post, and instead of having any opinion on it Alexandros just makes fun of me for saying it. I think our actual crux is that Alexandros thinks a table of big differences between the groups has to be post-treatment (based on how big the differences are), whereas I’m not sure (because it’s unclear in the study, and also because the authors describe what could be a randomization method but also go on and on about how nonrandom they are). This is why I thought it mattered how random it was! Maybe instead of mocking me for this, you can admit it’s an important and relevant question! Ghauri et al (still disagree with Alexandros) I describe this as: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. Alexandros notes that these are three differences between experimental/control groups, out of 33 listed characteristics that could have been different. There is approximately a 23% chance (he calculates) that you could get these differences by chance. He accuses me of failing to do a formal Carlisle test - the usual test you would use to determine whether weird differences between randomized groups are because of fraud - instead eyeballing it and getting it wrong. Here I do want to defend myself: I am not accusing Ghauri et al of fraud. In fact, this would be nonsensical: they admit they are assigning patients nonrandomly. Carlisle tests are usually done to show that something about group assignment is impossible (and therefore fraudulent) in a fair random assignment. But these people aren’t claiming to have done a fair random assignment, so I’m not sure what a Carlisle test would prove. My argument is more like: this is nonrandom, therefore we should expect it to be unfair. It is unnecessary, but helpful, to note an actual apparent unfairness - there’s some evidence they gave the ivermectin to less severe patients (as measured by corticosteroid use). Therefore, we can’t necessarily trust this to be a fair trial (which it was never really claiming to be). In the end I kept Ghauri as an okay study, although GMK didn’t so it ended out trashed in the final analysis anyway. I think my thinking was that I never claimed to be only looking at RCTs, so this non-RCT whose between-group-differences confirmed that it was indeed a non-RCT with all the risk of bias that entails, didn’t necessarily need to be ruled out. Still, I don’t think I was wrong to mention this possibility, and I think Alexandros was wrong to suggest that I needed to do extra tests for this to be fair. Borody et al (still disagree with Alexandros) I described this as: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. Alexandros lists his full concerns here. My summary: Scott is being incredibly disrespectful to the authors, who are in fact a legendary gastroenterologist who invented life-saving h. pylori therapy and a brilliant immunologist who invented a well-regarded bronchitis vaccine (in particular, in describing their control group, I said “this is not how you control group, @#!% you”.
Parti-20B

Parti-20B is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2022 and June 27, 2022. The archive places it in contexts such as "does anyone reading this have access to the new Parti-20B image model from Google?". It most often appears alongside ACX Podcast, Astralcodexten Com, Cameron Bucker.

Reference entry
Parti-20B
Mention count
1
Issue count
1
First seen
June 27, 2022
Last seen
June 27, 2022
June 27, 2022 · Original source
3: Related: does anyone reading this have access to the new Parti-20B image model from Google? I would like to check whether I have won my bet with Vitor about image model progress. If yes, I will write a post about it and give you good publicity. Please contact me at scott[at]slatestarcodex[dot]com
Partyr

Partyr is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 04, 2022 and May 04, 2022. The archive places it in contexts such as "I’m trying Partyr. It’s a new all-in-one party-throwing service". It most often appears alongside 1000, 1200, 1400.

Reference entry
Partyr
Mention count
1
Issue count
1
First seen
May 04, 2022
Last seen
May 04, 2022
May 04, 2022 · Original source
“I don’t!” he shouts back. “I’m trying Partyr. It’s a new all-in-one party-throwing service. You give them an address, a time, and an ideal number of guests, pick from one of their preset themes, and they make everything happen.”
“If needed! The idea is, you have some friends you want to impress by throwing a big party. But you don’t know how many of them will come. And you don’t want only two or three people to come, and then it’s really embarrassing. So you set an ideal number of people to come to the party. Then you see how many people RSVPed, and if it’s less than your ideal Partyr sends you enough guests to make up the difference.”
“How many of the people here tonight are paid Partyr guests?”
Patagonia

Patagonia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 13, 2025 and March 13, 2025. The archive places it in contexts such as "Outdoorwear company Patagonia is a typical example". It most often appears alongside ACLU, AI Lab Watch, Altman.

Reference entry
Patagonia
Mention count
1
Issue count
1
First seen
March 13, 2025
Last seen
March 13, 2025
March 13, 2025 · Original source
It’s neither unusual nor illegal for nonprofits to own forprofits. Outdoorwear company Patagonia is a typical example. Its billionaire founder gave his shares to a purpose-designed environmentalist trust. They run Patagonia in an environmentally friendly way and spend the profits on environmental protection. In theory, OpenAI could do something similar.
PE

PE is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "no bacopa is entirely trustworthy, but at least ND and PE are better than Swanson". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
PE
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
Regarding the overages, I agree that it’s better to penalize something more for an underage than an overage, but I am still not sure this is good communication. Consider for example their bacopa rankings. Just looking at this, I would come away with the conclusion “no bacopa is entirely trustworthy, but at least ND and PE are better than Swanson”. But if I’m understanding right, the whole ranking is entirely driven by overages, and nobody (including the brand getting a C-) has any other problem. I suppose it’s fair to, if everything is exactly the same, rank based on a minor issue, but I think if I didn’t understand what was going on here I would be much more concerned about Swanson than justified.
PearConnect

PearConnect is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 12, 2021 and May 12, 2021. The archive places it in contexts such as "Our support team, PearConnect™, will help determine insurance coverage eligibility". It most often appears alongside Alexander Pope, CBT-i, Cognitive Behavioral Therapy For Insomnia.

Reference entry
PearConnect
Mention count
1
Issue count
1
First seen
May 12, 2021
Last seen
May 12, 2021
May 12, 2021 · Original source
You or I could create a CBT-i app tomorrow and sell it for $1 or $10 or whatever the normal price of an app is. But it wouldn’t be official, and insurance companies wouldn’t pay for it. Pear Therapeutics created a CBT-i app, put in the work to make it official, and now they’re selling it for $899. “Our support team, PearConnect™, will help determine insurance coverage eligibility during onboarding”, says their website.
People’s Pint

People’s Pint is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 26, 2022 and August 26, 2022. The archive places it in contexts such as "iPad that has a People’s Pint sticker". It most often appears alongside 't Heem, 10/40 Coffee, 11841 Wagner St., Culver City.

Reference entry
People’s Pint
Mention count
1
Issue count
1
First seen
August 26, 2022
Last seen
August 26, 2022
August 26, 2022 · Original source
HUNTSVILLE, AL Contact: Mike, mjhouse[at]protonmail[dot]com Time: Saturday, September 3, 3:00 PM Location: Barnes & Noble – 300 The Bridge St #100, Huntsville, AL 35806. I'll be in the cafe with a sign that says ACX MEETUP on it. Coordinates: 866MP88H+53 Event link(s): LessWrong Notes: Barnes & Noble has an area for little kids. If you want to bring a service animal, that's probably fine, but I doubt they allow pets. PHOENIX, AZ Contact: Ben Morin, benjamin[dot]j[dot]morin[at]gmail[dot]com Time: Saturday, October 15, 1:00 PM Location: Thirsty Lion Pub in Tempe. I will have a table with an ACX sign. Coordinates: 8559FVVQ+6C Event link(s): LessWrong Group info: This will be our 5th meetup (started during the meetups everywhere last year). Notes: Please email if interested to be added to the email list, even if you can't make this event BELMONT, CA Contact: Moshe Z., belmont-acx[at]devskillup[dot]com Time: Sunday, September 4, 2:00 PM Location: Twin Pines Park, Picnic Tables. The table will have some sign saying 'ACX Meetup' on it. Coordinates: 849VGP8C+RRG Event link(s): LessWrong Group info: You can join the mailing list here. BERKELEY, CA Contact: Scott Time: Sunday, September 18, 1:00 PM Location: Rose Garden Inn, a rationalist event space at 2740 Telegraph Ave. Come in through the front gate on Telegraph. Coordinates: 849VVP5R+X7V Event link(s): LessWrong Group info: The Bay rationality community has a mailing list, a Discord server, and a Facebook group. There are dinner meetups every Thursday at 7 PM in the East Bay, and occasional meetups in SF and South Bay. FILLMORE, CA Contact: Ryan, wiserd[at]gmail[dot]com, Discord: Wiserd#0906 Time: Saturday, October 1st, 6:00 PM Location: It's my house. There are a bunch of plants on the porch and garbage bins in the driveway. Coordinates: 856393VX+VQ Event link(s): LessWrong Notes: Please RSVP to my email or Discord. Kids and dogs are welcome in the back yard. Full vaccinations (on the honor system) and masks required. GRASS VALLEY, CA Contact: Max Harms, raelifin[at]gmail[dot]com Time: Saturday, September 10, 2:00 PM Location: Condon Park by the prospector statue. In the case of rain we'll change the location to a residence, so RSVP to get updated! Coordinates: 84FW6W8H+C5 Event link(s): LessWrong IRVINE, CA Contact: Nick C, cohenskijanuary1[at]mail[dot]com Time: Saturday, October 1, 2:00 PM Location: University Town Center Coordinates: 8554M526+7H Event link(s): LessWrong Group info: We meet once a month at the same location. LOS ANGELES, CA Contact: Vishal Prasad (koreindian), vprasadcs[at]gmail[dot]com, Contact me on Discord. I am "Vishal" on the server. Time: Saturday, October 8, 6:30 PM Location: 11841 Wagner St., Culver City, CA 90039 Coordinates: 8553XHWM+GP Event link(s): LessWrong Group info: We meet weekly every Wednesday. We have been around for over 8 years. We discuss articles, watch movies, lift weights. We have a Discord server, a LessWrong group, and a website! Notes: Please RSVP on LessWrong so I know how much food to get. NEWPORT BEACH, CA Contact: Michael M, michaelmichalchik[at]gmail[dot]com Time: Saturday, August 27, 2:00 PM Location: Picnic tables next to 1900 Port Carlow community clubhouse. The park is verdant and pleasant and easy to access. Free street parking nearby. In case of bad weather, we have a couple of near by places to relocate to. Coordinates: 8554J48R+WCX Event link(s): LessWrong, Facebook event Group info: We will meet most Saturdays at 2pm until whenever. There will be short suggested readings and question most weeks to spur conversation, but they are optional. Each week we will ask if people have had something happen recently that surprised them or changed the way they looked at the world. Something that should or did update their priors. Participation is optional. Notes: Its a public park with tables and BBQ's so you can bring food and well behaved pets. We may regularly go on casual walks in the surrounding area. SAN DIEGO, CA Contact: Julius, julius[dot]simonelli[at]gmail[dot]com Time: Sunday, October 9, 3:00 PM Location: We will meet up in Bird Park. I will be wearing a red shirt. Coordinates: 8544PVQ8+Q7 Event link(s): LessWrong, Meetup.com Group info: Join our Discord server SAN FRANCISCO, CA Contact: Derek Pankaew, derekpankaew[at]gmail[dot]com Time: Sunday, September 18, 11:00 AM Location: We'll between in the Panhandle, between Ashbury and Masonic, with a 'ACX' sign. Coordinates: 849VQHC3+V8 Event link(s): LessWrong SAN JOSE, CA Contact: David Friedman, ddfr[at]daviddfriedman[dot]com Time: Saturday, September 17, 2:00 PM Location: 3806 Williams Rd, San Jose, CA 95117 Coordinates: 849W825J+6P Event link(s): LessWrong Group info: Before Covid we hosted every month or two. No structure, just conversation and food. We feed everyone who is still there at dinner time. We have done it once or twice since Covid. I have an email list of interested people. Notes: Kids are welcome. Please RSVP to my email so I will have a rough count of how many we are feeding. SAN MARCOS, CA Contact: Eric F., EricF14159[at]gmail[dot]com Time: Sunday, September 25, 2:00 PM Location: Hollandia Park Soccer Field. At the tables near the top parking lot. Coordinates: 85544VW4+RV Event link(s): LessWrong BOULDER, CO Contact: Josh Sacks, josh[dot]sacks+acx[at]gmail[dot]com Time: Sunday, October 16, 3:00 PM Location: 9191 Tahoe Ln, Boulder, CO 80301 Coordinates: 85GP2V96+JQ Event link(s): LessWrong Notes: Please RSVP on LessWrong so we know ~ how many people to expect! CARBONDALE, CO Contact: Nick, naj[at]njarboe[dot]com Time: Saturday, September 3, 1:00 PM Location: Sopris Park - Center covered picnic tables - blue shirt with ACX sign on table Coordinates: 85FJ9QXP+QMF Event link(s): LessWrong DENVER, CO Contact: Ian Philips, iansphilips[at]gmail[dot]com, Discord: palebone#2796 Time: Sunday, October 2, 11:00 AM Location: We'll be in the backyard patio of St. Mark's Coffee House. I'll wear a white shirt with (my brothers') baby faces on it and have a brown hat on. Coordinates: 85FQP2VP+9R Event link(s): LessWrong Group info: We meet typically 4 times a year. LAKEWOOD, CO Contact: Steven Zuber, stevenjzuber[at]gmail[dot]com Time: Wednesday, October 5, 7:00 PM Location: We meet in the clubhouse located in this townhome community: 8769 W Cornell Ave Lakewood, CO 80227 Coordinates: 85FPMW64+MW Event link(s): LessWrong, Meetup.com Group info: We meet the first Wednesday of every month. Informal, casual atmosphere with occasional presentations by people. Notes: Check the Meetup page or Facebook group for updates. FAIRFIELD, CT Contact: Justin Barclay, barclay[dot]justin[at]gmail[dot]com Time: Saturday, September 10, 10:00 AM Location: South Pine Creek Beach. I'll set up near the lifeguard stand. Coordinates: 87H84PCH+CM Event link(s): LessWrong MANCHESTER, CT Contact: Mike, park-mike[at]outlook[dot]com Time: Saturday, September 17, 5:00 PM Location: Near flagpole on top of hill Coordinates: 87H9QFFH+J7 Event link(s): LessWrong NEW HAVEN, CT Contact: RM, acx[dot]meetup[dot]nhv[at]gmail[dot]com Time: Sunday, September 18, 12:30 PM Location: Cross Campus (Yale University), New Haven, CT 06511. We'll be on the grass on the northern half of Cross Campus, closest to Sterling Memorial Library. I'll be wearing an orange shirt. Coordinates: 87H9836C+8VG Event link(s): LessWrong Notes: Feel free to bring friends! The vibe will be welcoming and relaxed, and you can stay for any amount of time. Please email me if you're thinking about coming so I can get the right number of Insomnia cookies! WASHINGTON, DC Contact: John Bennett, WashingtonDCAstralCodexTen[at]gmail[dot]com Time: Saturday, September 17, 6:00 PM Location: Froggy Bottom Pub: 2021 K Street NW, Washington, D.C. 20006 Coordinates: 87C4WX33+3J Event link(s): LessWrong, Facebook event Group info: The Washington DC ACX/SSC group has been active since the first Meetups Everywhere in 2017. We have Monthly Socials downtown, hikes, board game days, and other cultural events. We're looking to spin up more rationality Dojo-type events with nearby groups in the coming months. Notes: We've rented out the Froggy Bottom Pub for the night, dinner and soft drinks will be provided. Alcohol available for purchase if desired, but no purchases are required. Metered street parking on nearby blocks is free after 6:30. Closest Metros are Farragut West and Farragut North. CAPE CORAL / FORT MYERS, FL Contact: Shawn Spilman, shawn[dot]spilman[at]outlook[dot]com, 508 655 8123 Time: Sunday, October 2, 1:00 PM Location: 929 SW 54th Ln, Cape Coral, FL 33914 Coordinates: 76RWH224+44 Event link(s): LessWrong Notes: RSVP via email. I can be flexible about the date. GULF BREEZE / PENSACOLA, FL Contact: Christian, christian[dot]h[dot]williams[at]gmail[dot]com Time: Wednesday, October 12, 7:30 PM Location: The Bridge Bar - 33 Gulf Breeze Pkwy A, Gulf Breeze, FL 32561 Coordinates: 862J9RCF+G6 Event link(s): LessWrong Notes: Please RSVP by emailing me. Thanks! If I don't hear from anyone, I won't be there. I work for Metaculus, but promise not to talk your ear off about forecasting. (Unless you want it talked off.) MIAMI, FL Contact: Eric Magro, eric135033[at]gmail[dot]com, Discord: eric135#4943 Time: Sunday, September 11, 5:00 PM Location: Buckminster Fuller Fly's Eye Dome 140 NE 39th St #001, Miami, FL 33137 ----- Look for a paper sign on a table that says ACX MEETUP west of the dome. Coordinates: 76QXRR65+V2 Event link(s): LessWrong Group info: Miami ACX started in 2017. Our official meetup happens monthly in either Miami or Broward. There are activities happening on a weekly basis from Miami to Palm Beach. We have a Facebook group, Discord server, and Meetup.com group. ORLANDO, FL Contact: Noah Topper, noah[dot]topper[at]gmail[dot]com Time: Friday, September 16, 7:00 PM Location: 4000 Central Florida Blvd, Orlando, FL. We'll be meeting up at UCF's pavilion near Garages A and I. I'll have a pretty ACX Meetup sign. Coordinates: 76WWJQ2X+82 Event link(s): LessWrong Group info: We try to meet up once a month, so far they've just been casual social meetups with natural discussions of rationality topics. Here's our Discord link :) Notes: RSVPs on LessWrong would be greatly appreciated. :) TALLAHASSEE, FL Contact: JF, jf19o[at]fsu[dot]edu Time: Monday, August 29, 2:00 PM Location: Landis, FSU. I will be wearing a black shirt Coordinates: 862QCPR3+PX Event link(s): LessWrong ATHENS, GA Contact: Dallon, knox[dot]dallon[dot]a[at]gmail[dot]com, Discord: leonard#4208 Time: Saturday, October 15, 3:00 PM Location: Hendershots on Prince Avenue Coordinates: 865RXJ68+2W Event link(s): LessWrong Notes: I might bring some board games ATLANTA, GA Contact: Steve French, steve[at]digitaltoolfactory[dot]net Time: Saturday, September 17, 2:00 PM Location: Bold Monk Brewing - 1737 Ellsworth Industrial Blvd NW suite d-1 · Atlanta, GA (upstairs – look for the ACX Atlanta sign) Coordinates: 865QRH2F+V8 Event link(s): LessWrong, Meetup.com Group info: We've been in existence for four years – we have a dedicated crew and a very active Slack group Notes: Please RSVP on LessWrong or Meetup.com HONOLULU, HI Contact: Matt Popovich, mattpopovich[at]outlook[dot]com Time: Saturday, September 3, 4:00 PM Location: We'll meet at Magic Island at Ala Moana Beach Park, 1201 Ala Moana Blvd, Honolulu, HI 96814. From the parking lot, walk along the left side of the peninsula out toward Magic Island Lagoon. We're usually near the end of the peninsula, somewhere around the bathroom building. Look for the large 'ACX' sign. Coordinates: 73H475M3+JP Event link(s): LessWrong, Meetup.com Group info: Honolulu Rationality hosts discussion meetups about twice a month in Ala Moana Beach Park. Check us out on our website BOISE, ID Contact: Julia and John, jae[dot]miomu[at]gmail[dot]com Time: Friday, October 7, 6:00 PM Location: Old Timer's Shelter in Ann Morrison Park. I will have an ACX sign. Coordinates: 85M5JQ6P+96 Event link(s): LessWrong Notes: Please RSVP and feel free to bring kids. CHAMPAIGN-URBANA, IL Contact: Ben, cu[dot]acx[dot]meetups[at]gmail[dot]com Time: Friday, September 9, 7:00 PM Location: Siebel Center for Computer Science, Room 4403 Coordinates: 86GH4Q7G+H8F Event link(s): LessWrong Group info: Discord server Notes: RSVPs are appreciated but not at all required. You can RSVP by email or by pinging me in the Discord server. Suggested entrance is the East side of the building (see Coordinates) - we'll try to make sure at least that door is unlocked, but if it isn't then ping us on email or Discord. CHICAGO, IL Contact: Todd, info[at]chicagorationality[dot]com, https://chicagorationality.com/ Time: Sunday, September 18, 1:00 PM Location: Grant Park - North side of Balbo between the tracks and Columbus Coordinates: 86HJV9FH+84 Event link(s): LessWrong Group info: Chicago Rationality does a monthly discussion meetup (typically the first Saturday of the month) and a monthly social meetup (typically the third weekend of the month) Notes: Sign up for our email list to be notified of future meetups EVANSTON, IL Contact: Uzair, uzairq93[at]gmail[dot]com Time: Saturday, October 1, 7:00 PM Location: 626 Church Street, Evanston IL 60201 Coordinates: 86JJ28X9+5WQ Event link(s): LessWrong Notes: The venue is a pub but it's really more of a restaurant, big long tables available so space should be fine and non drinkers shouldn't feel too out of place. BLOOMINGTON, IN Contact: Avery, acxbloomington[at]fastmail[dot]com Time: Sunday, October 16, 2:00 PM Location: Switchyard Park. Will be at one of the tables near the Rogers Street parking lot. I will bring a cardboard sign that says “ACX”. Coordinates: 86FM4FX6+4Q Event link(s): LessWrong Group info: We met last year for Meetups Everywhere and it was fun! Here's a link to our Discord. Notes: You can RSVP via Discord or email, but you are encouraged to show up even if you did not RSVP! WEST LAFAYETTE, IN Contact: NR, mapreader4[at]gmail[dot]com Time: Saturday, September 17, 1:00 PM Location: 1275 1st Street, West Lafayette, IN 47906. We'll be in the south of the Earhart Hall lobby (not the dining court) near the piano, and I will be wearing a green shirt and carrying a sign with ACX MEETUP on it. Coordinates: 86GMC3GG+728 Event link(s): LessWrong LEXINGTON, KY Contact: Nathan, nwculley[at]gmail[dot]com Time: Saturday, September 3, 7:00 PM Location: Blue Stallion Brewing. 610 W. 3rd St., Lexington, KY 40508. We will have a sign indicating we are the ACX meetup. Coordinates: 86CQ3F4X+VF Event link(s): LessWrong Group info: We meet 1-2 times a month to talk about ACX, books, memes, etc., often over drinks and board games. NEW ORLEANS, LA Contact: Blake, blake[at]philosophers[dot]group Time: Sunday, September 4, 11:11 AM Location: Petite Clouet Cafe. Look for the group with an iPad that has a People’s Pint sticker. Coordinates: 76XFXX73+8R Event link(s): LessWrong Group info: Website Notes: Hybrid in-person and online, video link sent weekly. Email for the link. BOSTON, MA Contact: Robi Rahman, robirahman94[at]gmail[dot]com, 7039818526 Time: Saturday, September 10, 5:00 PM Location: Boston Common, at the Parkman Bandstand gazebo Coordinates: 87JC9W3M+PR Event link(s): LessWrong, Facebook event Group info: Mailing list, Facebook group, Meetup.com Notes: We'll be providing food at the meetup, and giving out free books related to ACX, rationality, and effective altruism. Email the hosts if you'd like a particular book or you have any dietary restrictions. Our group is also doing a tour of the JFK Presidential Library on September 9, you’re welcome to join! NORTHAMPTON, MA Contact: Alex, alex[at]alexliebowitz[dot]com Time: Friday, September 9, 6:00 PM Location: The Deck, 125A Pleasant St., Northampton MA 01096. The official address is bizarre and inaccurate; it's the outdoor dining part of a group of bars & restaurants in a former rail station... a whole block away from Pleasant St. The simplest way to get to The Deck is to enter The Platform, one of the other restaurants, by its street entrance around 36 Strong Ave., here (make sure to look at street view). Go inside and ask them to show you to The Deck. We'll have a sign. Coordinates: 87J9899F+H7H Event link(s): LessWrong, Facebook event Group info: We started in the 2018 Meetups Everywhere and is still going strong. We aim to meet about once every two weeks. At most meetups we get about 5-7 people out of a rotation of 15-20; Meetups Everywhere and other special events tend to bring in a few more than usual. We're a totally social meetup with no 'format' or suggested readings. Although it's not rare for us to touch on ACX articles and related topics, the conversation varies wildly, and you are welcome even if you're the most occasional ACX reader. Notes: We have a (not very active) Discord where you can DM me or post on a public channel. I'm most responsive by email. There is a small chance we'll have to change the location to somewhere else in Northampton. Please check the Less Wrong or Facebook posts on or after August 26 to get the final word on location. BALTIMORE, MD Contact: Rivka, rivka[at]adrusi[dot]com Time: Sunday, September 11, 7:00 PM Location: UMBC outside of the Performing Arts and Humanities Building, on the north side. I will have a sign that says ACX meetup. Parking is free on the weekends. Edit: Rain is forecasted; if it’s raining, we will be inside of the Performing Arts building, on the ground floor just inside the entrance. Coordinates: 87F5774P+53 Event link(s): LessWrong Group info: We meet Sundays at 7pm — half are in person and half are virtual. Notes: There will be pizza and drinks DETROIT, MI Contact: Matt Arnold, matt[dot]mattarn[at]gmail[dot]com Time: Tuesday, September 20, 7:00 PM Location: Tenacity Craft, 8517 2nd Ave, Detroit, MI 48202 Coordinates: 86JR9WG9+R6 Event link(s): LessWrong MINNEAPOLIS, MN Contact: Timothy, tmbond[at]gmail[dot]com Time: Saturday, September 10, 1:00 PM Location: Meet at the picnic tables near the southeast corner of Powderhorn Park - the ones by the parking lot. I will be wearing a green Google t-shirt and have a sign that says ACX. Coordinates: 86P8WPRW+76 Event link(s): LessWrong Notes: I will bring some snacks (but not a full lunch, so eat before or bring something if you'll be that hungry). Please RSVP on LessWrong. KANSAS CITY, MO Contact: Alex, alex[dot]hedtke[at]gmail[dot]com Time: Friday, September 16, 6:30 PM Location: We will be in the courtyard above Whole Foods (which is also an apartment complex). You can enter through the apartment lobby, located on Oak Street. We will have runners shepherding people from the entrance up to the courtyard. Coordinates: 86F72CM8+RR Event link(s): LessWrong, Meetup.com SAINT LOUIS, MO Contact: JohnBuridan, littlejohnburidan[at]gmail[dot]com Time: Saturday, October 8, 1:00 PM Location: Lily Pond Shelter, Tower Grove Park, St. Louis Coordinates: 86CFJP4R+XV Event link(s): LessWrong Notes: BYOB WEST PLAINS, MO Contact: Liam, liamhession[at]gmail[dot]com Time: Saturday, September 17, 12:00 PM Location: 10/40 Coffee, 24 Court Square, West Plains, MO Coordinates: 868CP4HW+CV Event link(s): LessWrong Notes: Hoping to get anyone from around the Ozark region DURHAM, NC Contact: Will Jarvis, willdjarvis[at]gmail[dot]com Time: Thursday, September 8, 7:30 PM Location: Ponysaurus Brewing Company, 219 Hood St, Durham Coordinates: 8773X4Q3+QW Event link(s): LessWrong Group info: We meet weekly! We also have a Discord LAKEWOOD, NJ Contact: Ben L, mywebdev3[at]gmail[dot]com Time: Saturday, October 29, 8:30 PM Location: TBD Event link(s): LessWrong MORRISTOWN, NJ Contact: Matt, matt[dot]brooks[at]impactmarkets[dot]io, Discord: Matt B#0216 Time: Saturday, October 1, 2:00 PM Location: 10 N Park Pl, Morristown, NJ 07960 (at the center of the Morristown Green) Coordinates: 87G7QGW9+RJ Event link(s): LessWrong Group info: This is the first meetup, come be a founding member of the Northern NJ ACX/EA/LW group! PRINCETON, NJ Contact: Danny K, dskumpf[at]gmail[dot]com Time: Saturday, October 1, 3:00 PM Location: Palmer Square, Princeton, NJ 08540. On the green right outside The Bent Spoon and Rojo's Roastary, near the big tree. I'll have some sort of ACX Meetup sign! Coordinates: 87G7982Q+2CP Event link(s): LessWrong LAS VEGAS, NV Contact: Jonathan Ray, ray[dot]jonathan[dot]w[at]gmail[dot]com Time: Sunday, September 11, 11:45 AM Location: At El Segundo Sol restaurant with giant ACX MEETUP signs Coordinates: 85864RHJ+3H Event link(s): LessWrong, Facebook event Group info: We meet regularly and mostly just socialize. We have a new Discord server. RENO, NV Contact: Steven, stevenl451[at]gmail[dot]com, Discord: Steeven#7407 Time: Friday, September 2, 5:30 PM Location: We'll be in Crissie Caughlin Park, near the tables and the swing set Coordinates: 85F2G46W+FG Event link(s): LessWrong Notes: Feel free to bring kids/dogs and please RSVP on LessWrong if you are going BUFFALO, NY Contact: George Herold, ggherold[at]gmail[dot]com Time: Sunday, September 11, 1:00 PM Location: 932 Welch Rd. Java Center, NY 14082 Coordinates: 87J3W467+8P Notes: Last-minute location change! LONG ISLAND, NY Contact: Gabe, gabeaweil[at]gmail[dot]com Time: Thursday, October 27, 7:00 PM Location: Whales Tale in Northport Coordinates: 87G8VJRW+99 Event link(s): LessWrong NEW YORK CITY, NY Contact: Jasmine, jasminermj[at]gmail[dot]com Time: Sunday, September 11, 4:00 PM Location: Pavillion @ Rockefeller Park, Warren St / River Terrace Coordinates: 87G7PX9M+4J3 Event link(s): LessWrong Group info: OBNYC has a Discord and a Google Group; the Google Group is the main mailing list we use for events NEWBURGH, NY Contact: Pedro David Bonilla, proportionatetoevidence[at]gmail[dot]com, Cell 8452001681 Time: Saturday, September 24, 10:00 AM Location: Perkins Restaurant & Bakery, 1421 NY-300, Newburgh, NY 12550 Coordinates: 87H7GWCH+GF Event link(s): LessWrong ROCHESTER, NY Contact: Skivverus, skivverus[at]gmail[dot]com, Discord: Skivverus#5915 Time: Saturday, October 8, 1:00 PM Location: 4870 Culver Road; will be wearing a polo shirt, jeans, and glasses, and may or may not have figured out a sign due to just getting back from honeymoon. Look for a pair of parrots, one white, one green with a yellow/orange head. Coordinates: 87M46FM6+Q5P Event link(s): LessWrong Notes: Venue very near amusement park; non-bathroom, non-parking amenities are therefore available but not free. Plan accordingly. Not particularly attached to specific location named, just happen to live reasonably close to there; alternative suggestions acceptable. Canadian visitors also welcome should your logistics permit; airport transportation available. RSVP via Discord preferred, but email will also work. CLEVELAND, OH Contact: Jack Zhang, LukeZhao9[at]protonmail[dot]com Time: Saturday, September 24, 1:00 PM Location: Picnic tables at Wade Oval (university circle) Coordinates: 86HWG96Q+GC5 Event link(s): LessWrong COLUMBUS, OH Contact: Daniel, daniel[dot]m[dot]adamiak[at]gmail[dot]com Time: Saturday, September 17, 3:00 PM Location: Jeffrey Park - Clinton Shelter. I will be wearing a red shirt. Coordinates: 86FVX3C3+QF Event link(s): LessWrong Group info: We meet once a month. We discuss EA, AI and other two letter initialisms. Occasionally we go for walks in local grottos and nature trails. Notes: Email me if you want to be added to the mailing list to receive any updates or future invites. RSVPing is appreciated. TOLEDO, OH Contact: Scout, scout[dot]sivar[at]gmail[dot]com Time: Saturday, September 10, 12:00 PM Location: Black Kite Coffee Coordinates: 86HRMCCV+9R Event link(s): LessWrong OKLAHOMA CITY, OK Contact: bean, battleshipbean[at]gmail[dot]com Time: Sunday, October 9, 1:00 PM Location: Edmond Public Library/Shannon Miller Park. I will be wearing a hat that says USS Iowa on it. Coordinates: 8674MG3C+MW Event link(s): LessWrong Group info: Had four people last year and a good time, moved to Edmond because a lot of us are up here. ALBANY, OR Contact: Kenan (he/him), kbitikofer[at]gmail[dot]com Time: Saturday, October 1, 2:00 PM Location: Bowman Park, Albany, Oregon. In or near the shelter. I will wear a bright red shirt and carry a sign with ACX MEETUP on it. Coordinates: 84PRJWR7+XC6 Event link(s): LessWrong CORVALLIS, OR Contact: Ethan Ashkie, ethanashkie[at]gmail[dot]com Time: Wednesday, September 7, 6:00 PM Location: Common Fields, in the reserved outdoor seating near the entrance Coordinates: 84PRHP5P+VQ Event link(s): LessWrong EUGENE, OR Contact: Ben Smith, benjsmith[at]gmail[dot]com Time: Wednesday, August 31, 7:00 PM Location: The Barn Light, 924 Willamette St, Eugene 97401 Coordinates: 84PR2WX4+VV Event link(s): LessWrong Notes: Please RSVP on LessWrong so I know how much pizza to get, but if you forget, don't worry about it, we want you to come along anyway PORTLAND, OR Contact: Sam F Celarek, support[at]pearcommunity[dot]com, 513-432-3310, Discord: Sam Celarek#2845 Time: Friday, September 9, 5:00 PM Location: 205 NW 4th Ave Coordinates: 84QVG8FG+V4 Event link(s): LessWrong, Meetup.com Group info: Portland Effective Altruism and Rationality is very active. We have book clubs, bi-weekly AI safety meet-ups, bi-weekly topical meet-ups, bi-weekly socials, and have an active Discord. Notes: We would prefer you RSVP on Meetup.com a week beforehand so that we can get the right amount of food! HARRISBURG, PA Contact: Phil, acxharrisburg[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: Ever Grain Brewing Co, 4444 Carlisle Pike, Camp Hill, PA 17011 - We will be sitting at one of the picnic tables outside with an ACX MEETUP sign Coordinates: 87G562QQ+8P Event link(s): LessWrong Group info: Small monthly meetup group based out of Harrisburg - celebrating 1 year of actuality! You can see more of our events on LessWrong. INDIANA, PA Contact: Eric, ericindianapa[at]gmail[dot]com, 717-256-2717 Time: Saturday, September 24, 11:00 AM Location: Caffè Amadeus in downtown Indiana, PA. I will have a sign with 'ACX Meetup' on one of the tables. Coordinates: 87G2JRFX+48 Event link(s): LessWrong Notes: Please RSVP via email or text message so I know how many to expect. PHILADELPHIA, PA Contact: Wes and Diana, rationalphilly[at]gmail[dot]com Time: Thursday, September 22, 6:30 PM Location: The Philadelphia Ethical Society, 1906 Rittenhouse Square. The meeting room is in the basement, look for the signs. Coordinates: 87F6WRXG+FQ Event link(s): LessWrong Group info: We tend to meet in downtown Philly on the last Thursday of the month. We're aiming to make the Ethical Society our new steady location. We have many links: Discord, Google Calendar, Facebook, Meetup, Google Group Notes: We'll be ordering food from a local restaurant, so no need to eat first. BYOB PITTSBURGH, PA Contact: Justin, pghacx[at]gmail[dot]com Time: Saturday, September 24, 2:00 PM Location: Westinghouse Shelter @ Schenley Park (W Circuit Rd near Schenley Dr). We have the outdoor shelter reserved, so light rain shouldn't be a problem, but in the event of extreme weather, we may relocate indoors (our default 'contingency indoor location' is Crazy Mocha Coffee on 2100 Murray Ave in Squirrel Hill). Coordinates: 87G2C3Q4+773 Event link(s): LessWrong Group info: We meet monthly-ish for general discussion and chit-chat, email me if you'd like to be notified of future meetups. STATE COLLEGE, PA Contact: John Slow, auk480[at]psu[dot]edu Time: Thursday, September 8, 5:00 PM Location: Old Main. I will be carrying an ACX meetup sign. Coordinates: 87G4Q4WP+HV Event link(s): LessWrong SAN JUAN, PUERTO RICO Contact: Dan Gelfarb, danielgelfarb[at]gmail[dot]com Time: Saturday, September 10, 1:00 PM Location: Lote 23, back corner under the tents. I will be wearing a blue shirt with a sign that says ACX meetup on it. Coordinates: 77CMCWVM+W32 Event link(s): LessWrong PROVIDENCE, RI Contact: James Bailey, feanor1600[at]gmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Prospect Terrace park, to the right of the Roger Williams statue Coordinates: 87HCRHJV+24 Event link(s): LessWrong SIOUX FALLS, SD Contact: S. C., villainsplus[at]protonmail[dot]com Time: Sunday, October 2, 5:00 PM Location: 410 E 26th St, Sioux Falls, SD 57105 - the pavillion on the west side of McKennan Park, or the tables just south of it if I can't book it. I'll be the guy with the grill. Coordinates: 86M5G7JH+W57 Event link(s): LessWrong MEMPHIS, TN Contact: Michael, michael[at]postlibertarian[dot]com Time: Monday, September 5, 1:00 PM Location: French Truck Coffee at Crosstown Concourse, Central Atrium 1350 Concourse Ave, Memphis, TN 38104. We will be at one of the many tables near French Truck Coffee and I will have a sign that says ACX MEETUP. Coordinates: 867F5X2P+QHC Event link(s): LessWrong Group info: We meet about every month or so. We've been around since 2019 but only regularly since mid 2021 due to the pandemic. We have a Discord server. NASHVILLE, TN Contact: Ellen, enwiegand[at]gmail[dot]com Time: Saturday, October 1, 11:00 AM Location: OneCity Nashville (8 City Blvd, Nashville, TN 37209), next to the volleyball courts. I'll have a pink ballcap that says SPINSTER on it. Coordinates: 868M552H+XW Event link(s): LessWrong AUSTIN, TX Contact: Silas Barta, sbarta[at]gmail[dot]com Time: Saturday, October 8, 12:00 PM Location: 4001 N Lamar, Austin Texas, park by Central Market near stone tables and tents Coordinates: 86248746+8C Event link(s): LessWrong Group info: Austin LessWrong has a weekly focused discussion, a weekly social mixer, a weekly online book club, and a monthly movie night. Been around since 2011. Notes: Location may change as we are talking to other venues BRYAN/COLLEGE STATION, TX Contact: Kenny, easwaran[at]gmail[dot]com Time: Friday, September 9, 5:00 PM Location: Back patio of Torchy's Tacos at Texas and New Main. I'll have a yellow umbrella and pinkish/purple hair Coordinates: JMFC+4J Event link(s): LessWrong DALLAS, TX Contact: Ethan Morse, ethan[dot]morse97[at]gmail[dot]com, Discord: ethanmorse#5255 Time: Sunday, September 11, 12:00 PM Location: Union, 3705 Cedar Springs Rd, Dallas, TX 75219. We'll be in the upstairs conference room. Coordinates: 8645R55R+9M9 Event link(s): LessWrong Notes: Please RSVP on LessWrong so I know how much food to get HOUSTON, TX Contact: Eric Magro, eric135033[at]gmail[dot]com Time: Sunday, September 18, 4:00 PM Location: Empire Cafe, 1732 Westheimer Rd, Houston, TX 77098 ---- Look for a table with an ACX MEETUP sign. Coordinates: 76X6PHVW+5H Event link(s): LessWrong Group info: There are meetups every week. We have a Discord and a Facebook group. WACO, TX Contact: Mike, BaylorACX[at]gmail[dot]com Time: Saturday, October 1, 1:00 PM Location: Cameron Park, picnic tables next to Jacob's Ladder Coordinates: 8634HVG2+V9 Event link(s): LessWrong Notes: Please email me if you're thinking about attending! Would love to start an ACX community here :) SALT LAKE CITY, UT Contact: Ross Richey (aka Jeremiah), wearenotsaved[at]gmail[dot]com Time: Saturday, October 8, 3:00 PM Location: Liberty Park near the ChargePoint stations Coordinates: 85GCP4WF+VJ Event link(s): LessWrong Group info: We meet every other month, we do book clubs and movie nights as well. Notes: Will be outdoors. If the weather looks bad, email event organizer to check on location. CHARLOTTESVILLE, VA Contact: RL, effectivealtruismatuva[at]gmail[dot]com Time: Sunday, September 4, 5:00 PM Location: 12 Rotunda Drive Charlottesville, VA 22903 - We’ll meet at the picnic tables across the street from The Virginian. There will be an ACX sign. Coordinates: 87C32FPX+3H4 Event link(s): LessWrong LYNCHBURG, VA Contact: Craig, craigbdaniel[at]gmail[dot]com Time: Saturday, September 17, 4:00 PM Location: Three Roads Brewing - I will be wearing a purple t-shirt and will place an ""ACX"" card on the table Coordinates: 8792CV65+5G NORFOLK, VA Contact: Willa, walambert[at]pm[dot]me Time: Sunday, September 18, 4:00 PM Location: Pagoda & Oriental Garden, 265 W Tazewell St, Norfolk, VA 23510. I will be wearing a bright green shirt, will have a large green & yellow hat on, and will have a sign with ACX Meetup on it. Coordinates: 8785RPX4+W3 Event link(s): LessWrong, Facebook event Group info: Hi! Virginia Rationalists was co-founded in Norfolk VA earlier this year by Willa & Yitzi with the goal of growing a thriving ACX / LW / EA community in our city & the state of Virginia. We meet every week at Fair Grounds cafe on Wednesday evenings from 5-7:30pm Eastern Time. We have a Discord server and a Twitter. RESTON, VA Contact: James, jrbalch333[at]gmail[dot]com Time: Saturday, September 24, 1:30 PM Location: The matchbox at 1900 Reston Station Blvd, Reston, VA 20190 on the 1st floor of the giant Google building. I'll be holding a copy of Sapiens. Coordinates: 87C4WMX6+9X Event link(s): LessWrong Notes: Email me to be added to the WhatsApp group RICHMOND, VA Contact: Cedar, cedar[dot]ren+acxmeetup[at]gmail[dot]com, @Cedar at this Discord server Time: Saturday, October 1, 2:30 PM Location: Richmond Public Libraries, West End Branch 5420 Patterson Ave, Richmond, VA 23226 Coordinates: 8794HFHQ+3G Event link(s): LessWrong Notes: Please RSVP on LessWrong & optionally reach out to me on Discord to introduce yourself! BURLINGTON, VT Contact: Forrest, lucidobservor[at]gmail[dot]com Time: Saturday, September 10, 2:00 PM Location: Battery Park, at the benches in the south-western corner of the park, near the cannons facing the lake. I will have an 'ACX Meetup' sign. Coordinates: 87P8FQJH+8P Event link(s): LessWrong BELLINGHAM, WA Contact: Alex, bellinghamrationalish[at]gmail[dot]com Time: Thursday, September 29, 5:30 PM Location: Lake Padden Park, at one of the tables near the lake by the dog park. If it's rainy, we'll meet in one of the two covered gazebo areas just north (right, if you're facing the lake) of the planned spot. If the forecast looks really bad (e.g. very cold), I'll post an indoor location to the Meetup.com page at least three days in advance. Coordinates: 84WVMHX3+GM Event link(s): LessWrong, Meetup.com Group info: Bellingham Rationalish discusses (in good faith!) topics in and around rationality. We usually meet the evening of the last Wednesday of each month. Our first meeting was a 2021 ACX Everywhere meetup. Notes: Please RSVP on Meetup so I have an idea how many people to expect. Kids, animals, food, beverages, etc. are all welcome. SEATTLE, WA Contact: Nikita Sokolsky, sokolx[at]gmail[dot]com Time: Sunday, October 9, 5:00 PM Location: Optimism Brewing (1158 Broadway, Seattle) Coordinates: 84VVJM7H+4Q Event link(s): LessWrong, Facebook event, Meetup.com Notes: Please RSVP on LessWrong (or FB/Meetup) for planning purposes MADISON, WI Contact: Mary Wang, mmwang[at]wisc[dot]edu Time: Saturday, September 10, 1:00 PM Location: 1022 High St. Blue house with red porches. If weather permits, we'll be in my large backyard, which has more seating now than last year. If rain, come in the side door. There will be air purifiers and open windows. Masks optional. Look for a sign at the end of the driveway that says ACX/SSC Meetup. Coordinates: 86MG3H3X+XW Event link(s): LessWrong, Facebook event Group info: We have met fortnightly in the past, but quit last year when it got too cold to meet outside. We typically have shared a meal, sat around my kitchen table and talked. Have held a Solstice celebration.
ritonavir

PF-07321332/ritonavir is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 23, 2021 and November 23, 2021. The archive places it in contexts such as "clinicaltrials.gov shows 11 studies, 7 still in progress, concerning PF-07321332/ritonavir [ie Paxlovid]"; "concerning PF-07321332/ritonavir [ie Paxlovid]". It most often appears alongside Andrew, clinicaltrials.gov, Dan Elton.

Reference entry
ritonavir
Mention count
1
Issue count
1
First seen
November 23, 2021
Last seen
November 23, 2021
November 23, 2021 · Original source
A quick look at clinicaltrials.gov shows 11 studies, 7 still in progress, concerning PF-07321332/ritonavir [ie Paxlovid]. Some are designed to look specifically at plausible bad interactions with common drugs. It's nice if the efficacy trial with ~1000 patients doesn't show any random safety problems, but it would be malpractice to not complete the safety tests on plausible bad drug interactions before unleashing it into a population that's going to be using it together with 100's of other drugs. Would you approve a drug without even a small test on people with hepatic impairment?
Andrew writes:
Zutano adds:
phenibut

phenibut is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 28, 2021 and April 28, 2021. The archive places it in contexts such as "Zembrin outperformed modafinil and phenibut on the survey". It most often appears alongside 2020 SSC nootropics survey, 852, BuyModa.

Reference entry
phenibut
Mention count
1
Issue count
1
First seen
April 28, 2021
Last seen
April 28, 2021
April 28, 2021 · Original source
I'm not sure. SSRIs are very effective for a lot of people. But Zembrin outperformed modafinil and phenibut on the survey. I have never heard even the most extreme fan of SSRIs (possibly me, honestly) claim people like them more than modafinil or phenibut. So this is either a bias (people think it's cool to be taking a new experimental plant, but don't like taking prescription medications with a bad reputation), or else Zembrin is either not an SSRI, or not just an SSRI. Of note, there are ways to prepare kanna (the plant Zembrin comes from) that make it kind of a recreational drug of abuse, though not a very addictive one. This suggests it has something more than just SSRI activity.
phentarmine

phentarmine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "I was on phentarmine back in the day and liked it fine". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
phentarmine
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Philip Morris

Philip Morris is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 20, 2021 and May 20, 2021. The archive places it in contexts such as "Tobacco giant Philip Morris…spent $ 75 million on its charitable contributions". It most often appears alongside 5D Chess With Multiverse Time Travel, AI X-Risk Research Podcast, Alignment Research Center.

Reference entry
Philip Morris
Mention count
1
Issue count
1
First seen
May 20, 2021
Last seen
May 20, 2021
May 20, 2021 · Original source
27: Harvard Business Review on when corporate philanthropy is good vs. cringe. My favorite sentence: "Tobacco giant Philip Morris…spent $ 75 million on its charitable contributions in 1999 and then launched a $ 100 million advertising campaign to publicize them."
Photofeeler

Photofeeler is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "to use the photo rating service Photofeeler to quantify the performance". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Photofeeler
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#27: Reverse-Engineer Dating Photo Quality I'm Loweren, a biology PhD doing photography and dating advice on the side. Some of you might know me from the Optimized Dating Discord server or the corresponding blog: https://optimizeddating.substack.com A keystone piece of advice in our community is to put more effort into making better dating photos, and to use the photo rating service Photofeeler to quantify the performance of each photo. This advice was helpful for many people, however there's one problem: it's not clear which factors make the photo perform better or worse on Photofeeler, as the developers are not keen on sharing the analytics. I will attempt to reverse-engineer the most important factors that make the dating photo look better by testing various factors (camera distance, focal length, aperture size, smile etc.) against the control photos using multiple subjects. I estimate that for each $80 in donations I can test 2 factors using 3 test subjects. I already have the first batch of photos ready to be tested. Results will be published on the blog as they come, which will hopefully help more people take better dating photos. My PayPal: https://paypal.me/seeelegance
Pierre Fabre

Pierre Fabre is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "gotten money from Pierre Fabre". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
Pierre Fabre
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Piggly Wiggly

Piggly Wiggly is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 26, 2023 and May 26, 2023. The archive places it in contexts such as "Clarence Saunders, 'the inventor of the modern self-service supermarket with his Piggly Wiggly chain'". It most often appears alongside /r/wallstreetbets, 2013 Financial Services (Banking Reform) Act, 80,000 Hours.

Reference entry
Piggly Wiggly
Mention count
1
Issue count
1
First seen
May 26, 2023
Last seen
May 26, 2023
May 26, 2023 · Original source
Piggly Wiggly Stores Inc. was a publicly-traded company with sound financials. However, there was a bit of confusion by investors over the difference between "Piggly Wiggly Stores Inc.", "Piggly Wiggly Corporation," and a third different company which went bankrupt at a time when it had run a number of locations franchised by Piggly Wiggly Corporation. (Many saw the words "Piggly Wiggly" and "bankrupt" in the same headlines and assumed that the story had something to do with the publicly traded company "Piggly Wiggly Stores Inc.")
For one thing (unlike Gamestop), Piggly Wiggly Stores Inc. was a firm that actually seemed to have sound financials. For another, Clarence Saunders was attempting to execute this short squeeze in 1922, when stocks were traded as physical pieces of paper, making the system of "IOUs" that enable short-selling much more tangible, and the market far less liquid (and thus easier to corner or manipulate). And perhaps most significantly, Clarence Saunders was not a third-party rallying people on an internet forum; he was buying his company's shares using shares from his own personal funds, money he had borrowed (which ended up millions of dollars, a huge amount in 1922), and the company's funds.
The act of using funds from the Piggly Wiggly Stores Inc bank account to buy shares in Piggly Wiggly Stores Inc. sounds a lot like a "buyback" (something which companies do from time to time; Apple seems to be a particular fan of the practice having done it most recently in 2022), but nowadays the SEC has strict rules about when and how buybacks can be executed, and many aspects of buybacks as we understand them today weren't formalized until the 1980's.
Pinterest

Pinterest is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "change all the computers to say Pinterest". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Pinterest
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
We did all kinds of pretty desperate things, honestly. I used to walk by the Apple store on the way home. I’d go in and change all the computers to say Pinterest. Then just kind of stand in the back and be like, “Wow, this Pinterest thing, it’s really blowing up.”
Pixar

Pixar is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 14, 2023 and July 14, 2023. The archive places it in contexts such as "Now, all lessons can’t be Pixar movies". It most often appears alongside !Kung San, aboriginal people on the west coast of Canada, Adam Smith.

Reference entry
Pixar
Mention count
1
Issue count
1
First seen
July 14, 2023
Last seen
July 14, 2023
July 14, 2023 · Original source
From trivial to rich: the trick What could an intellectually rich elementary school curriculum look like, if we built it on kids’ cognitive strengths? He gives us one suggestion to help us do this: ask where each discipline came from in the first place. What was math before it was math, for example — or science before it was science? Q: How on Earth could that help? That’ll become clear later, when we finally uncover what Egan thinks “education” actually is, and see what job he wants us to give schools. For now, take it as a tantalizing hint… or, y’know, just ignore it. Elementary literature & language What was literature before it was literature? Before people invented writing, they had rich oral traditions: they told simple stories, recited poems, and shared proverbs. Egan suggests that these bits of oral tradition should form the backbone of the elementary literature curriculum. Q: What sorts of stories? As many as we can, and from as many diverse cultures as possible! Folktales are wonderful, as are myths. Think the Aboriginal story of “The Rainbow Serpent”, episodes from the Sumerian “Epic of Gilgamesh”, the Egyptian story of Osiris & Isis, the Greek story of Orpheus & Eurydice, the Chinese Legend of the White Snake, the Japanese Tale of Amaterasu and Susanoo, the Ashanti tales of Anansi, the Aztec myth of Quetzalcoatl, the English legend of King Arthur, the Maori myth of Maui and the Sun, the Roman story of Romulus and Remus, selections from the Indian Mahabharata, the Anglo-Saxon epic of Beowulf, the Inca legend of the Sun and Moon, the Iroquois Myth of the Flying Head (a real thing! look it up!), and the Ojibwe story of Turtle Island. Q: That was a lot of examples. Are you going to keep giving so many? I’ve got a [mumble mumble mumble] to get to. Sorry about that. Sometimes, though, I feel that a limitation of reading Educated Mind is that, in trying to keep his book to a manageable size, Egan skimped on examples in some places that it matters. It’s easy to read his occasional example and assume he intends that it hold some central place in the curriculum — when all he wants to do is display how rich and diverse the curriculum could be. (Also: good God, I didn’t even include an example from Norse mythology!) So from now on, just assume that every category could be filled with oodles of examples. Q: What sorts of poems? Lots of poems, first of all. We shouldn’t steer toward “fancy” poems — rather, we should find poems that appeal to kids immediately — think Shel Silverstein, Mother Goose, Dr. Seuss, Jack Prelutsky, Edward Lear, or Ogden Nash… that sort of thing. In a biting essay, Egan suggests these poets like these appeal to kids precisely because they leverage kids’ cognitive strengths: “we should find, and encourage saying and singing and shouting aloud verse with strong narrative forms, thumping rhymes and rhythms, the most vivid images, fun with metaphors, and a rollicking story.” Q: Why proverbs? Proverbs stick in your mind almost effortlessly. (“All’s fair in love and war!” “When in Rome, do as the Romans do!” “You can’t judge a book by its cover!”) They’re also useful; they capture general truths. Kids can apply them to all sorts of situations, but also discuss them — to what extent are they wise or foolish? (I remember my surprise when I realized that they couldn’t all be true — because you can’t follow “look before you leap” and “he who hesitates is lost” at the same time! I’m embarrassed to say that I think I only realized this when I was in college.) Elementary science What was science before it was science? Egan suggests: being immersed in the natural world. We might, he writes, encourage elementary students to “adopt” some feature of the natural world — a patch of grass, a cat, a branch, a stream — and simply observe it at length. To do this, we can use the cognitive strength of reverie. Q: Oh, do you mean like kids sometimes do in science class nowadays — describe a thing to a partner, make notes, draw it, and label its parts? No, the exact opposite! That’s all about squeezing the experience into words and forms that we understand. What we want “is less an attempt to know about nature as to know it in some participatory way, to know it as something we are an intimate part of, not set off from”. Q: That sounds a little… “woo” to me. It did to me, too… until I remembered my childhood climbing tree. I didn’t much like to go outside as a child, but I had this one tree that I’d climb up and read for hours and hours. If I close my eyes I can bring to mind the precise texture of its bark, the roughness of its broken-off branches, the coolness of its leaves, the always-surprising solidness of its trunk… I’m bigger now, but I think if I were back in my parent’s yard, I could still navigate its limbs with my eyes closed. I have, at this point in my life, read a fair number of books about trees, but I’d be surprised if all of them together more than equaled the amount I learned from that tree — my tree. Elementary math What was math before it was math? Egan suggests: counting and logic. We might, then, use rhythms, metaphors, stories, and jokes to help kids become fond of these. Q: Counting is pretty… basic. Could it really be improved? Beware of “the curse of knowledge”: Steven Pinker’s phrase for forgetting that something was once difficult! Egan suggests we should spend time helping kids count wonderfully. We can start early with counting rhymes. (“One, two, buckle my shoe! Three, four, out the door! Five, six…”) But we can also help kids use their fingers as metaphors. There are some pretty cool ways of using your hands as an abacus — and did you know that you can count up to 1,023 using just your fingers on both hands, and a knowledge of binary? Q: Logic — I’m intrigued! Aristotelian, or Boolean? Neither, for the time being — Piaget was presumably onto something when he found that young children couldn’t reason abstractly, but he was looking at logic in a vacuum. When we put logic into the context of stories, we find that kids can deal with logic just fine. There’s an entire worldwide network of educators, in fact, called Philosophy for Children, who have written whole books about how to do this, and Egan loves it all. Sometimes they read stories and ask simple questions: “What is friendship?” or “What does it mean to be brave?” They also pose ethical questions: “Is it ever right to spill a secret?” And they pose paradoxes: “Can you step in the same river twice?” Q: You mentioned “jokes” a moment ago. Care to elaborate? Egan thinks that, to help kids get good at math, you should tell kids jokes. Q: That’s… new. I think so, too — but he backs it up pretty well. To be funny, jokes (or at least most kid jokes) rely on a leap in logic: Why can’t you trust an atom? They make up everything. Knock-knock. Who’s there? Boo. Boo-hoo? Don’t cry, it’s just a joke! To understand the joke, kids have to follow the logic — spotting patterns, making connections, and tracking what their audience expects a word to mean. That’s a lot of cognitive lifting. And Egan goes further, suggesting that we grit our teeth and create methods to help kids invent their own jokes, no matter how horrible they’ll be at first. (The things we do for learning…) Q: Wait wait wait! What about addition facts, and multiplication tables, and fractions? Egan emphasizes that his methods are designed to be add-ons to the standard math curriculum. In general, he’s a don’t-blow-up-the-system sort of guy, and if something seems especially weird, you should probably assume it’s an add-on to the regular curriculum rather than a replacement, even if I forget to say so. Elementary arts What was art before it was art? Egan suggests we pop our heads into Paleolithic caves for our inspiration. Whatever the specific meaning of all those charcoal elk and aurochs and mammoths (communication with the spirit world? art for art’s sake? a way to impress babes?), Egan thinks it obvious that they were also an attempt to capture an intense experience that would be difficult to express in words alone. What did it feel like to be near an aurochs, or a saber-toothed tiger? “The arts help us,” Egan writes, “to hear and see afresh, to force our perceptions and sensations to experience again the immediacy and vividness of the world”. If we follow this, then, we don’t want to help kids build “art skills” so they can draw like an adult — rather, we want to help them amass a repository of diverse aesthetic feelings that they’ll want to express. We should provide them with a riot of experiences. Q: That couldn’t be more opaque. Examples, please! Egan writes that we should have children learn to whistle, sing, and click their tongue; we should help them emulate the ways a skunk or a hawk or a stick bug might move through a space. We should expose them to scores of different temperatures and materials. In music, we should help them love Beethoven, yes, but also the Beatles; Tchaikovsky, yes, but also Tuvan throat singers, and also John Cage, whale song, and bird song. Q: That’s a lot of experiences, but what would they be doing? An interesting aspect of Egan’s view of education is that he doesn’t seem to think we should push kids right to the “doing” phase. He wants to help kids cultivate an affective relationship with the world. In any case, he writes that as students get more experienced, we should prompt them to move from merely enjoying these experiences to trying to systematically shape similar experiences. And drawing, painting, and playing music could easily be folded into other parts of the curriculum. Elementary social studies What was social studies before it was social studies? Well. Remember how, just a moment ago, I wrote that you could assume that you should probably assume that Kieran isn’t in favor of junking the curriculum as it currently stands? He suggests we very carefully pick up the elementary social studies curriculum, place it into a trash can, and set the whole mess on fire. He isn’t worried about much of importance being lost. (Remember that the “expanding horizons” model is, to him, the original sin of 20th century educational reform, and he repeatedly quotes student surveys showing that “social studies” regularly wins the title of “most boring subject”.) In its place, he suggests we put history — which, he hints, we should think of as the centerpiece of the elementary curriculum. So the real question is what was history before it was history? His answer, surprisingly, is myth. Q: Egan wants us to teach myths as if they were history? Not at all. What he suggests, though, is that we look at how myths operate as narratives — so we can design an intellectually vivid history curriculum. And myths really are special: each is built on at least one binary (like weak vs. strong, or lies vs. truth, or so on), and uses that to tell the story of the big picture of the world. They’re so powerful that people can understand it, remember it, and love it — even if that thing never happened. We should take that power, Egan says, and apply it to things that really did happen. Q: So what history does he think kids should learn in elementary school? The great struggles of humanity from across the whole. Flippin’. World. We’re still talking about young children, so these should be done as simple stories. The goal isn’t to make them history PhD’s, so we needn’t even try to put them in any sort of order. Egan suggests that, in first grade, we pick a single binary like “freedom against oppression” and tell kids a welter of stories, again from as many cultures as possible, and as many times in history as possible. Q: Can you give examples? Oh, all right — in first grade we can tell kids the stories of the war of the Greek city-states against the Persian empire, and the slave uprising of Spartacus against the Romans. We can tell them about the plight of Jews in medieval Europe, and of the unsuccessful Sepoy Rebellion in India against the British. We can tell the stories of the American, French, and Haitian Revolutions, and about the Chinese Taiping Rebellion against the Qing Dynasty. We can tell them the story of the escaped slave Harriet Tubman returning to the South to rescue her kinsmen, the story of six-year-old Ruby Bridges facing threats to integrate her elementary school, and the story of how the Mau-Mau uprising led to modern-day Kenya. We can tell the stories of Mexican-American union organizer Cesar Chavez and of Malala Yousafzai surviving an assassination attempt to advocate for female literacy. The world does not lack for stories of oppression and liberation that can capture the attention of a six-year-old. Q: That’s… huh. What stories might they hear in second and third grade? Egan gives examples, but I won’t list them here. He suggests we use a similar approach for each, except that we swap out the binary each year. He thinks “the struggle for security against danger” would work well for year two, and “the struggle for knowledge against ignorance” would work well for year three. (That year could have a lot of overlap with the science curriculum.) Q: Anything else, for history? Yes — they should get a sense of Big History. They should get some simple stories about the ice age, the Cenozoic, the age of dinosaurs, the Paleozoic, the origins of our solar system, and the Big Bang. (Because if the ancient Norse can tell their story of the beginning of the universe, by gum, we can tell ours, too.) To sum up Egan argues that the problem of early schooling is that it’s trivial — and it’s trivial because the dominant theories of educational psychology see children as lesser versions of adults. What else would we teach them, except dumbed-down versions of what adults learn? But children have certain cognitive strengths that schools aren’t making systematic use of. If we rebuild elementary schools on those strengths, we could turn schooling upside down. We could stop seeing the curriculum as a bag of information to impart, and start seeing it as a set of great stories to tell — and invite kids into. Kids could experience (both intellectually and emotionally) the great struggles of humanity and see that they can join in them. Students could experience the story of education as the beginning of a very real adventure. Egan’s elementary school: some skeptical questions Q: I’m not sure I’m understanding what you mean by “mental images”. Care to explain? It’s an interesting fact of human cognition that just a few words can whip up a complex mental experience. Egan doesn’t just mean what we might call “visual imagery” — the ability to hold, say, the image of a bespectacled, spat-wearing duck in your mind without seeing a photograph. He’s also including what psychologists call auditory imagery, olfactory imagery, gustatory imagery, and tactile imagery. Q: How could all of that be helpful in schools? Humanity has a built-in VR system, and we’re not using it! Egan invites us to pretend we’re teaching a class about the humble earthworm. We might list off facts — “earthworms are so many centimeters long, move through soil by means of their something-or-other muscles…” but he suggests we can evoke images, say, “of what it would be like to slither and push through the soil, hesitantly exploring in one direction then another, looking for easier passages, contracting and expanding our sequence of muscles segment by segment, and sensing moisture, scents, grubs, or whatever”. Those facts are now felt by the student; the knowledge has become part of them. And just a few words can spark a complex mental experience, one going beyond literal images to include imagined sounds, smells, tastes, and more. These experiences can feel real and stick with us. (That these mental images are so easy to evoke, and so meaningfully felt, feels something like the proverbial hundred dollar bill on the ground.) Q: How could metaphors be helpful? It really is interesting that so much of the “constructivist” turn in psychology — that is, the notion that children don’t absorb knowledge, but construct it — has continued to focus on logics-mathematical reasoning, when there’s been mounting evidence for decades that metaphors are more central. It’s not just that we use metaphors to better understand things we already know, we also use them to grasp new knowledge. What’s more, psychologists have devised tests to measure the skill at metaphor-making, and have given them to people of different ages. What they found was that eleven-year-olds make more metaphors (and higher quality metaphors) than do undergraduates — and that four-year-olds have both groups beat. Again, hundred dollar bills on the sidewalk. Q: Your talk of “binaries” has me worried — binaries like good/evil and male/female are the source of so many of our most pernicious stereotypes! Isn’t the purpose of education to get us beyond stuff like this? Yes, it is! Education is supposed to complicate our understanding — but that means we’ve gotta start somewhere, and binaries provide us a natural starting place. As an uncontroversial example, think about temperature. We all begin as babies by perceiving two temperatures — hot and cold. Later, we add on intermediate categories — warm and cool. (Note that the human body is the assumed mid-point to temperature. Binaries often work like this; “big” and “small” mean “bigger or smaller than me”, “nasty” and “kind” mean “nastier or kinder than I am, except when my brother is really asking for it”, and so on.) A good story (and an Egan-inspired elementary curriculum is, in a sense, nothing but good stories) will go further, and transform the binary. Toy Story is grounded in the binary of abandonment/belonging: at the beginning, the toy cowboy Woody belongs to his owner, and has his affection. Then a rival comes who threatens his belonging. In trying to get back to belonging, Woody is entirely lost — and to save the day, he has to come to a deeper understanding of what belonging means. Now, all lessons can’t be Pixar movies. But the good stories (especially in literature and history) will challenge and subvert the binaries they begin with. Q: I see the pattern of Egan drawing from “as many cultures as possible”. Why so many? Is this a political correctness thing? If it helps to think of it as such, then, sure! I don’t think Egan would have had a problem with that. But his ultimate reason for including so much diversity goes deeper. For Egan, including such world-wide diversity isn’t optional, and the answer to why is bound up in his definition of education. (Keep reading.) His answer also insists that we, whenever possible, also include stories from the Bible and Homeric epics (the Iliad and Odyssey). Q: Mmm, stories from the Bible aren’t going to fly in my local school! So be it! Egan doesn’t spend much time obsessing over the practicalities of… His interest is in describing what an ideal education might look like, if it were possible. Every lesson, every classroom, and every school is necessarily a compromise. Q: You make a big deal of poems. But isn’t poetry dead? An interesting contrast can be made to classical education, which also has kids read a lot of poems — they see knowing great poems as one of the marks of an educated person; again, for an academicist, it’s the information that transforms. Egan begs to disagree. Poems are important because they’re a wonderful way to train their cognitive strengths, like rhythm (poems are language fueling by thumping). We want to help kids learn to use this tool better, and a great way to do that is to help them recite poems that they’ve learned by heart. Q: “Learn by heart” — is that code for “memorize”?! It is! Egan is actually quite big on memorization — he points out that all the knowledge in the world can do nothing for a person once they’ve forgotten it. He didn’t, however, appreciate the academicist focus on memorizing without understanding (or at least enjoyment). Q: I’m still worried about the science curriculum, as you’re describing it. Can you allay my fears? Honestly, while I feel there’s something profoundly right to how Egan is describing early experiences of nature, I feel the same way. Note that there’s more science coming in the social studies curriculum. But if that’s still not enough, one could bring down aspects of the middle school science stage. Q: Anything else that Egan suggests we do in elementary school literature and language? He suggests that we help kids learn a second language! This is so obviously true (why do American schools typically wait until kids lose the ability to naturally absorb languages to start teaching languages?) he doesn’t belabor it, though. Q: You had mentioned that Egan’s vision seems more internal-focused. Should we be worried about that? While I strongly suspect that his curriculum would make kids more creative in any way you’d like to measure it, Egan wasn’t particularly interested in “creativity” — he was more about helping kids find the world interesting. I get the sense that he thinks kids will do things with minimal prompting once they’re loaded up with complex internal experiences. Q: I think I’m beginning to understand Egan — is he basically saying “make learning fun”? “Fun”, applied to education, is a dangerous word. Egan worries about the dangers of an emotionally unserious curriculum producing emotionally stunted adults. That doesn’t mean we need to tell students only “serious” stories — only that we treat the world honestly. “Disney-esque sentimentality is the exact emotional equivalent to intellectual contempt”. Q: But aren't some of these stories too dark for children who have themselves experienced oppression and disaster? Egan argues that these stories may be especially helpful to them — they can help them understand their struggles better, and give voice to them. Q: At the very start of this, you promised us “rationality”… but I’m not seeing rationality here! All this talk of “adventure” almost seems to go the opposite direction. What gives? Wait for it. But for a hint right now — Egan is fond of citing his fellow educational theorist Jerome Bruner, who claimed “any subject can be taught effectively in some intellectually honest form to any child at any stage of development”. Bruner was criticized for that; his critics charged that he was ignoring learning differences and socio-economic realities. Egan thinks he was profoundly right. Part 3: A new kind of middle school What’s the matter with middle school? What was middle school like for you? In math, I recall a jumble of barely-related topics. In literature, I remember reading great literature — Frankenstein, Romeo and Juliet — only in their dumbed-down summary formats. In social studies, I remember teachers proclaiming on the first day of class that unlike all of our previous history classes, this class wouldn’t be about names and dates… and then going on to memorize names and dates. And in science, I remember being forced to dissect a frog only to discover that frogs are — you guessed it — made of slimy frog parts. Your mileage may vary, but for a lot of us, middle school feels like getting booted out of the (in retrospect) Eden of elementary school, and like marking time before the serious studying of high school. It feels meaningless. In my favorite of his books, Egan calls so much middle school curricula “human deserts”, noting “we have created a system in which the importance of human emotions for meaning seems barely noticed”. Why so meaningless? If our dominant approaches to educational psychology fundamentally misinterpret younger children, Egan suggests, they basically throw up their hands when faced with pre-teens and teenagers. Mainstream schools begin to introduce vocational training to help lighten the load, and Maria Montessori famously suggests that adolescents should be sent to go run a farm. Egan is sympathetic to those responses, but points out that they don’t do much to lighten the load that the academic curriculum often becomes at this age. This feeling of meaninglessness, he argues, is utterly tragic — it comes just when a hunger for meaning blossoms in adolescents! We can see that hunger for meaning in their lives outside the classroom, where their interests ramp up into veritable obsessions. What are adolescents obsessed with? What might we see, if we become Jane Goodalls of early adolescence? First, teens are obsessed with gossip. The motivations of others — why did he do that? and what was he THINKING? — are hypothesized and talked to death. Second, that they’re pulled toward idealism. Many feel a dissatisfaction with the world as it is, and feel a romantic urge to make it a better place. They’re often lured into simplistic beliefs that promise to help them do that. Third, they love extremes: they want to find limits, and test them. Obviously, this can show up as risky behavior, but we can also see it in their love for the bizarre — note adolescents’ fascination in things like aliens, cryptids, and ghosts. (Egan loves pointing out that The Guinness Book of World Records is a perennial bestseller among kids at this age. How else would they find out who had the world’s longest fingernails?) Fourth, they gravitate toward heroes — people who push the edges of those limits. By celebrating heroes, they can vicariously share in their transcendence. Look for the posts hanging up in a teenager’s bedroom to guess what boundaries they feel most hemmed in by: athletes push against physical limits; a death metal guitarist might push against authority and conventional morality. An activist or entrepreneur might push against our dulled morality or our sense of what’s possible. Finally, we might spot teens taking up hobbies and making collections. Hobbies can be a way to identify yourself as part of a group against the rest of the world (“I’m the sort of person who goes bird-watching!”), and collections can be a way to climb the status ladder inside the community. Egan points out that a collection can also be a way to feel like you have control over what you’re discovering is a very big and complex world of detailed information (“I’ve spotted every one of the fifty most common birds of Texas — even the black-capped vireo!”) Egan’s insight is that these obsessions give teenagers a sense of meaning, and that we can use them as tools to make middle schools that overflow with meaning. From meaningless to meaning-soaked Again, Egan sketches out a new kind of curriculum subject-by-subject. Before, his trick was to ask where the subject first evolved out of; now, it’s to ask who first discovered or created the specific content we’re teaching. “All knowledge”, he writes, “is human knowledge. Everything we know is knowable through the lives of its inventors, discoverers, or users, and we can have access to that knowledge through the hopes, fears, or intentions that drove them”. Middle school math Who first discovered the concepts students learn in math? The answer, of course, is a wide diversity of curious men and women living across the world over the last few thousand years. Egan says: bring those people into how we teach math. If we used gossip and heroes to help students find it meaningful, what kind of math would result? When we teach the Pythagorean theorem, we should give a sense of who Pythagoras was — a cult-founder who worshiped numbers to find God, whose followers (according to a piece of ancient gossip) murdered one of their members who discovered irrational numbers! Q: Well, sure, that works for Pythagoras, but he’s a known nut job; surely most math doesn’t come from such interesting roots? When we teach the Cartesian coordinate system, students should meet Rene Descartes, the Calvinist French polymath who saw the possibility that math could decipher the world, if only we could unite algebra and geometry… and invented the xy-plane to do exactly that. When we teach scientific notation, we should call our students’ attention to the importance of the number zero, and tell them the story of the Pope who tried to introduce Arabic numerals to Christian Europe and may have been assassinated because of it. When we teach algebra, we should ask students why “algebra” is Arabic for “the fixing of bones”, and tell the story of what Muhammad ibn Musa al-Khwarizmi was up to. We could do this all day. Literally everything students learn in school was first invented or discovered by some interesting person who was struggling to accomplish something hard. To learn is to connect with those people, whether we know it or not. Egan says: help kids know it. Math has been dehumanized: re-humanize it. Q: So the math curriculum needs to become a history of math curriculum, and math teachers need to become history teachers? No, the content needn’t change. But with surprisingly little work, we can bring in the gossipy stories of heroes, and their obsessions can spread to students. Middle school science Who first discovered the things students learn about in science? If you’re thinking “scientists”, you’re only partially right. Most of the big-picture ideas that we now think of as “science” were discovered before the word “scientist” was invented, or the discipline was professionalized. Frequently, they were hatched by true amateurs, working in their free time, hungry to unlock the secrets of nature. We can use gossip and heroes to spread their obsessions to students just as we taught math, but Egan points out two twists. The first is that the content itself can take on heroic qualities: everything is impressive, when you look at it in a certain light. In an interview, Egan once said: “My book is an attempt to show that, indeed, everything in the world is wonderful, but that schools are designed almost to disguise this slightly shameful fact. We represent the world to children as mostly known and rather dull. The opposite is the case: we are surrounded by mystery, and what we know is fascinating”. What would even the most boring subjects look like, if we emphasized their heroic qualities? Well: What’s a tooth? Bone, wrapped in rock, surrounding tiny cells that your body feeds with blood. What’s a bar of chocolate? A crystal of jellyfish-shaped fat molecules stacked together; when you put it in your mouth you shake them apart into a writhing confusion. What’s the air around you? The bottom of a 10-mile-deep ocean; when you put your tongue over a soda straw and your Pepsi stops leaking out, it’s not because a “vacuum” is “sucking” it up, but because that ocean is squeezing it into your face. Again, we could do this all day! And in middle school science, we can. Everything in the world is wonderful; we can help students see this again and again. The second twist is that science is a subject rich in extremes. Here Egan introduces a concept that we’ll see crop up again: “15-minute segments”. To help us fit as much wonder as possible into a school day, he suggests we supplement the usual school subjects with a few quick lessons. To infuse science with extremes, he suggests we add on three: “human & natural records”, “extremes of animals & plants”, and “cosmology”. Middle school history Who first made the things students learn about in history? Why, the historical characters themselves! Since we’ve given kids a grounding in history in elementary school, now we can build on that, going through many of the same events as before, but in more depth, and more vividly. We’ll leverage the interest with other people’s inner lives to tell stories focusing on the perspectives of the people who made history — zooming in, when possible, on scandalous details. We’ll leverage the tool of idealism to choose historical characters who chafed against their surroundings, and understand what they were trying to accomplish. What was their vision of the world? What did they hope for, and what did they fear? Q: Isn’t the “great man” approach to history out of fashion? Egan’s approach doesn’t say that “great men” made history — it’s just leveraging gossip to help kids see history as something meaningful that can expand their own possibilities. “Early adolescence is commonly a time of intense and vivid emotional life, and also a time of deepest boredom and depression… [We] can give shape to the intermediate curriculum and offer the students a world that is rich, complex, varied, and as intense and vivid as their own emotional lives”. We also should add on another “15-minute segment” just to pump in as many biographies as possible, and from people who don’t always fit into the normal history curriculum. Call it “Brief Lives”, and throw in anyone who’s struggled to push some limit — Mary Wollstonecraft, Jesse Owen, Dietrich Bonhoeffer, one of the students’ great-aunts, whoever. As students get older, this can transition to “People and Their Ideas”. Here, we’d focus less on the details of the person’s life, and use it as a backdrop to showing how meaningful some of history’s most important ideas could be. Think Aristotle and syllogisms, Edward Said and orientalism, Confucius and propriety, Cornel West and race, Buddha on the four noble truths, Muhammad and the five pillars, Karl Marx and communism, Adam Smith and the invisible hand, Thomas Hobbes and the state of nature, John Locke and natural rights, Jeremy Bentham and utilitarianism, Thomas Aquinas on the sacraments, Martin Luther on faith, Voltaire on the freedom of speech… you get the idea. Q: Can you really get a profound understanding of utilitarianism in 15 minutes? Yes! The point of this segment isn’t to develop a systematic understanding of any one idea, it’s to introduce students to the exciting possibilities of human thought. (As a bonus, this might make them less likely to fall for the first ideology that they encounter later in life.) Diversity is important for this — as it is with culture. Throughout this, we should also be trying to expose students to as much cultural diversity as possible, because in high school, we’ll be trying to make sense of our society, and it’s impossible to do that unless we have something to compare it against. Middle school literature & language You might think that this subject would be easy — that middle school literature is already filled with “strong and clear narratives”, that it deals with “transcendent human qualities such as courage, love, and persistence”, that it focuses on “extremes of human experience”, that it examines “something strange and exotic”. You’d be right! Egan’s pretty happy with a bog-standard middle school literature curriculum, done well. In this part of the book, his spends most of his limited space suggesting three rather odd activities which could also be useful — especially for increasing students’ awareness of language, so they can use it better. The first is etymology — not, however, memorizing lists of roots, but in being told the entertaining backstories of specific words. Take the word “berserk”, for example — we now use it to mean something relatively mild (“if my mom catches me coming home late, she’ll go berserk”), but it comes from an old Norse word meaning “a raging warrior of superhuman strength”. And that’s because ber meant “bear” and serk meant “shirt”: soldiers of the bear cult would don the skin of a bear to, in their minds, transform into one — howling, foaming at the mouth, and gnawing the rims of their shields. (Most adults walk through life with little understanding that the words falling out of their mouths are entities, with their own back-stories. Communication is, at the very least, more interesting when we become aware of this.) The second is to add on another language to learn — not, this time, to become fluent in it, but just to become aware of how very different human languages can be. (For native English speakers, Sanskrit might work well, or Cantonese, or perhaps even ancient Egyptian. Again, the point isn’t for this language to be useful — it’s to explore diversity.) The final one is to study humor — not just jokes anymore, but comedy at its finest. Egan cites (at length!) Monty Python as a group of people who were particularly brilliant in their use of the English language. Examining their skits can lead us into not just an appreciation of semantics (the study of how meaning is made from smaller pieces, like etymology) but also pragmatics (the study of how meaning is made in social situations). Pretty heady stuff, for a conversation about a dead parrot. Part 4: A new kind of high school I’ll confess — I loved parts of high school… and among nerdy folks, I suspect I’m not alone. For some of us, this was a golden time. Even at my local public high school, I had access to academically thrilling classes — especially, in my last two years, advanced literature and history. I felt like I was finally understanding the ideas that mattered. In any case, Egan is quick to acknowledge that, at this level, the sort of education he advocates really is being practiced in some places. What he can add is an understanding of what makes it wonderful, how to make it even more wonderful, and how to make it wonderful for many, many more people. What’s the matter with high school? Far too often, even when high school classes are intellectual, they’re dry. For the majority of students, all this academic stuff is experienced as utterly lifeless, a mass of dead information to be squeezed inside one’s head for a test and then left to evaporate. Egan mocks the curriculum wars that seem to be a permanent feature of the teaching life; quoting the sociologist Pierre Bourdieu, he says “while the academic left and right bicker over whether the curriculum is too traditional or too radical, they fail to recognize that most students absorb so little of academic culture that the bickering is largely irrelevant”. Why so dry? Egan suggests three reasons to explain this. First, because high school academic classes are too often masses of small details with no sign of the big picture. Second, because they’re typically slavishly disciplinary, and aren’t able to address the questions that span the disciplines. Third, because they’re often designed to bring students through what everyone is sure of, and hide away any controversies. In all of these, Egan suggests that what’s called “academics” in high school is too often a dim imitation of what real academics are actually practicing. There’s a fourth reason, though, and it’s probably the biggest of all — by the time they get to high school, most students haven’t actually learned that much! An academic approach is designed to connect small details into the big picture; for people who arrive in high school (and college) classes without having already collected much in their heads, academics are going to taste dry. (An implication of this for anyone trying to improve schools is that we might not want to start with high schools. If your goal is to create a new kind of academic learning, first start at elementary school — or barring that, middle school.) What motivates mad scientists? When we wanted to re-conceive the elementary and middle school curriculums, we looked at what students were already good at — kids’ cognitive strengths and adolescents’ obsessions. For this level it might be easier to look — for reasons that will become clear when we finally unveil Egan’s crazy-sounding definition of education — at the sorts of things that bring intellectuals joy. Q: Which intellectuals? Take your pick. Galileo, Einstein, Smith, Marx, Goodall, Chomsky, Curie… all the people who took to the life of the mind like fish to water. But that’s a lot to hold in my mind at once, so I’m just going to think about Doc Brown from Back to the Future: He was high on intellectualism I’ve never been there, but the brochure looks nice Let’s call these people “mad scientists”. And let’s pretend we once again took up our job of being primatologists, and snooped on these folks “in the wild” (“in the lab”? this is beginning to get recursive…)… what would we find motivating them? Asking simple questions, for one. (What is space? What is society? What is a human? What is language?) Building general schemes (big theories) that hold lots of evidence together. Finding their place in the cosmos. And (perhaps above all) seeking certainty. Once again, Egan suggests we use these as tools to remake the curriculum. From dry to daring What could a high school curriculum look like, if it were rebuilt on these tools? Once again, Egan has a trick. This time, it’s to ask what fights have driven the development of each of these fields forward — and how we can help students enter them. First, a mini-segment! Intellectuals invented the academic disciplines to better pursue the life of the mind, but the disciplines can get in the way. Some of the most important intellectual discoveries that could help students are too big to fit into any of the disciplines. We need a place to introduce them plainly. Egan proposes another mini-segment — again, just 15 minutes a day, a few times a week — called “Metaknowledge”. Q: Isn’t that already in the International Baccalaureate program? Yes, he acknowledges that he’s borrowing from that! This segment would introduce ideas that would enrich student thinking across the disciplines: game theory, cognitive biases, systems thinking, Bayesian reasoning, epistemology, ethics, logic, cultural evolution, and so on. High school literature How can we help students enter the big fights of literature? Intellectuals of a literary bent — professors, critics, poets, novelists — delight in arguing over literature like rabbis arguing over the Talmud. Take, just for one example, the debates over Shakespeare’s character of Ophelia. Does she love Hamlet, or is she a victim of his emotional abuse? Is she truly insane, or is she acting? Is she passive, or is she pulling the strings? Oceans of ink have been spilled arguing over questions like these; our students can, perhaps, spill a few ounces more. The usefulness of arguing literature, for Egan, isn’t that it’s oh-so important for educated adults to know a lot about Ophelia. (This, again, was where the academicists went wrong — in thinking that being educated was about getting the best knowledge in your head.) Rather, arguing over literature is a training arena for the all-important intellectual move of this kind of understanding: building general schemes out of evidence, and struggling with anomalies. One person, for example, might hold that Ophelia is insane, and cite all sorts of obvious evidence — her father just was murdered by her lover, she rants nonsense while (bizarrely) handing out flowers to friends… But then he’s challenged when he reads a scholar pointing out that, to people in Elizabethan England, types of flowers have symbolic meanings. How does he deal with that? He could ignore it, claiming it an over-reading of Shakespeare. (Sometimes a flower is just a flower!) Or he could address it, complicating his own scheme. This intellectual work is best done with other people, who are incentivized to challenge your understanding of something, and go back and forth, building competing models and calling attention to anomalies. This process — the “dialectic” — pops up again and again in the academic disciplines. It’s the center of how understanding works, at this stage. And the nice thing about practicing it on literature is that, more so than in history or science, the evidence is shared knowledge — it’s right in front of everyone, written out. But there are other ways literature class can be helpful to the general life of the mind. Egan also suggests that we’ll want to specially include literature that helps students understand complex ideas. Camus, Orwell, Borges, Calvino might be particularly helpful here… and I imagine that genres like science fiction and magical realism might be particularly useful, too. (Note, though, that once again none of this requires a radical remaking of the curriculum, or of the canon of texts that we traditionally assign to high schoolers.) Q: Oh yes, the canon — what does Egan have to say about the canon wars? When he wrote Educated Mind in the nineties, the long-brewing canon war was approaching its inevitable apocalyptic climax. On one side of this Plain of Megiddo were the pro-canon traditionalists, arguing that we should keep assigning the texts that had been argued over for centuries. Facing them were the anti-canon reformers, arguing the standard texts over-represented the perspective of dead white men. Onto the middle of the plain rides Egan on a white horse, who bellows above the din: “I’VE GOT A BUSLOAD OF HIGH SCHOOLERS WHO WANTS TO JOIN IN, EVERYONE OKAY WITH THAT?” To do so, he says, we need to give students the arguments from both sides. So, for example, bell hooks, Edward Said, and China Achebe should be on the syllabus, as should Allan Bloom, Mortimer Adler, and Diane Ravitch. And of course they should actually read the texts cherished by both sides, too, so they can argue better. High school history How could entering the big fights help us reinvent high school history? First, we might look for dueling histories. It’s time for students to get into historiography and understand that history isn’t just what happened, it’s something we make. We might help kids read chapters from Howard Zinn’s socialist history of America alongside the corresponding chapters from Paul Johnson’s conservative history of America. How could big questions help? We want to help students see how various people have disagreed over some of the big questions of what human history is, at its most basic. We can have them compare Steven Pinker’s theory of civilization’s progress (Better Angels of our Nature) with Yuvah Noah Harari’s theory of civilization’s woes (Sapiens). We could have them compare so-and-so’s account of human history as an ever-expanding unlatching of energy sources with Robert Wright’s account of human history as unlatching more and more positive-sum games (Nonzero). What role could the lure of certainty play? To help them grow their skills at finding anomalies, we might help them work through pseudo-histories and conspiracy theories. Q: Conspiracy theories! Oh, come now, you’re playing with fire. Well, the world is on fire. Our students will spend the rest of their lives encountering terrible-but-beguiling arguments about how the world works; if we don’t prepare them for those, what have we been doing? So we should introduce arguments that the Moon landing was a hoax, that the Illuminati founded America, that aliens built the pyramids, and so on. At no point can we demean students for falling for any of these theories — the job of a teacher at this stage, Egan writes, is to support students in their reasoning even when their beliefs are offensive and stupid, gradually offering anomalies. There’s no way out of bad theories except through them. By the time students graduate, we want them to have wrestled with terrible ideas and — for a while — lost. They need to experience what it’s like to change their minds about something they felt strongly about. They need to viscerally realize, in Feynman’s famous phrase, “The first principle is that you must not fool yourself and you are the easiest person to fool.” High school natural science How could entering the big fights reinvent high school science? At present, so much of the high school science curriculum — especially “honors” classes — is oriented toward helping amass details. (The same is true of 100-level university classes, which famously “survey” the field to prepare for more advanced studies. I always thought this was stupid — of the huge lecture hall of students in my Geology 100 class, how many went on to take even a second course?) The meaty debates that propel science forward are held back. Egan complains: “The more general and speculative theories in any discipline are treated like an unconventional and disreputable relation who, even though the children find her exciting and entertaining, must be kept hidden from view, her very existence denied as long as possible”. This is a stupid approach — students with an adventurous bent are convinced that science isn’t for them. Egan proposes, simply, that we flip this, and organize high school science classes around the big debates. We shouldn’t be ashamed at how, well, adolescent this might look: “the dramatic, speculative, and contentious theories will be up-front in the early years of the [high school] curriculum”. What might those be? Egan doesn’t give a list, but we can spitball some: instead of explaining what “matter” is from the top down, a physics class could problematize “matter” by following the debates over the nature of dark matter and dark energy, and by becoming familiarized with the various interpretations of quantum mechanics
Pixel 8 Pro

Pixel 8 Pro is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2025 and October 24, 2025. The archive places it in contexts such as "despite being shot with a Pixel 8 Pro using the best settings". It most often appears alongside A Ordem, Abraham Lincoln, ACX.

Reference entry
Pixel 8 Pro
Mention count
1
Issue count
1
First seen
October 24, 2025
Last seen
October 24, 2025
October 24, 2025 · Original source
Why am I so confident about this? Because I’ve often played with that kind of effect using devices that struggle to adjust brightness under similar conditions. Want a more dramatic sky? Just lower the camera a bit. Even with more modern devices, my experience is that taking pictures (or even more so, filming) at sunset often results in odd brightness corrections and even strange color shifts. I filmed a video this summer during unusual twilight weather, and the result was totally weird, despite being shot with a Pixel 8 Pro using the best settings.
plink

plink is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "plink is software you can use to calculate scores based on genotype". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
plink
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
And plink is software you can use to calculate scores based on genotype.
Polly Pocket

Polly Pocket is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "may include Polly Pocket". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
Polly Pocket
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
polygala tenuifolia

polygala tenuifolia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Less-well-studed but promising supplements including Zembrin and polygala tenuifolia". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
polygala tenuifolia
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
Polygala tenuifolia is a Chinese herb. It is under investigation as a rapid-onset depression treatment that may act on NMDA and AMPA receptors, perhaps similarly to the rapid-onset depression treatment of ketamine. It is still extremely experimental and has few studies in support, but early anecdotal evidence is optimistic. The only really credible source for it right now is here, and the recommended dose is 100 mg three times a day. Even more than other substances on here, this one should be considered experimental and not left as the mainstay of important depression treatment.
PowerPoint

PowerPoint is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 01, 2025 and April 01, 2025. The archive places it in contexts such as "write another PowerPoint slide again". It most often appears alongside Afghanistan, AI, anime.

Reference entry
PowerPoint
Mention count
1
Issue count
1
First seen
April 01, 2025
Last seen
April 01, 2025
April 01, 2025 · Original source
This has hitherto been slow enough to tolerate, but strong AI will make it all worse. You will see wonders beyond your imagination, nod, think “that’s a cool wonder”, and become inured to it. In the process, everything else that matters will wither away. If you get meaning from your job, the AI will take your job. If you get meaning from helping others, the AI will end poverty and cure cancer without your help. If you get meaning from your community, too bad - your friends are hanging out with AI sexbots now. It’ll all be great, of course. The AI taking your job means you never have to write another PowerPoint slide again; you can sit at the beach all day, sipping tropical cocktails. The AI ending poverty will be the best thing that ever happened. The sexbots . . . do you really need me to keep selling you on these? It’ll all be perfect forever, and you’ll spend the whole time writing Substack articles with titles like “Can We As A Society Finally Shut Up About The Wonders Beyond Our Imagination?” and “Do The Wrong Type Of People Like Cancer Cures Too Much?”
pramipexole

pramipexole is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 16, 2022 and November 16, 2022. The archive places it in contexts such as "after starting the pramipexole". It most often appears alongside @AutismCapital, Adderall, ADHD.

Reference entry
pramipexole
Mention count
1
Issue count
1
First seen
November 16, 2022
Last seen
November 16, 2022
November 16, 2022 · Original source
Does this mean that Emsam definitely wasn’t involved? Not exactly. “Gave someone a gambling disorder” is an overly binary way of saying “shifted someone’s brain’s risk curves6 a lot”. One of the case reports of antiparkinsonian-induced gambling was a “54-year-old, married pastor” who began gambling large sums daily after starting the pramipexole. It probably takes a lot of risk-curve-shifting to get a 54-year-old married pastor to go to Vegas and blow all of his savings. But if you’re already a cryptocurrency trader, maybe it only takes a tiny amount of risk-curve-shifting to turn you into a cryptocurrency trader who makes riskier trades. Maybe selegiline only shifts your risk curve a lot 0.001% of the time, but it shifts it a tiny bit more often than that.
PreSeed

PreSeed is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 30, 2025 and October 30, 2025. The archive places it in contexts such as "Silicon Valley sperm donor search startup called - of course - PreSeed". It most often appears alongside 767 AD, @Scientific_Bird, ACX.

Reference entry
PreSeed
Mention count
1
Issue count
1
First seen
October 30, 2025
Last seen
October 30, 2025
October 30, 2025 · Original source
51: Silicon Valley sperm donor search startup called - of course - PreSeed.
Pringles

Pringles is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2025 and August 08, 2025. The archive places it in contexts such as "Pringles minted from the very same potato flakes that go into IMPs". It most often appears alongside Ainu, Altiplano, American cheese.

Reference entry
Pringles
Mention count
1
Issue count
1
First seen
August 08, 2025
Last seen
August 08, 2025
August 08, 2025 · Original source
As a child I hated mashed potatoes, despite his evangelization of them. I too was a picky eater growing up, but I would occasionally attempt to see what he saw in his beloved spuds. Whenever I tried a bite, the texture disgusted me: a gritty gruel of salty flakes coated with the oleic pall of margarine. The flavor reminded me of stale Pringles. I checked back once every couple years, but was repulsed by them every time.
The other foods in this category are obvious - McNuggets reconstituted out of pink slime, American cheese product, instant coffee, deli ham, Pringles minted from the very same potato flakes that go into IMPs. We’ve even developed a whole new health scare over them: “Ultra processed foods”2 are as demonized now as butter and whole milk were when my parents were young.
prismatext.com

prismatext.com is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "language learning, that seems to already exist as a company: prismatext.com". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
prismatext.com
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
4 (Language learning technique): Several people linked to groups that are already trying this. I was most excited by Weeve, but there’s also Prismatext, The Adventures Di Pinocchio, and DonQuixote.fun. If any of you try any of those, let me know how it goes.
Re: language learning, that seems to already exist as a company: prismatext.com
Pro Action Rod

Pro Action Rod is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 24, 2022 and May 24, 2022. The archive places it in contexts such as "Perez Combat Inc, makers of the Pro Action Rod". It most often appears alongside #Abolitionist, #AntiNazi, #antiwar.

Reference entry
Pro Action Rod
Mention count
1
Issue count
1
First seen
May 24, 2022
Last seen
May 24, 2022
May 24, 2022 · Original source
Like every other proud diverse minority conservative, he has a business: Perez Combat Inc, makers of the Pro Action Rod:
propofol

propofol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 09, 2023 and August 09, 2023. The archive places it in contexts such as "brain desynchronisation has been observed when people are given anaesthetic doses of propofol". It most often appears alongside @data_depot, @StefanFSchubert, AI Snake Oil blog.

Reference entry
propofol
Mention count
1
Issue count
1
First seen
August 09, 2023
Last seen
August 09, 2023
August 09, 2023 · Original source
[O]verall brain synchronisation was reduced. Usually, certain parts of the brain are active at the same time, firing electrically together. ‘One part of the brain has a relationship with the activity of another part of the brain in a way that’s predictable,’ Laukkonen says. These parts of the brain are usually communicating with each other, but the new findings suggest that during nirodha-samāpatti that feature quietens down. Similar brain desynchronisation has been observed when people are given anaesthetic doses of propofol or ketamine, but not during sleep.
propranolol

propranolol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 16, 2022 and March 16, 2022. The archive places it in contexts such as "propranolol (the first drug discovered in the target-based way) wasn't patented until 1962". It most often appears alongside 5α-reductase inhibitor, A Mindful Monkey, ALLO.

Reference entry
propranolol
Mention count
1
Issue count
1
First seen
March 16, 2022
Last seen
March 16, 2022
March 16, 2022 · Original source
I doubt that the concept of "positive allosteric modulator" existed in 1955 when chlordiazepoxide was invented; in those days drugs were discovered by making random chemicals and feeding them to animals to see what happened. The receptor theory of medchem (i.e. that drugs have a specific biochemical target in the body) is generally credited to James Black and his fellow Nobel laureates, and propranolol (the first drug discovered in the target-based way) wasn't patented until 1962.
pterostilbene

pterostilbene is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 02, 2021 and December 02, 2021. The archive places it in contexts such as "some people are now experimenting with pterostilbene, a more bioavailable resveratrol relative". It most often appears alongside Alexandre Gueniot, Algernon’s Law, Alzheimers.

Reference entry
pterostilbene
Mention count
1
Issue count
1
First seen
December 02, 2021
Last seen
December 02, 2021
December 02, 2021 · Original source
But there are two other pills that might work. One is resveratrol, a chemical found in red wine (though not in high enough doses to be meaningful for sirtuin activation). Resveratrol definitely activates sirtuins in test tubes, and seems to be good for lab animals: some of them live longer on it, others at least seem healthier. But the lab animal studies were never 100% conclusive, and arguably humans absorb it too poorly to be able to get an effective dose (I’m confused about some details here, like whether animals absorb it better, or whether IV formulations would work). There was a big mess surrounding claims by resveratrol supplement companies, whether their products might have worked or whether they couldn’t possibly have. David Sinclair was caught in the middle and got accused of being a Big Resveratrol shill, and scientific opinion seems to have settled as most against it. I think some people are now experimenting with pterostilbene, a more bioavailable resveratrol relative.
Pullman

Pullman is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2023 and June 23, 2023. The archive places it in contexts such as "Pullman made train cars". It most often appears alongside 1965, 1968 Summer Olympics, 2000 election.

Reference entry
Pullman
Mention count
1
Issue count
1
First seen
June 23, 2023
Last seen
June 23, 2023
June 23, 2023 · Original source
So he started a new organization dedicated to doing just that: the Center for the Study of Responsive Law. His newfound fame enabled him to recruit a prestigious group of young lawyers from elite schools, including President Taft’s great-grandson and Ed Cox, who married Richard Nixon’s daughter while working for Nader. “It’s like you’re looking at the names of the Pullman cars,” said one of Nader’s early employees, in a joke that today requires so much explanation I almost regret including it in this piece9.
Pullman made train cars; in the days before widespread air-travel, the super-rich would have private luxury cars with their names on them.
PupilScreen

PupilScreen is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 18, 2025 and June 18, 2025. The archive places it in contexts such as "development of our application, PupilScreen". It most often appears alongside 1DaySooner, Aatu Koskensilta, acanthamoeba keratitis.

Reference entry
PupilScreen
Mention count
1
Issue count
1
First seen
June 18, 2025
Last seen
June 18, 2025
June 18, 2025 · Original source
Codebuff, an AI coding startup I probably can’t take full credit for all of this just from giving them $20K in seed funding, but I continue to appreciate everything they do for this community and the world. 35: Further S’s Political Career This person didn’t win their election, but has since pivoted to AI safety and works in a well-regarded AI policy think tank. 36: Seeds Of Science, A Journal Of Non-Traditional Research No update received, but this was a public journal and it is easy to follow their work, see their website and Substack. They published two dozen articles of widely varying quality through 2023 and 2024, then closed in 2025. A remnant of the original vision survives as a science blogging aggregator. This was about my median expectation for this grant, but it was very inexpensive and I decided to take a chance on it anyway. 37: Good Science Project, Working To Improve Federal Science Funding No update received, but they have a public Substack discussing their progress. Their proposals for NIH reform have influenced Congress and made government agencies pay more attention to scientific integrity. 38: Advising Developing Countries On How To Grow Their Economies With our initial ACX grant, we piloted the Growth Teams model in Rwanda, helping the government jumpstart the export-oriented call center (BPO) industry. Since 2022, that effort has contributed to the creation of 2,000 formal jobs and the emergence of some of the country’s largest private employers. We’ve since expanded to Tanzania, Malawi, and the Indian states of Goa and Meghalaya. To refocus the global development discourse on broad-based economic growth, we co-organized the Growth Summit with the Center for Global Development and the Charter Cities Institute, and have published articles in leading outlets including Stanford Social Innovation Review, ProMarket, and the Global Prosperity Institute. Our work has attracted support from Open Philanthropy, Schmidt Futures, and Mulago Foundation, and our advisors now include economists Lant Pritchett, Stefan Dercon, and Kunal Sen. 39: Help Luca De Leo Get Started In AI Safety Research No update received, but Luca now runs the AI safety group at the University of Buenos Aires, Argentina. 40: Typist For Saharon Shelah This was another ACXG+ Grant, funded by an anonymous outside funder and not listed in the original announcement. Saharon is a prolific and influential Israeli mathematician, but many of his discoveries are hand-written in an unpublishable format. This grant funded a typist to help make his results suitable for publication. According to this page, they have made over fifty new papers and preprints available. Second Cohort: One Year Updates 41: Lead-Acid Battery Recycling In Nigeria The Nigeria field research was a major success. We spent most of September doing field research in multiple major cities in Nigeria, and got a good sense of the used lead-acid battery supply chain. This field research served as the foundation for expanding our project, and has been very impactful in shaping our ongoing research. We published our findings from Nigeria, which were shared with Nigerian government regulators and global NGOs working on lead poisoning. The grant also gave us the on-the-ground experience we needed to both fully understand and credibly engage with groups, both in Nigeria and globally, on the ULAB issue. In the meantime, beyond continued research, we’ve also launched a dashboard (trade.leadbatteries.org) for analyzing global lead trade data. Right now, we’re: Launching two studies (one RCT, one environmental analysis) in Nigeria in collaboration with local universities to develop a more rigorous understanding of lead pollution due to low-standard ULAB recycling in Nigeria Collaborating with a non-profit incubator to launch an NGO focused on demand-side solutions Beginning a partnership with a West African environmental regulator to scale cheap air monitoring technology to quickly identify and reduce lead pollution from low-standard smelting If any of this sounds interesting to you, please sign up for our Substack (leadbatteries.substack.com) or send us an email at hugosmith@uchicago.edu! 42: Compensation For Kidney Donors The End Kidney Deaths Act (H.R. 2687 / EKDA) is a groundbreaking ten-year pilot program designed to save lives and reduce healthcare costs. It provides a refundable tax credit of $10,000 per year for five years, a total of $50,000, to living kidney donors who donate to a stranger, helping those who’ve waited the longest on the transplant list. Between 2010 and 2021, 100,000 Americans died while qualified and waiting for a kidney. The EKDA aims to change that trajectory. Within ten years of its passage, up to 100,000 Americans could receive a life-saving living donor kidney which typically lasts twice as long as a deceased donor kidney. This would not only save lives but also save taxpayers up to $37 billion. The legislation has been reintroduced in the House, and we have a committed Republican Senate lead. Now, we need a Democratic Senator to co-lead and help move this bipartisan effort forward. Time is short, and we are racing to pass the bill this Congressional session. 36 organizations already support the EKDA. Join the movement and help end preventable kidney deaths. Visit EndKidneyDeaths.org to help us get to the finish line. Elaine and her org have been working extremely hard on this; you can read a Vox article on their campaign here. If you want to sign up for her email list and get updates any time there is a representative you can contact or meeting you can join in, go here. 43: Genetic Hack To Prevent Suffering In the estimate of multiple team members, the ACX grant was “worth it” - it likely had a counterfactual net positive impact, even though we had to pivot from our initial fast-track plans for developing the precision anti-suffering therapy. We identify three primary streams of value: a) reducing uncertainty in the emerging field through early exploratory research, helping with the identification of dead ends and promising R&D trajectories; b) a wide range of downstream effects (beyond the “raising awareness” cliché), including talent mobilization and rekindled interest in suffering abolitionism as a distinct cause area; and c) certain developments that cannot yet be publicly disclosed. In December 2024, Marcin Kowrygo (Acting CEO & volunteering contributor), David Pearce (Director of Bioethics), Aatu Koskensilta (President), and a few other team members decided to leave The Far Out Initiative. They look forward to collaborating and applying their experience to advance the suffering abolitionist lineage in the spirit of open science, public good, and thoughtfully decentralized governance. Feel free to reach out to us at suffab at protonmail dot com to discuss collaboration opportunities! I wrote a post profiling the Far Out Initiative here. Unfortunately there were some internal disagreements, and the people ACX Grants was closest to left the organization. I plan to continue to monitor whatever they do next. 44: Advocate For Pandemic Response Team At FDA This team prefers has asked me not to discuss their progress publicly, but you can probably guess what their lives are like right now, and your guess would be correct. 45: Anti-Mosquito Drones We developed a cheap sonar that is able to detect, track and classify the ultrasonic echoes of mosquito wings at more than three meters. I believe it’s a world first! We also have control algorithms that take the sonar data and output control commands that both ram into mosquitoes and avoid the walls of a simulated environment. Our current work is on integrating both components on a real drone, and we expect to be able to kill mosquitoes by June. We’ve also made an internal impact study (napkin-sized) that shows we’ll be more cost-effective than ITNs in urban to periurban environments. So, we’re super excited with what comes next and can’t wait to share the videos of our first interceptions! More information [in the video below] and on our website, https://tornyol.com 46: Tarbell Fellowship For AI Journalism No update received, but they have a public website. I can’t find the Voices program in particular, but the overall fellowship completed their first class of seven fellows and is working on their second. 47: Germicidal UV Lamp Study The research has successfully demonstrated the ability of off the shelf ozone scrubbers to mitigate the ozone production of far-UVC lamps, is now available as a preprint (https://chemrxiv.org/engage/chemrxiv/article-details/67e4cde76dde43c9084d88b7). The paper has been submitted for publication and is currently undergoing peer review. Any ideas you have for potential funders we can approach to help execute our six-year plan to accelerate far-UVC would be appreciated https://blueprintbiosecurity.org/introducing-project-air/ 48: Technological Solutions To Animal Welfare Challenges Directly because of Innovate Animal Ag's work, the first U.S. egg producer publicly announced in the New York Times their adoption of in-ovo sexing technology, eliminating the need to cull day-old male chicks. The initial in-ovo sexing machine began operating in the U.S. at the end of 2024, with the first eggs from these hens expected on shelves in mid-2025. External evaluations estimate our work accelerated U.S. adoption of this technology by over seven years, meaning that once fully implemented, more than 2 billion chicks will have been spared. In addition to continuing to support the rollout of in-ovo sexing in the US and globally, we're now exploring other technologies and paths to impact. Current promising projects include developing humane slaughter methods for fish and advocating for USDA approval of a poultry vaccine against bird flu. They add: If you ever meet folks that are interested animal welfare and are partial to more technocratic and practical solutions, please continue to pass them our way, or connect them directly to me. 49: Assurance Contract Website www.Spartacus.app is an ACX grantee that created a platform to help solve coordination and collective action problems. It enables the creation of campaigns that build critical mass through conditional commitments, which only activate when a sufficient number of people join, converting risk and uncertainty into a higher probability of successful outcomes. They are currently facilitating several projects that leverage conditional commitments, including a dominant assurance contract interface for fashion pop-ups, accelerating a community business association's membership drive, and helping an AI safety organization organize petitions and events, among others. They have pivoted from an emphasis on high-stakes coordination problems requiring anonymity (because they occur too infrequently) to a broader range of more common use cases and have successfully run small-scale campaigns, but are still working toward product-market fit. Despite resource constraints and split time commitments that have impeded faster progress, they remain dedicated to the project's growth and success. You can follow its progress on X or Substack, or email Jordan directly here. 50: Cause Prioritization @ Center For Exploratory Altruism Research Moderately good progress on a salt reduction policy advocacy project we funded; informal commitments have been made by the Ministry of Health, and we're awaiting the publication of a formal administrative order. The official description sounds maximally generic, but this is an EA charity with a broad mandate whose current thesis is that dietary guidelines in developing countries can have outsized effects in saving lives. They’re making some progress on a salt reduction campaign in a developing country they prefer not to name publicly. 51: Mark Webb Studying Land Reform The purpose of this project was to identify specific farmland that could be acquired and transferred to the farmers already working the land. This has been difficult to achieve. I have been able to connect with other charities and landless farmers, and was able to interview a number of people about what their situation looks like, as well as what it would look like to them personally if they owned, rather than rented, their farmland. All this was immensely helpful in pushing this long-term project forward, even if I was unable to identify a specific plot of land that could be used to try the experiment. I intend to continue this project. If you have any insights or connections, I am interested. 52: More AI Advocacy In Australia Good Ancestors is focused on AI safety policy in Australia. Middle powers might be a useful path to influence as the US and China focus on racing, rather than safety. The ACX grant helped us give testimony about AI safety to the Australian Senate alongside Google, Microsoft and Facebook (We were the only nonprofit to give oral evidence to the inquiry. We also engaged government on other AI-related issues, including cybersecurity, biosecurity, consumer law and automated decision making (https://www.goodancestors.org.au/ai-safety). We’re currently working to inform voters about where parties stand on AI safety for the election, ahead of engaging on a likely Australian AI Act in 2025 (https://www.australiansforaisafety.com.au/). This is the same Australian lobbying organization we founded in Year 1, after a change in name and leadership. I continue to be excited about AI safety in middle-tier countries for a few reasons. First, these countries have some power in international organizations to set international standards. Second, companies will usually comply with any not-excessively-burdensome regulation set by any country with a significant market. Third, AI safety is underfunded by the standard of government programs, so Australia setting up a national AI Safety Institute would significantly expand the field. It’s kind of crazy that ACX Grants tier levels of money can have significant effects at this scale, but GA continues to do a great job and we continue to be proud to support them. 53: Campus For African School Of Economics At Zanzibar Charter City The ACX grant helped launch the first research center at the African School of Economics-Zanzibar, which is a main anchor of the Fumba Town charter city project in Zanzibar. This research center is called the Africa Urban Lab (AUL), focused on rapid urbanization across Africa. The AUL launched its first Diploma program in Urban Development with 38 students in our first cohort (now graduated!), including mayors, and deputy mayor, a director of a national Ministry of urban development, and many others. We published our research framing papers for the AUL's research agenda. We raised funding to launch an Urban Expansion Program that's now selecting 15 African cities to support in implementing urban expansion planning on the urban periphery. We held two Public Talks by renowned cities scholars and practitioners. We received additional funding from Emergent Ventures and from the Templeton Foundation. And we've partnered with 8 universities across the region, and with one of these universities (Ardhi) we'll be working with them to update their urban planning and urban economics curriculum (amplifying AUL's impact beyond our own organization). A longer update from end of 2024 is here: https://www.aul.city/blog/reflecting-on-africa-urban-lab-s-inaugural-year-2024-highlights) 54: Online Training Program For Health Workers In Developing Countries To date, over 11,000 health workers in Nigeria have completed our course on basic, life-saving newborn care. ACX funding was catalytic for helping us secure government approvals and complete an evaluation of the impact of our training on health workers' clinical practices. The evaluation shows that birth attendants provide better birth care after taking the course. We fed the evaluation results into an updated model, which suggests the program is 24 times more cost-effective than direct cash transfers (a widely recognized benchmark for cost-effectiveness). The program is likely to become even more cost-effective as we scale up. https://healthlearn.org/blog/updated-impact-model 55: Smartphone Pupillometry To Diagnose Neurological Conditions We have continued to expand our work in the smartphone pupillometry space and the development of our application, PupilScreen (https://www.apertur.ai/). We have expanded our pilot/research program to include new sites across the United States (Missouri, New Jersey, Kentucky, USAC racing, PitFit driver performance training in Indiana) and the world (Nepal, Taiwan, South Africa). We continue to publish at the leading edge of the pupillometry literature as well looking at concussion (https://neuro.jmir.org/2024/1/e58398 and https://pubmed.ncbi.nlm.nih.gov/39682632/), cerebral vasospasm (https://pubmed.ncbi.nlm.nih.gov/39128501/), and stroke (https://pubmed.ncbi.nlm.nih.gov/39674431/ and https://pubmed.ncbi.nlm.nih.gov/39561861/). Currently, we are raising a $3 million seed round via a SAFE to fund the expansion of our work into the hands of healthcare workers and the general public. We will first focus on traumatic brain injury for clinical use and develop a neuro-monitoring wellness application utilizing our technology for the general public. They add: “We would welcome connections to anyone that you think might be interested in supporting our work further by investing in our $3M seed round of funding.” 56: Mike Saint-Antoine’s Biology Tutorial Videos Since getting the grant, I've continued to make Youtube tutorials as planned. One series that I'm especially proud of is about how to make a neural network in the Julia programming language completely from scratch, with no imports, up to the point of being able to solve MNIST (https://www.youtube.com/playlist?list=PLWVKUEZ25V97tNULapu07DhWv6_W4NfpE). Also, a college student in Pakistan came across my videos and invited me to give a virtual Zoom-lecture to her department, so I ended up teaching a 6-hour "Python-for-Biologists" workshop to more than a hundred college students in Pakistan over Zoom. So that was pretty awesome. Also, lately I've been teaching some in-person classes too, mostly at Fractal University in NYC, and I also recently organized a day-long, in-person Beginner Python class for people in my local area (Philly suburbs) who wanted to learn some basic programming. I'm having a lot of fun with this project, and am grateful to Scott and the grant funders for their generosity! 57: Conceptual Boundaries Workshop On AI Safety The workshop was completed successfully; you can read a writeup here. 58: Apart Research To Incubate AI Safety Scientists No update received, but they have a public website, and you can see their impact metrics here. They seem to be in urgent need of more funding. 59: Primer On How To Achieve Political Change No update received and I can’t find anything about this. 60: Research IVF Clinic Success Rates We've built a predictive model that estimates the odds of having a child at different IVF clinics across the country while controlling for factors like patient age and infertility differences that can falsely make some clinics look better than others. We found that an average patient can increase their odds of having a kid by 43% just by going to a top 10% clinic. Patients unlucky enough to go to a bottom 10% clinic will reduce their odds of having a kid by 40%. Next month, we're adding several more clinics, 2023 data, additional procedural controls, and donor/gestational carrier models, which should push our accuracy beyond state-of-the-art models in this space and better isolate clinic impact on patient outcomes. We've launched ivf.clinic, a website where patients can access personalized IVF reports and browse our clinic rankings (though we're still squashing some bugs). Currently, we're expanding our research to include comprehensive insurance coverage and pricing data across clinics nationwide. If anyone has insights on automating the collection of IVF clinic pricing information, I'd love to hear from you at scelarek@gmail.com. 61: Replicate Study On Brain Wave Synchronization For Speeding Learning We have acquired and configured the OpenBCI UltraCortex Mark IV 8-channel EEG headset and a clinical-grade Biosemi 32-channel EEG system. We’ve implemented the required components for the experimental pipeline (computing alpha from EEG, flashing bright white light, presenting stimulus images). We are currently putting them together into a single system that we’ll use to collect the data from several participants. We are aiming to gather data on several participants in late June / early July and complete the pilot of the replication in July 2025. If you’d like to be a participant in the study, [they might announce a link once they have it]. 62: Advocate Repeal Of Interstate Runaway Compact No update received and I can’t find anything about this. 63: Animal Welfare (Especially Fish) In Turkiye Future For Fish asks companies to sign up to FFF's fish welfare commitment, which requires producers to certify their facilities and enforce specific standards for stocking density and harvest. Luckyfish, İlknak, Divan (35 restaurants, 17 hotels) and NG Hotels (5 hotels) have signed and published FFF's fish welfare commitment with İlknak publishing the commitment on their website. Kılıç published its first sustainability report detailing fish welfare policies, including enforcing a maximum stocking density of 10 kg/m³ and confirmation of electrical stunning practices. Longer version with some caveats: https://manifund.org/projects/improving-fish-w From the longer document, these commitments involve things like reducing overcrowding, or stunning fish before killing them. Over 30 million fish were affected just from their single largest commitment, and they say 100 fish are helped per dollar spent. 64: More Georgism Advocacy Lars and Will used the 2021 grant to co-found ValueBase. Will remained with the company, and Lars left to do advocacy work at the Center For Land Economics. Here’s their summary of how things are going: [Our] organization transitioned leadership with Greg Miller, a former Program Analyst at the US Department of Housing and Urban Development, and Lars Doucet, author of Land is A Big Deal and Co-Founder of Valuebase, working full time and Joe Caissie stepping aside. This transition happened naturally as the next career transition for each respective person. Since then, progress has been made on pushing forward legislation. Maryland had two bills introduced to give Baltimore and counties the ability to enact split-rate taxes. One of the bills passed the state senate and would allow Baltimore to enact land value taxes within one mile of rail corridors–this contains 50% of Baltimore’s land value. However, the legislative session ended. We expect the bill to revive next session. The Center for Land Economics has been actively working to help efforts to get this bill passed the line. At the same time, we have uncovered systematic undervaluing of vacant land in assessments. We are writing a report on the assessment issues in Maryland with actionable steps to resolve them.
QRiosity

QRiosity is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 18, 2024 and April 18, 2024. The archive places it in contexts such as "I run QRiosity, a browser with native QR code support". It most often appears alongside Africa, AI Circle, Bay Area.

Reference entry
QRiosity
Mention count
1
Issue count
1
First seen
April 18, 2024
Last seen
April 18, 2024
April 18, 2024 · Original source
“I run QRiosity, a browser with native QR code support. Just click on a QR image, and it will take you to the website!”
Qsymia

Qsymia is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 24, 2022 and November 24, 2022. The archive places it in contexts such as "Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance". It most often appears alongside ACE inhibitors, ACE inhibitors, Adderall.

Reference entry
Qsymia
Mention count
1
Issue count
1
First seen
November 24, 2022
Last seen
November 24, 2022
November 24, 2022 · Original source
“Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
quinacrine

quinacrine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 12, 2024 and July 12, 2024. The archive places it in contexts such as "Prusiner experimented with quinacrine, the malaria cure, as a potential CJD treatment". It most often appears alongside 1980s, 1989, 1990s.

Reference entry
quinacrine
Mention count
1
Issue count
1
First seen
July 12, 2024
Last seen
July 12, 2024
July 12, 2024 · Original source
Prusiner experimented with quinacrine, the malaria cure, as a potential CJD treatment. He gave a bunch of it to a young woman whose father heard about his research. It stopped her symptoms from progressing – and exploded her liver. “By now, more than three hundred prion disease sufferers have tried quinacrine and, according to Graham Steel, the head of the CJD Alliance in the United Kingdom, “they’re all dead.””
racetams

racetams is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2021 and July 21, 2021. The archive places it in contexts such as "Patients usually get prescribed nootropics (glycine, racetams)". It most often appears alongside 9/11, ACOUP, Adderall.

Reference entry
racetams
Mention count
1
Issue count
1
First seen
July 21, 2021
Last seen
July 21, 2021
July 21, 2021 · Original source
Living in Russia, I can say that ADHD (translated as СДВГ) is less recognized by the psychiatry community here because of its unclear aetiology. Doctors usually refuse to treat the patients in the absence of dangerous symptoms, and state the diagnosis as "organic nervous system disorder", "psychoorganic syndrome" or indeed "neurasthenia". Adderall and Ritalin are illegal drugs here. Patients usually get prescribed nootropics (glycine, racetams) and adrenaline reuptake inhibitors (atomoxetine).
ranitidine

ranitidine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 23, 2021 and November 23, 2021. The archive places it in contexts such as "the ranitidine withdrawal". It most often appears alongside Andrew, clinicaltrials.gov, Dan Elton.

Reference entry
ranitidine
Mention count
1
Issue count
1
First seen
November 23, 2021
Last seen
November 23, 2021
November 23, 2021 · Original source
Note that this really only applies to new chemical entities; people have been manufacturing fluvoxamine for years and its probably well understood by now. Not always true though; we saw a worst-case situation recently with the ranitidine withdrawal: a medicine that some reasonably healthy people take every day of their lives was shown to be contaminated with small amounts of a nasty carcinogen. If Pfizer happened to have some gaps in their understanding for the Paxlovid process, the FDA might go easy on them as dying of Covid now is worse than a slightly increased risk of cancer in the future, but it takes time to review all of these risks and make a justified decision.
RasPi Zero

RasPi Zero is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "An off-the-shelf microcontroller board (e.g. RasPi Zero, Arduino) should be sufficient for that". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
RasPi Zero
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
I think getting to a millisecond timing is not all that difficult. An off-the-shelf microcontroller board (e.g. RasPi Zero, Arduino) should be sufficient for that, no need for FPGAs.
RedCoin

RedCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 12, 2021 and February 12, 2021. The archive places it in contexts such as "RedCoin is notable for its reverse-proof-of-stake". It most often appears alongside BuffyCoin, CAPTCHA, Catholic Church.

Reference entry
RedCoin
Mention count
1
Issue count
1
First seen
February 12, 2021
Last seen
February 12, 2021
February 12, 2021 · Original source
RedCoin: Karl Marx always said that communism would be a non-hierarchical economic system that prospered after the state withered away. A group of Marxist intellectuals took the obvious next step and made it an altcoin. RedCoin is notable for its reverse-proof-of-stake; you get more RedCoin in proportion to how little RedCoin you have right now, ensuring that all wallets naturally tend toward an equal amount. You can't do decentralized finance on RedCoin, but you can do decentralized linear programming calculations to determine the optimal allocation of goods in a planned economy.
Reddit

Reddit is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 06, 2022 and April 06, 2022. The archive places it in contexts such as "more social media (Instagram, Reddit)". It most often appears alongside America, American consulate, Attorney General.

Reference entry
Reddit
Mention count
1
Issue count
1
First seen
April 06, 2022
Last seen
April 06, 2022
April 06, 2022 · Original source
But Xi’s main target has been the Internet. Facebook, Google, YouTube, and Twitter were already blocked when he took power, but he added more search engines (including Bing and DuckDuckGo), more social media (Instagram, Reddit), foreign news (eg BBC, NYT, WaPo, the Economist), and even Wikipedia. This has been bad for business (China’s Internet “ranks ninety-first in the world” and is getting worse, and foreign businesses list difficulty using the Internet as one of their top reasons for not expanding into China more), but Xi thinks it’s a worthwhile tradeoff.
remdesevir

remdesevir is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 22, 2025 and May 22, 2025. The archive places it in contexts such as "What about the alternative claim - that it wasn’t COVID that caused the extra deaths, but various treatments - ventilators, remdesevir, vaccines?"; "various treatments - ventilators, remdesevir, vaccines?". It most often appears alongside 2022 ACX survey, CDC, census.gov.

Reference entry
remdesevir
Mention count
1
Issue count
1
First seen
May 22, 2025
Last seen
May 22, 2025
May 22, 2025 · Original source
I think this disproves the claim that it was just normal deaths being reported as COVID deaths. What about the alternative claim - that it wasn’t COVID that caused the extra deaths, but various treatments - ventilators, remdesevir, vaccines?
Research Retraction Insurance

Research Retraction Insurance is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "developing a new financial insurance product for academic research, “Research Retraction Insurance” or “RRI”". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#99: Research Retraction Insurance To Ensure Retractions Get Publicized I'm Christopher Akin, and am developing a new financial insurance product for academic research, “Research Retraction Insurance” or “RRI”. RRI is a financial insurance product that pays out to promote new findings and retractions when earlier findings are later proven false. Academia does not equally promote scientific findings when they prove false as when they are originally announced. We see this juxtaposition between the grand public declarations of scientific success and pin drop retractions. We see this is the current replication crisis of ‘classical’ results in the social sciences. RRI will help resolve the current system limitations of professional accountability, limited transparency, the likelihood of learning equally from mistakes, and an ill-informed public holding on to false findings. RRI payouts are earmarked to publicize later research findings that falsify early pronouncements, and the receiver of research funding will voluntarily, or likely be required by funders, purchase the RRI. Researchers only allocate pennies (~.025% of each funding dollar) on the thousands of funding dollars received to insure for promoting future falsifying results. The earmarked PR payouts are ~15X of premium payments, or ~4% of total received funding. I am seeking $50,000 in seed funding to conduct market research, begin RRI product development, and engage leading funding institutions in business development. Email iamchrisakin@gmail.com or visit www.linkedin.com/in/akinchristopher
resveratrol

resveratrol is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 02, 2021 and December 02, 2021. The archive places it in contexts such as "One is resveratrol, a chemical found in red wine". It most often appears alongside Alexandre Gueniot, Algernon’s Law, Alzheimers.

Reference entry
resveratrol
Mention count
1
Issue count
1
First seen
December 02, 2021
Last seen
December 02, 2021
December 02, 2021 · Original source
But there are two other pills that might work. One is resveratrol, a chemical found in red wine (though not in high enough doses to be meaningful for sirtuin activation). Resveratrol definitely activates sirtuins in test tubes, and seems to be good for lab animals: some of them live longer on it, others at least seem healthier. But the lab animal studies were never 100% conclusive, and arguably humans absorb it too poorly to be able to get an effective dose (I’m confused about some details here, like whether animals absorb it better, or whether IV formulations would work). There was a big mess surrounding claims by resveratrol supplement companies, whether their products might have worked or whether they couldn’t possibly have. David Sinclair was caught in the middle and got accused of being a Big Resveratrol shill, and scientific opinion seems to have settled as most against it. I think some people are now experimenting with pterostilbene, a more bioavailable resveratrol relative.
But when David Sinclair says that resveratrol or exercise or intermittent fasting or saunas act by “mimicking calorie restriction”, is he suggesting that they will make you weak and constantly tired? If not, why not? This sounds a denial of the fundamental mTOR tradeoff: less energy expenditure in exchange for worse performance. The impression I get from Lifespan is that all of these things will both make you live longer and make you healthier. That doesn’t really make sense to me.
ribavirin

ribavirin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 01, 2023 and February 01, 2023. The archive places it in contexts such as "The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin". It most often appears alongside 2006 Ioannidis paper, ACTIV-6, Alexandros.

Reference entry
ribavirin
Mention count
1
Issue count
1
First seen
February 01, 2023
Last seen
February 01, 2023
February 01, 2023 · Original source
Carvallo said that zero people in the treatment group of his study got COVID, compared to 58% of people in the control group. This is a pretty implausibly big effect, even by the standards of other pro-ivermectin studies, although I don’t know if anyone else tried the exact same preventative protocol as Carvallo. I think this is a more nuanced story than Alexandros’ version where Buzzfeed just doesn’t know that sometimes studies happen at more than one hospital. Is fraud the best explanation? I think Alexandros thinks of Carvallo as just not keeping very good records, so he doesn’t have raw data, and probably mixed up his numbers a few times or gave false numbers, and didn’t have anything to send his collaborators when they asked. I think this is maybe possible, although it seems suspicious that he falsely said Dr. Lombardo was involved, falsely claimed the hospital involved was doing a different trial, and got very implausible results. I can imagine weird chains of events that would cause all of these things through honest misunderstandings. But they don’t seem like the best explanation. After discussing this with Alexandros, he objects to my use of the term “known fraudster”. Perhaps I should have said “highly credibly suspected fraudster” instead, although in a Bayesian sense nothing can ever be 100% and at some point plausibility shades imperceptibly into knowledge. Still, I feel like my description here was more accurate than Alexandros’, which just mentions the hospital approval issue and says nothing about any of the rest of this in a thousand word subsection about this study in particular. I did err in saying the Carvallo paper was retracted. According to the article: After BuzzFeed News raised questions about how the study’s data was collected and analyzed, a representative from the Journal of Biomedical Research and Clinical Investigation, which published the results, said late Monday, “We will remove the paper temporarily.” A link was removed from the table of contents — but was reinstated by Thursday. The journal’s explanation, provided after this story was published, was that the author “informed us that he has already provided the evidence of his study to the media.” I apologize for the error. Elalfy et al (still disagree with Alexandros) I described this as: As best I can tell, this is some kind of Egyptian trial. It might or might not be an RCT; it says stuff like “Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment”. Were they self-allocated in the sense that they got to choose? Doesn’t that mean it’s not random? Aren’t there seven days in a week? These are among the many questions that Elalfy et al do not answer for us. The control group (which they seem to think can also be called “the white group”) took zinc, paracetamol, and maybe azithromycin. The intervention group took zinc, nitazoxanide, ribavirin, and ivermectin. There were very large demographic differences between the groups of the sort which make the study unusable […] There is no primary outcome assigned, but viral clearance rates on day seven were 58% in the yellow group compared to 0% in the white group, which I guess is a strong positive result. This table looks very impressive, in terms of the experimental group doing better than the control, except that they don’t specify whether it was before the trial or after it, and at least one online commentator thinks it might have been before, in which case it’s only impressive how thoroughly they failed to randomize their groups. Overall I don’t feel bad throwing this study out. I hope it one day succeeds in returning to its home planet. In the summary post, Alexandros’ entire criticism of my coverage of this trial, one of the seven trials he focuses on as most unfairly covered and uses as the lynchpin of his argument that I am morally culpable for disastrously bad reporting, is: [Elalfy et al] are accused of incompetence for failing to randomize their groups multiple times in Scott’s piece. The paper writes in six separate places that it is not reporting on a randomized trial, amongst them on a diagram that Scott included in his own essay. Hard to imagine how else they could have made it clear. In his full post on this, he goes line by line to point out all the places they say they are non-randomized, pausing to snark about how dumb I am for not noticing each time4. But he never addresses the actual source of my confusion, which is the part of the paper where it says that: Patients were self-allocated to the treatment groups; the first 3 days of the week for the intervention arm while the other 3 days for symptomatic treatment. If this was done as described, it should be an (almost) random trial; patients who come in on Wednesdays shouldn’t systematically differ from patients who come in on Thursdays5. But in fact, it looks (assuming I am understanding a very ambiguous table correctly) like there are very large pre-existing differences between the groups, sufficient to explain the entire result. If they in fact followed their days-of-the-week protocol, and it was random as expected, then I’m misunderstanding the table seeming to show very large differences, and they have indeed found evidence for ivermectin’s efficacy. If they didn’t follow their day-of-the-week protocol and it’s non-random, then maybe I’m understanding the table correctly and their groups had large differences to begin with and the fact that they had large differences at the end of the trial doesn’t demonstrate anything about ivermectin. This is all I was trying to say in the post, and instead of having any opinion on it Alexandros just makes fun of me for saying it. I think our actual crux is that Alexandros thinks a table of big differences between the groups has to be post-treatment (based on how big the differences are), whereas I’m not sure (because it’s unclear in the study, and also because the authors describe what could be a randomization method but also go on and on about how nonrandom they are). This is why I thought it mattered how random it was! Maybe instead of mocking me for this, you can admit it’s an important and relevant question! Ghauri et al (still disagree with Alexandros) I describe this as: Pakistan, 95 patients. Nonrandom; the study compared patients who happened to be given ivermectin (along with hydroxychloroquine and azithromycin) vs. patients who were just given the latter two drugs. There’s some evidence this produced systematic differences between the two groups - for example, patients in the control group were 3x more likely to have had diarrhea (this makes sense; diarrhea is a potential ivermectin side effect, so you probably wouldn’t give it to people already struggling with this problem). Also, the control group was twice as likely to be getting corticosteroids, maybe a marker for illness severity. Primary outcome was what percent of both groups had a fever: on day 7 it was 21% of ivermectin patients vs. 65% of controls, p < 0.001. No other outcomes were reported. I don’t hate this study, but I think the nonrandom assignment (and observed systematic differences) is a pretty fatal flaw. Alexandros notes that these are three differences between experimental/control groups, out of 33 listed characteristics that could have been different. There is approximately a 23% chance (he calculates) that you could get these differences by chance. He accuses me of failing to do a formal Carlisle test - the usual test you would use to determine whether weird differences between randomized groups are because of fraud - instead eyeballing it and getting it wrong. Here I do want to defend myself: I am not accusing Ghauri et al of fraud. In fact, this would be nonsensical: they admit they are assigning patients nonrandomly. Carlisle tests are usually done to show that something about group assignment is impossible (and therefore fraudulent) in a fair random assignment. But these people aren’t claiming to have done a fair random assignment, so I’m not sure what a Carlisle test would prove. My argument is more like: this is nonrandom, therefore we should expect it to be unfair. It is unnecessary, but helpful, to note an actual apparent unfairness - there’s some evidence they gave the ivermectin to less severe patients (as measured by corticosteroid use). Therefore, we can’t necessarily trust this to be a fair trial (which it was never really claiming to be). In the end I kept Ghauri as an okay study, although GMK didn’t so it ended out trashed in the final analysis anyway. I think my thinking was that I never claimed to be only looking at RCTs, so this non-RCT whose between-group-differences confirmed that it was indeed a non-RCT with all the risk of bias that entails, didn’t necessarily need to be ruled out. Still, I don’t think I was wrong to mention this possibility, and I think Alexandros was wrong to suggest that I needed to do extra tests for this to be fair. Borody et al (still disagree with Alexandros) I described this as: Our last paper! …is it a paper? I can’t find it published anywhere. It mostly seems to be on news sites. Doesn’t look peer-reviewed. And it starts with “Note that views expressed in this opinion article are the writer’s personal views”. Whatever. 600 Australians were treated with ivermectin, doxycycline, and zinc. The article compares this to an “equivalent control group” made of “contemporary infected subjects in Australia obtained from published Covid Tracking Data”; this is not how you control group, @#!% you. Then it gets excited about the fact that most patients had better symptoms at the end of the ten-day study period than the beginning (untreated COVID resolves in about ten days). Why are these people wasting my time with this? Let’s move on. Alexandros lists his full concerns here. My summary: Scott is being incredibly disrespectful to the authors, who are in fact a legendary gastroenterologist who invented life-saving h. pylori therapy and a brilliant immunologist who invented a well-regarded bronchitis vaccine (in particular, in describing their control group, I said “this is not how you control group, @#!% you”.
risperidone

risperidone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "a medium dose of the antipsychotic risperidone is 2 mg/day". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
risperidone
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
On the other hand, the worst Chinese/Ayurvedic/marine supplement had 2000 mcg of arsenic in it. That’s 2 mg. For context, a medium dose of the antipsychotic risperidone is 2 mg/day. So these supplements contained as much arsenic as a risperidone pill does of risperidone. How do you end up with that much arsenic in a pill? I think some traditional Chinese medicines might, uh, be arsenic. In fact, the study mentions that one traditional Chinese remedy is cinnabar, ie mercury sulfide. Isn’t this how Qin Shi Huang Di died?
rituximab

rituximab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 24, 2024 and April 24, 2024. The archive places it in contexts such as "anti-lymphoma drug rituximab". It most often appears alongside 2008 America, @agoodmanbacon, Baicker.

Reference entry
rituximab
Mention count
1
Issue count
1
First seen
April 24, 2024
Last seen
April 24, 2024
April 24, 2024 · Original source
(source) People with cancer are more likely to survive than fifty years ago. This is after you’ve already gotten the cancer, so it’s hard to see how nutrition, sanitation, etc could explain this. Some of these changes (especially prostate) are a result of earlier diagnosis. But others reflect genuinely better treatment. For example, studies have shown great results from the anti-leukemia drug imatinib and the anti-lymphoma drug rituximab. In Robin’s model, these extraordinary studies would have to be bias or chance, and totally coincidentally at the same time somehow better nutrition made leukemia patients (but not uterine cancer patients) twice as likely to survive. Might this be because people are getting cancer younger (and therefore are better able to deal with it?) I can’t find great data on this; there’s increasing cancer among younger people, but (since people are living longer) we should also expect increasing cancer among older people (since there are more older people). Rather than try to figure out how to balance these effects, here’s a graph showing similar survival improvements among childhood cancers in particular, where we wouldn’t expect this to be a problem: (source) Likewise, here is post-heart attack 30-day mortality rate over time: Source here. The odds of death within 30 days of a heart attack have fallen from 20% in 1995 to 12.4% in 2015 (source). This is also no mystery; the improvement comes from increased use of basic drugs like ACEIs, aspirin, and beta-blockers, plus more advanced interventions like thrombolytics and angioplasties, plus logistical improvements like more heart attack patients being placed on specialized cardiac wards. Again, can we dismiss this because maybe heart attack victims are younger? The study this particular graph comes from says their patients were on average 2.7 years older at the end than the beginning, so here age effects seem to point in the opposite direction. Here’s a graph showing the same decline if you break it up by under- and over-65s, though I wish I could find something with smaller bins. Same data for stroke: Source here. Note that these are age-adjusted data! In 2000, a stroke victim is only half as likely to die in the first two years after their illness as they were in 1980. Here we don’t have to worry about age effects at all; the graph is already adjusted for age. You can see similar survival rate increases for other conditions like congestive heart failure (5-year survival rate went from 29% to 60% since 1970), multiple sclerosis (standardized mortality rate went from 3.1 to 0.7 since 1950), type 1 diabetes (survival rate at 50 from about 40% to 80% since 1950) and nearly any other condition you look up. I’m harping on this because it’s in some sense the central example of medicine: you get some deadly disease like cancer, and you want to know if doctors can help you survive or not. All the evidence suggests medicine has gotten much better at this in the past fifty years. Robin’s going to have a lot of hard-to-interpret studies about what happens to your cholesterol score or whatever after you change insurance, and we’ll pick these apart, but to me this seems like a much less central example of “does medicine work?” than the fact that we’re curing cancer and increasing heart attack survival rates. III. RAND Health Insurance Experiment This is considered the canonical study on the effect of health insurance. In the 1970s, RAND gave thousands of people one of five types of insurance, ranging from very bad (barely any coverage until a family reached a deductible of $1000, ie $5000 in today’s dollars) to very good (all care was free). Then they waited eight years. Then they checked whether the people on the good insurance ended up any healthier than the people on the bad insurance. The paper I found measured five questionnaire-based outcomes plus five objective physiological measures, for a total of ten outcomes (Robin says he has a book where they discuss 23 to 30 outcomes, but I don’t have that book, so I’m sticking with the paper). The ten in the paper I read were: Physical functioning questionnaire
Roadster

Roadster is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "Even after the Roadster, people said it was impossible Tesla could produce the Model S". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Roadster
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
When SpaceX was on its last few hundred thousand dollars, and the Falcon 1 kept blowing up, and no private company had ever launched a rocket to space before, and they only had a few weeks to make Falcon 1 fly and restore investor confidence before the company went bankrupt - Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9. The same thing happened with the Tesla Roadster and the Model S.
When SpaceX was on its last few hundred thousand dollars, and the Falcon 1 kept blowing up, and no private company had ever launched a rocket to space before, and they only had a few weeks to make Falcon 1 fly and restore investor confidence before the company went bankrupt - Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9. The same thing happened with the Tesla Roadster and the Model S. In every other way, no, he’s not a 4D chessmaster. His mistakes are real mistakes. He’s not secretive about his plans; more often he says them openly and nobody believes him. And many of his biggest victories came to him by luck, or at least by putting himself in a position where opportunity could strike.
Even after the Roadster, people said it was impossible Tesla could produce the Model S. Even after Falcon 1, people said it was impossible they could get reusable rockets. This is one of those cases where people comically refuse to update, again and again.
Roam

Roam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Think Airtable+Vensim+Roam+Kumu". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Roam
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#6: System Dynamics Simulator I'm Oleksandr Nikitin, and I want to build a system dynamics simulator. Enable independent researchers to simulate, forecast, and visualize metabolic pathways, epidemic spread, mass transit, ecology, macroeconomics, etc. Show, don't tell. Without code. Think Airtable+Vensim+Roam+Kumu, integrated and working offline. Why offline? Why simulate? Why a new tool? Complex systems must be simulated. You miss emergent phenomena if you analyze parts separately or simplify the details. Offline sets you free from distractions and groupthink. Free to make your own breakthroughs. Take your references, notes and data with you, dive deep, then return with the verified, reproducible, interactive model. Research can take years. Tools should outlast devices and app stores. And it must be fast. Isn’t it insane for a productivity tool to make you wait? I spent years on prototypes and algorithms, tested in companies since 2013, and now I want to put these experiments together. Not as a startup. As a tool accessible to everyone. The plan: create a community of curious inquisitive makers, empower them with a small fast and robust core app, iterate and grow together, augment the human intelligence even more, and understand the world. I seek funding to focus on this project full-time, for two years. To launch and to guide people to the finished research. Sounds inspiring? Worth the money? Want more details? Ping me at oleksandr@tvori.info. Also see https://cortex.substack.com/
Robin Hood

Robin Hood is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2022 and December 20, 2022. The archive places it in contexts such as ""...trade stocks on Robin Hood, or (in 20 states) place online sports bets on sites like DraftKings."". It most often appears alongside 7-11, AGI, AMC.

Reference entry
Robin Hood
Mention count
1
Issue count
1
First seen
December 20, 2022
Last seen
December 20, 2022
December 20, 2022 · Original source
After the event happens, use the outcome to update everyone’s reputation and refine the algorithm. Superforecasting uses some of the same ideas as prediction markets - probabilistic forecasts, incentives to get the right answer, aggregation methods that favor people with good track records. In studies comparing superforecasting tournaments to small prediction markets, the superforecasting tournaments have done equally well or even slightly better. My goal with this FAQ is not to claim that prediction markets are always better than superforecasting. I think of both as part of the same revolution in forecasting technology, and would be happy with policy-makers or other important people using either. Still, I do think that each has situations where they might be a better fit than the other. Superforecasting tournaments shine on questions so far in the future that financial incentives start to lose force (for example, people are unlikely to place bets on questions about 2100, when most of them will be dead anyway). They’re also good in situations where you can’t get a big prediction market together - superforecasting scales down more gracefully, since you can identify individuals as superforecasters and consult them even in situations where you can’t get a full tournament together. Prediction markets shine in avoiding advanced manipulation attempts, in providing a single canonical answer when someone might worry that any given tournament was biased, and in aggregating the results of superforecaster tournaments with each other and with other sources. Remember that a superforecasting tournament can be considered an “expert”, like Nate Silver. So by the argument in Part 2, we should expect that a big prediction market won’t consistently be worse than any given superforecasting tournament, as long as the tournament’s answers are public knowledge. If there were ever a superforecasting tournament that consistently outperformed prediction markets, that would be a simple mispricing, people would correct it, and the market would eventually agree with the tournament. 4.5: Aren’t prediction markets gambling? Isn’t gambling bad and addictive? Yes, sort of. But most countries allow forms of gambling that aren’t too addictive and have some social value. For example, investing in stocks, or investing in commodities futures. I think prediction markets are more like this than like traditional gambling in casinos. People who want to gamble can already buy cryptocurrencies, or trade stocks on Robin Hood, or (in 20 states) place online sports bets on sites like DraftKings. All these things seem more addictive than, and have less social utility than, prediction markets. I don’t think promoting or legalizing prediction markets is going to make the gambling situation much worse than it is already - so given how useful I think they are, I think they would be net positive. People who are more concerned about the gambling aspect might want to stick to play money prediction markets, which wouldn’t have this problem. 4.6: Where does the money in prediction markets come from? That is, if "you get a dollar when the Democrats win”, who provides the dollar? In the abstract, prediction markets pair up people who want to bet on different sides of a proposition. For example, if a market says that there’s a 75% chance that the Democrats win, then they pair up someone willing to buy a share in “The Democrats win” for $0.75 with someone willing to buy a share in “The Democrats lose” for $0.25, for a total of $1 spent on these two shares. Then, when the Democrats either win or lose, the person with the correct share gets the $1. In practice it’s annoying to have to wait for someone to take the opposite side of the trade, so some people (or bots!) play “market maker” and are willing to take your bet on the assumption that someone else will come along soon to take the other side. But it’s usually safe to abstract this step away and just imagine people betting with each other, using the market as an intermediary. 4.6.1: Then why should anyone play prediction markets, when on average they’ll only break even? It seems like this is a worse deal than stocks, which tend to go up over time. Every dollar someone wins on a prediction market corresponds to someone else’s loss; in expectation; across all participants, the average gain is 0. But the stock market tends to go up over time, as businesses expand to new areas and invent new products; across all participants, the average gain is about 4% per year. So why ever invest in prediction markets instead of stocks? Whatever the theoretical answer to this question, lots of people do invest in prediction markets instead of stocks sometimes; several existing prediction markets have questions with hundreds of thousands of dollars in trading volume. You would have to ask those people why they do it. Maybe it’s because it’s fun. Or maybe it’s because they think (rightly or wrongly) that they’re above average and can make a profit. This is no different than other zero-sum games like sports betting, which attracts billions of dollars each year. The futures and commodities markets are also zero-sum, but attract billions of dollars by giving companies an opportunity to hedge risk. For example, a nickel mine might get rich if the price of nickel goes up, but go bankrupt if the price of nickel goes down. And they might prefer a predictable world where they get a small but guaranteed profit no matter what happens to nickel prices. So they bet some amount of money on commodity markets that the price of nickel will go down, and then their income is the sum of what they make from their nickel mining and from their bets - which, if they handled their hedging correctly, should be a small but guaranteed profit. Prediction markets would allow hedging of other types of risk - for example, import-export businesses might want to hedge against the risk that a protectionist politician gets elected, or tourism companies might want to hedge against a pandemic that closes international borders. These people would inject enough money into the market to subsidize sophisticated speculators. Finally, I envision that someday people who want to know the answer to specific questions can subsidize prediction markets on them. For example, the Democratic Party might subsidize a conditional market (see 5.1) about which Democratic primary candidate is most likely to win the general election. Their money would go to giving the average investor a 4% (or some other number) rate of return - although of course winners would gain more than that and losers would still lose on net. I think this is the most likely way for prediction markets to become very big. 4.6.1.1: If people use prediction markets to hedge risk, won’t that distort them? That is, suppose that an import-export business spends millions of dollars betting that Trump will win in order to hedge against his protectionist policies. Since their bets aren’t based on the real chance of Trump winning, won’t that distort the market? No. Suppose that everyone knows Trump has a 50-50 chance of winning. And suppose the import-export business, in the process of hedging risk, bids it up to 90-10. Since you know Trump has a 50-50 chance of winning, you can get rich quick by bidding it back down to 50-50. From your point of view, the import-export business is (in expectation) giving you free money. But they’re still happy to do it, because they’re hedging their risk successfully. 4.7: Aren’t a lot of the questions we care about inherently subjective or hard to measure? This is a frequent problem for prediction markets. For example, we might want to know something like “will we get human-level AI before 2050?” But how do we define “human-level AI”? If there’s an AI that’s much better than humans at most tasks, but much worse at a few, is that “human-level”? If there’s an AI that seems human-level in demos, but the team that makes it won’t let it be independently tested, should that count? If it works through some kind of Frankenstein chip that combines vat-grown brain tissue with computing machinery, is that still an “AI”? Prediction markets have found a few ways around this problem. First, many groups (for example, Metaculus) try to define their resolution criteria very carefully. A typical Metaculus question on AI sounds like this: We will thus define "an AI system" as a single unified software system that can satisfy the following criteria, all completable by at least some humans. Able to reliably pass a 2-hour, adversarial Turing test during which the participants can send text, images, and audio files (as is done in ordinary text messaging applications) during the course of their conversation. An 'adversarial' Turing test is one in which the human judges are instructed to ask interesting and difficult questions, designed to advantage human participants, and to successfully unmask the computer as an impostor. A single demonstration of an AI passing such a Turing test, or one that is sufficiently similar, will be sufficient for this condition, so long as the test is well-designed to the estimation of Metaculus Admins.
Robinhood

Robinhood is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 13, 2026 and January 13, 2026. The archive places it in contexts such as "published to a real-time dashboard integrated as part of the Robinhood UI". It most often appears alongside Adeline, Aella Simposium, Altman.

Reference entry
Robinhood
Mention count
1
Issue count
1
First seen
January 13, 2026
Last seen
January 13, 2026
January 13, 2026 · Original source
“When a company is doing its FDA studies,” says Bob, “we pay the study participants to use wearables that report real-time temperature, heart rate, respiratory rate, blood pressure, heart rate variability, galvanic skin response, penile tumescence. Then they get anonymized and published to a real-time dashboard integrated as part of the Robinhood UI. So you can see a red line representing how study participant #48 had a coughing fit ten seconds ago, and immediately short the experimental cancer drug he’s taking.”
Roboflow

Roboflow is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 29, 2025 and August 29, 2025. The archive places it in contexts such as "I'll be wearing a purple "Roboflow" hat". It most often appears alongside "Beer Capital" pub, 100 Black Birch Trail, 11841 Wagner Street, Culver City.

Reference entry
Roboflow
Mention count
1
Issue count
1
First seen
August 29, 2025
Last seen
August 29, 2025
August 29, 2025 · Original source
Contact: Linas Contact Info: linas[dot]ko[at]pm[dot]me Time: Sunday, September 21st, 4:00 PM Location: I'll be wearing a purple "Roboflow" hat. Coordinates: https://plus.codes/9G67M7QC+R7 Group Link: https://discord.gg/jqxuBM [remove this bit] eHaw Additional Notes: The latest event details can be found in: https://discord.gg/y9KNuzRb?event=1412003421908766800
Rocket Math

Rocket Math is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 27, 2025 and June 27, 2025. The archive places it in contexts such as ""Fast Math" (doing simple math ... mostly on 'Rocket Math')". It most often appears alongside 10,000 hour rule, 2 Hour Learning, Inc, 2-hour Learning.

Reference entry
Rocket Math
Mention count
1
Issue count
1
First seen
June 27, 2025
Last seen
June 27, 2025
June 27, 2025 · Original source
“Fast Math” (doing simple math they already know how to do faster and more accurately; mostly on “Rocket Math” or “FastMath Pro”)
Rolex

Rolex is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 22, 2022 and July 22, 2022. The archive places it in contexts such as "How does everybody know that they should want a Rolex". It most often appears alongside 2020 election, 2022 book review contest, 2122.

Reference entry
Rolex
Mention count
1
Issue count
1
First seen
July 22, 2022
Last seen
July 22, 2022
July 22, 2022 · Original source
Cover of The Society of the Spectacle He never outright explains why he thought photos and film were more pernicious than newspapers or radio, but I imagine the advertising industry played a major role. We’ve grown accustomed to GoDaddy ads and ALL CAPS YouTube titles, but Mad Men shenanigans were a worrisome development at the time. It must’ve been highly alarming to see such brazen manipulation of the public. Whatever the reasoning, we now arrive at one definition of the spectacle: "The spectacle is capital accumulated to the point that it becomes images." Also: “The spectacle is not a collection of images; it is a social relation between people that is mediated by images.” Well, that’s about as clear as Flint water. Here’s something meatier: "In all of its particular manifestations — news, propaganda, advertising, entertainment — the spectacle represents the dominant model of life." If you’re familiar with Girard, that is a huge statement. [3] Girardian mimetic desire is triangular; there is you (the desirer), the object (of desire), and the model (another person who also desires the object). Most of our desires are rooted in imitation. Nobody has to tell you to want steak or sex, but almost everything else is learned. How does everybody know that they should want a Rolex or a Rolls Royce? There’s no genetic imperative for luxury goods. You acquire those tastes from the people around you. Or you used to, at least. Before the spectacle, your models, mentors, and rivals were real people you knew in real life. Now we have an acronym for that - IRL - because reality is everywhere in retreat. This is not a small thing. What we desire is at the core of who we are. What do you want out of life? What kind of person do you want to be? For the entirety of human history, those questions found answers close at hand. Your local community was your world, for better and worse. Now we are global citizens with global perspectives, and it’s difficult to overstate how much that changes what it means to be human. Imprisoned in a flattened universe bounded by the screen of the spectacle that has enthralled him, the spectator knows no one but the fictitious speakers who subject him to a one-way monologue about their commodities and the politics of their commodities. The spectacle as a whole serves as his looking glass. What he sees there are dramatizations of illusory escapes from a universal autism. The spectacle’s estrangement from the acting subject is expressed by the fact that the individual’s gestures are no longer his own; they are the gestures of someone else who represents them to him. Now our role models are media creations. Some are literal fictional characters (James Bond); others are nominally real people (Kylie Jenner). But both are merely representations - images usurping an essential formative role. ‘William Shatner’ and ‘Robert Downey, Jr.’ are only marginally more real than Captain Kirk and Tony Stark, yet they occupy way more headspace than people that live down the street. Most people can name more celebrities, in more detail, than people they’ve known in person. I know the names of Will Smith’s kids - I don’t even know if my best friends from high school have any. This is an issue of The Map and The Territory. Pre-modern Maps were narrow but deep. You might have had only a vague notion of ‘Africa’ or ‘The Pope’, but you knew every square inch of the town you lived in. Spectacular Maps are broad but shallow, and they are drawn for us by spectacular hands. The average person ‘knows’ way more about Africa now, but how well does that knowledge reflect the facts on the ground? Meanwhile, firsthand reality has been reduced to the narrow slices connecting house to car to work, with precious few exceptions. The Society Of The Spectacle is one long lament for this loss of The Real, although Debord doesn’t state it as such. Borrowing again from The Uruk Machine, this sense of loss tracks with the gradual displacement of metis [4] by episteme [5],[6]. III. Everything New Is Old Again Debord has a lot to say about the ‘falsification of the world’: The first stage of the economy’s domination of social life brought about an evident degradation of being into having — human fulfillment was no longer equated with what one was, but with what one possessed. The present stage, in which social life has become completely dominated by the accumulated productions of the economy, is bringing about a general shift from having to appearing — all ‘having’ must now derive its immediate prestige and its ultimate purpose from appearances. As he might have put it - we have graduated from conspicuous consumption to consuming conspicuousness. Spectacular technology has not dispersed the religious mists into which human beings had projected their own alienated powers, it has merely brought those mists down to earth, to the point that even the most mundane aspects of life have become impenetrable and unbreathable. In the spectacle, a part of the world presents itself to the world and is superior to it. The spectacle is simply the common language of this separation. Spectators are linked solely by their one-way relationship to the very center that keeps them isolated from each other. The spectacle thus reunites the separated, but it reunites them only in their separateness. These themes are familiar to us by now. It’s not exactly news that people are getting more isolated and untethered by the year. What is striking to me is not what he is saying, but when he is saying it. Anybody with sense has spent time thinking about how to manage the challenges of modern life. We talk about digital minimalism and social media fasts. Turn off your phone. Get outside and touch grass. Go see people in meatspace. Be present. All great advice. But what are we envisioning, when we imagine a healthy connection to The Real? For most of us, we are picturing life as it was lived… right around the time Debord was saying that everything is phony and toxic. What does the average person think of as the peak of journalistic integrity in America? Probably Vietnam and Watergate - right after this was written. When we mock Millennials and Zoomers, what standard are we measuring them by? The Greatest Generation, who were running the show by the late sixties. In terms of self-reliance and resilience, the average adult in 1967 would be a massive outlier in 2022. Yet here is Debord, saying in no uncertain terms that this American ideal was fraudulent and devoid of meaning. What have we lost? Every era has its cynics, doomsayers, Luddites, and misanthropes. Maybe Debord was just a Boomer’s Boomer, railing against progress and the passage of time. But I don’t think so. We’ve all felt the shockwaves of the Internet explosion. Life is different now. It takes an act of will to put down your phone so you can focus on the TV. Low battery is an emergency. Losing signal is bereavement. Navigating without GPS is an anxiety attack. Do you remember what it was like, not so long ago? How exciting it was to play videogames with someone a thousand miles away? How cool it was the first time you streamed a movie on an airplane? That sense of possibility and promise, like all the world was in the palm of your hand? How quickly things change. For maybe the first time in history, most people are apprehensive about the relentless march of technology. While we’ve always been afraid of advances in weaponry, it’s starting to feel like everything is being weaponized. Who truly believes the metaverse will be a positive step for humanity? Who now is excited at the prospect of gene editing, AI, or transhumanism? There appears to be a growing sentiment along the lines of ‘MGTOW for modernism’. We hope for the best, but 2122 is shaping up to be some unholy amalgam of Gattaca, The Matrix, and Minority Report. Sometimes it seems like the world we grew up in is categorically distinct from the world we inhabit. But I’m sure Debord would argue that we are merely experiencing an intensification of a process that has been in motion longer than any of us have been alive. Pre-spectacular society has already passed beyond living memory. Soon we will hit another inflection point - where no one alive even knew someone who lived before the spectacle. All of human history is now before and after; it will soon become literally impossible to understand the inner life and daily reality of pre-modern man - if it’s not already. As an example: how much of your daily environment, as a percentage, do you truly understand? Look around the room and reflect on how “even the most mundane aspects of life have become impenetrable and unbreathable.” Your kitchen and your medicine cabinet are filled with mystical objects. Hell, just look at what’s on your person. The phone in your hand, the cash in your wallet, the clothes on your back, the food in your belly - how many lifetimes would it take to truly grok the building blocks of everyday existence? Compare that to, say, a homesteader. It really hasn’t been that long since people lived in a comprehensible universe. Our collective knowledge of the universe has deepened tremendously, but theoretical physics is only less slightly hermetical than the occult beliefs it replaced. It is notionally true that anyone could go get a Ph.D. and verify our working model of the cosmos. But in practice, the science is received wisdom, taken on faith. Our belief in the God Particle is functionally indistinguishable from the belief in God of ages past. It’s worth noting that our current theories will surely be supplanted in a century or three. They are placeholders for better, truer ideas. And so our greater grasp of the wider world has less value than we think, while our day-to-day grows ever more opaque. Is it any wonder epistemic learned helplessness is a thing? IV. With Typical Extravagance Debord was also ahead of the curve on commoditization: This constant expansion of economic power in the form of commodities transformed human labor itself into a commodity, into wage labor, and ultimately produced a level of abundance sufficient to solve the initial problem of survival — but only in such a way that the same problem is continually being regenerated at a higher level. Economic growth has liberated societies from the natural pressures that forced them into an immediate struggle for survival; but they have not yet been liberated from their liberator. Once his workday is over, the worker is suddenly redeemed from the total contempt toward him that is so clearly implied by every aspect of the organization and surveillance of production, and finds himself seemingly treated like a grownup, with a great show of politeness, in his new role as a consumer. Debord correctly perceived the totalitarian nature of spectacular capitalism. Your time, your attention, your opinions - all are bought and sold, and can be influenced to better facilitate such transactions. He would have been totally unsurprised by the rise of Big Data and the corporate surveillance (e.g. Alexa, your phone) that accompanies it. Every piece of your life is a commodity. Every moment that you are not producing or consuming is a missed opportunity. Never fear - someone, somewhere is going to find a way to solve that ‘need’. Nothing is spared. Even opposition is assimilated: Complacent acceptance of the status quo may also coexist with purely spectacular rebelliousness — dissatisfaction itself becomes a commodity as soon as the economy of abundance develops the capacity to process that particular raw material. Once again, Debord is shockingly prescient in noting that the conflicts of our time are largely distractions from bigger systemic issues: Fallacious archaic oppositions are revived — regionalisms and racisms which serve to endow mundane rankings in the hierarchies of consumption with a magical ontological superiority — and pseudoplayful enthusiasms are aroused by an endless succession of ludicrous competitions, from sports to elections. Genuine grassroots movements (Occupy, the Tea Party, BLM, Canadian truckers) almost always fizzle out without accomplishing anything of substance. They will either be ignored, crushed, or co-opted. Any remnants that endure will be reduced to figureheads that offer ‘representation’ for a point of view without actually producing any change. (‘The Squad’, Rand Paul, etc…) If the extremes of either side gain enough momentum to pose a threat, they will face a united front from the establishment wings of both parties (Bernie, Trump). It’s fashionable at the moment to blame the Woke Left for the politicization of everything, but we’ve all been around long enough to know better. It’s the same shit, different decade. During the Bush years, it was the left who opposed unending wars, government overreach, and media gaslighting. Today those positions are often considered right wing, but only because the pendulum of power has swung in the other direction. Moloch pursues its own goals, wearing whatever ideological guise it deems most effective. From Debord’s perspective, everything is becoming politicized because everything is getting monetized. In the integrated spectacle, the primary concerns of the State are economic, so the personal turning political is simply a downstream effect of the growth of capitalism. V. A Short History of Time It would do Debord a disservice to reduce his work to ammunition in our present disputes. There are two whole chapters in the book devoted to time as a historical development. It’s not something we think about much, but time and history had to be invented. Before the beginning, humanity lived in what Debord calls cyclical time. Countless generations came and went, because nobody was counting. Survival was the name of the game; to be or not to be was the only question. Eventually we formed early societies, which brought into being a ruling class that had the freedom to take actions above and beyond the daily grind: The owners of this historical surplus value are the only ones in a position to know and enjoy real events. Separated from the collective organization of time associated with the repetitive production at the base of social life, this historical time flows independently above its own static community. This is the time of adventure and war, the time in which the masters of cyclical society pursue their personal histories; it is also the time that emerges in the clashes with foreign communities that disrupt the unchanging social order. History thus arises as something alien to people, as something they never sought and from which they had thought themselves protected. The murkiness of pre-civilization was shaped into coherence by these rulers, who used their unique agency to literally make history: The succession of generations within a natural, purely cyclical time begins to be replaced by a linear succession of powers and events. This irreversible time is the time of those who rule, and the dynasty is its first unit of measurement. With writing there appears a consciousness that is no longer carried and transmitted directly among the living — an impersonal memory, the memory of the administration of society. ‘Writings are the thoughts of the state; archives are its memory’ (Novalis). The owners of history have given time a direction, a direction which is also a meaning. But this history develops and perishes separately, leaving the underlying society unchanged, because it remains separated from the common reality. Over time, these narratives gathered a religious dimension. This helped legitimize the rule of regimes, but it also changed the way ordinary people saw themselves in the world. Although still living in cyclical time, they gained purpose through a spiritual journey culminating in Heaven. The clashes of the Mediterranean peoples and the rise and fall of the Roman state gave rise instead to semihistorical religions, which became a new armor for separate power and basic components of a new consciousness of time. The Middle Ages, an incomplete mythical world whose consummation lay outside itself, is the period when cyclical time, though still governing the major part of production, really begins to be undermined by history. An element of irreversible time is recognized in the successive stages of each individual’s life. Life is seen as a one-way journey through a world whose meaning lies elsewhere: the pilgrim is the person who leaves cyclical time behind and actually becomes the traveler that everyone else is symbolically. The Renaissance created a profound break with this mythic raison d'être and reoriented man towards the accumulation of knowledge as a species: The Renaissance was a joyous break with eternity. Though seeking its heritage and legitimacy in the ancient world, it represented a new form of historical life. Its irreversible time was that of a never-ending accumulation of knowledge… This transformation of our relationship with history and progress was accompanied by the rise of the bourgeoisie: The bourgeoisie is associated with a labor time that has finally been freed from cyclical time. With the bourgeoisie, work becomes work that transforms historical conditions. The bourgeoisie is the first ruling class for which work is a value. The victory of the bourgeoisie is the victory of a profoundly historical time, because it is the time corresponding to an economic production that continuously transforms society from top to bottom. So long as agrarian production remains the predominant form of labor, the cyclical time that remains at the base of society reinforces the joint forces of tradition, which tend to hold back any historical movement. But the irreversible time of the bourgeois economy eradicates those vestiges throughout the world. History, which until then had seemed to involve only the actions of individual members of the ruling class, and which had thus been recorded as a mere chronology of events, is now understood as a general movement — a relentless movement that crushes any individuals in its path. Irreversible time initially appeared at the societal level as a narrative of events. The bourgeoisie brought irreversible time to the masses. Progress became something that we personally experience in the form of rapid technological innovation. It is hard to miss the motion of history when you go from horses to space travel in a single lifetime. History thus became as much about things as events. Eli Whitney and Thomas Edison took their places alongside generals and heads of state in our narrative of who we are and where we’re going. Our notion of progress became dominated by the economic prejudice. We talk about raising the standard of living and lifting people out of poverty - laudable goals, to be sure - but we deliver them from physical privation into deprivation of a different kind. One way that deprivation manifests is in our current conception of time: Pseudocyclical time is associated with the consumption of modern economic survival — the augmented survival in which everyday experience is cut off from decisionmaking and subjected no longer to the natural order, but to the pseudo-nature created by alienated labor. It is thus quite natural that it echoes the old cyclical rhythm that governed survival in preindustrial societies, incorporating the natural vestiges of cyclical time while generating new variants: day and night, work and weekend, periodic vacations." As capitalism commoditized time itself, we recreated cyclical time with the standard work week. But this artificial substitute has been about as successful as vegan chicken nuggets. It’s not the same, and it never will be. The workday used to be determined by the work, but now the work is determined by the workday. And everyone has to work, not because we need what they produce, but because we need them to spend - else the whole thing comes crashing down. Irreversible time keeps marching on, giving us new widgets and new wonders, but the continual churn of innovation masks the stifling sameness of spectacular progress. We know something is missing, but we lack the capacity to understand or express the problem. This individual experience of a disconnected everyday life remains without language, without concepts, and without critical access to its own past, which has nowhere been recorded. Uncommunicated, misunderstood and forgotten, it is smothered by the spectacle's false memory of the unmemorable. VI. The Coming Revolution Debord spends a good chunk of words describing how the spectacle has affected art [7] and physical space, but you can guess the gist by now. Everything’s fake, everything’s worse, everything’s changing but also the same. The last topic of the book worth discussing is the imminent socialist revolution. Debord walks us through the various ways that Marxism has been done wrong, then attempts to offer an alternative. He goes into a fair amount of detail, but it boils down to this: The anarchists properly rejected society in its entirety, but remained dogmatically attached to a 'one size fits all' mentality and failed to organize in an effective manner.
Rolls Royce

Rolls Royce is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 22, 2022 and July 22, 2022. The archive places it in contexts such as "How does everybody know that they should want a Rolex or a Rolls Royce?". It most often appears alongside 2020 election, 2022 book review contest, 2122.

Reference entry
Rolls Royce
Mention count
1
Issue count
1
First seen
July 22, 2022
Last seen
July 22, 2022
July 22, 2022 · Original source
Cover of The Society of the Spectacle He never outright explains why he thought photos and film were more pernicious than newspapers or radio, but I imagine the advertising industry played a major role. We’ve grown accustomed to GoDaddy ads and ALL CAPS YouTube titles, but Mad Men shenanigans were a worrisome development at the time. It must’ve been highly alarming to see such brazen manipulation of the public. Whatever the reasoning, we now arrive at one definition of the spectacle: "The spectacle is capital accumulated to the point that it becomes images." Also: “The spectacle is not a collection of images; it is a social relation between people that is mediated by images.” Well, that’s about as clear as Flint water. Here’s something meatier: "In all of its particular manifestations — news, propaganda, advertising, entertainment — the spectacle represents the dominant model of life." If you’re familiar with Girard, that is a huge statement. [3] Girardian mimetic desire is triangular; there is you (the desirer), the object (of desire), and the model (another person who also desires the object). Most of our desires are rooted in imitation. Nobody has to tell you to want steak or sex, but almost everything else is learned. How does everybody know that they should want a Rolex or a Rolls Royce? There’s no genetic imperative for luxury goods. You acquire those tastes from the people around you. Or you used to, at least. Before the spectacle, your models, mentors, and rivals were real people you knew in real life. Now we have an acronym for that - IRL - because reality is everywhere in retreat. This is not a small thing. What we desire is at the core of who we are. What do you want out of life? What kind of person do you want to be? For the entirety of human history, those questions found answers close at hand. Your local community was your world, for better and worse. Now we are global citizens with global perspectives, and it’s difficult to overstate how much that changes what it means to be human. Imprisoned in a flattened universe bounded by the screen of the spectacle that has enthralled him, the spectator knows no one but the fictitious speakers who subject him to a one-way monologue about their commodities and the politics of their commodities. The spectacle as a whole serves as his looking glass. What he sees there are dramatizations of illusory escapes from a universal autism. The spectacle’s estrangement from the acting subject is expressed by the fact that the individual’s gestures are no longer his own; they are the gestures of someone else who represents them to him. Now our role models are media creations. Some are literal fictional characters (James Bond); others are nominally real people (Kylie Jenner). But both are merely representations - images usurping an essential formative role. ‘William Shatner’ and ‘Robert Downey, Jr.’ are only marginally more real than Captain Kirk and Tony Stark, yet they occupy way more headspace than people that live down the street. Most people can name more celebrities, in more detail, than people they’ve known in person. I know the names of Will Smith’s kids - I don’t even know if my best friends from high school have any. This is an issue of The Map and The Territory. Pre-modern Maps were narrow but deep. You might have had only a vague notion of ‘Africa’ or ‘The Pope’, but you knew every square inch of the town you lived in. Spectacular Maps are broad but shallow, and they are drawn for us by spectacular hands. The average person ‘knows’ way more about Africa now, but how well does that knowledge reflect the facts on the ground? Meanwhile, firsthand reality has been reduced to the narrow slices connecting house to car to work, with precious few exceptions. The Society Of The Spectacle is one long lament for this loss of The Real, although Debord doesn’t state it as such. Borrowing again from The Uruk Machine, this sense of loss tracks with the gradual displacement of metis [4] by episteme [5],[6]. III. Everything New Is Old Again Debord has a lot to say about the ‘falsification of the world’: The first stage of the economy’s domination of social life brought about an evident degradation of being into having — human fulfillment was no longer equated with what one was, but with what one possessed. The present stage, in which social life has become completely dominated by the accumulated productions of the economy, is bringing about a general shift from having to appearing — all ‘having’ must now derive its immediate prestige and its ultimate purpose from appearances. As he might have put it - we have graduated from conspicuous consumption to consuming conspicuousness. Spectacular technology has not dispersed the religious mists into which human beings had projected their own alienated powers, it has merely brought those mists down to earth, to the point that even the most mundane aspects of life have become impenetrable and unbreathable. In the spectacle, a part of the world presents itself to the world and is superior to it. The spectacle is simply the common language of this separation. Spectators are linked solely by their one-way relationship to the very center that keeps them isolated from each other. The spectacle thus reunites the separated, but it reunites them only in their separateness. These themes are familiar to us by now. It’s not exactly news that people are getting more isolated and untethered by the year. What is striking to me is not what he is saying, but when he is saying it. Anybody with sense has spent time thinking about how to manage the challenges of modern life. We talk about digital minimalism and social media fasts. Turn off your phone. Get outside and touch grass. Go see people in meatspace. Be present. All great advice. But what are we envisioning, when we imagine a healthy connection to The Real? For most of us, we are picturing life as it was lived… right around the time Debord was saying that everything is phony and toxic. What does the average person think of as the peak of journalistic integrity in America? Probably Vietnam and Watergate - right after this was written. When we mock Millennials and Zoomers, what standard are we measuring them by? The Greatest Generation, who were running the show by the late sixties. In terms of self-reliance and resilience, the average adult in 1967 would be a massive outlier in 2022. Yet here is Debord, saying in no uncertain terms that this American ideal was fraudulent and devoid of meaning. What have we lost? Every era has its cynics, doomsayers, Luddites, and misanthropes. Maybe Debord was just a Boomer’s Boomer, railing against progress and the passage of time. But I don’t think so. We’ve all felt the shockwaves of the Internet explosion. Life is different now. It takes an act of will to put down your phone so you can focus on the TV. Low battery is an emergency. Losing signal is bereavement. Navigating without GPS is an anxiety attack. Do you remember what it was like, not so long ago? How exciting it was to play videogames with someone a thousand miles away? How cool it was the first time you streamed a movie on an airplane? That sense of possibility and promise, like all the world was in the palm of your hand? How quickly things change. For maybe the first time in history, most people are apprehensive about the relentless march of technology. While we’ve always been afraid of advances in weaponry, it’s starting to feel like everything is being weaponized. Who truly believes the metaverse will be a positive step for humanity? Who now is excited at the prospect of gene editing, AI, or transhumanism? There appears to be a growing sentiment along the lines of ‘MGTOW for modernism’. We hope for the best, but 2122 is shaping up to be some unholy amalgam of Gattaca, The Matrix, and Minority Report. Sometimes it seems like the world we grew up in is categorically distinct from the world we inhabit. But I’m sure Debord would argue that we are merely experiencing an intensification of a process that has been in motion longer than any of us have been alive. Pre-spectacular society has already passed beyond living memory. Soon we will hit another inflection point - where no one alive even knew someone who lived before the spectacle. All of human history is now before and after; it will soon become literally impossible to understand the inner life and daily reality of pre-modern man - if it’s not already. As an example: how much of your daily environment, as a percentage, do you truly understand? Look around the room and reflect on how “even the most mundane aspects of life have become impenetrable and unbreathable.” Your kitchen and your medicine cabinet are filled with mystical objects. Hell, just look at what’s on your person. The phone in your hand, the cash in your wallet, the clothes on your back, the food in your belly - how many lifetimes would it take to truly grok the building blocks of everyday existence? Compare that to, say, a homesteader. It really hasn’t been that long since people lived in a comprehensible universe. Our collective knowledge of the universe has deepened tremendously, but theoretical physics is only less slightly hermetical than the occult beliefs it replaced. It is notionally true that anyone could go get a Ph.D. and verify our working model of the cosmos. But in practice, the science is received wisdom, taken on faith. Our belief in the God Particle is functionally indistinguishable from the belief in God of ages past. It’s worth noting that our current theories will surely be supplanted in a century or three. They are placeholders for better, truer ideas. And so our greater grasp of the wider world has less value than we think, while our day-to-day grows ever more opaque. Is it any wonder epistemic learned helplessness is a thing? IV. With Typical Extravagance Debord was also ahead of the curve on commoditization: This constant expansion of economic power in the form of commodities transformed human labor itself into a commodity, into wage labor, and ultimately produced a level of abundance sufficient to solve the initial problem of survival — but only in such a way that the same problem is continually being regenerated at a higher level. Economic growth has liberated societies from the natural pressures that forced them into an immediate struggle for survival; but they have not yet been liberated from their liberator. Once his workday is over, the worker is suddenly redeemed from the total contempt toward him that is so clearly implied by every aspect of the organization and surveillance of production, and finds himself seemingly treated like a grownup, with a great show of politeness, in his new role as a consumer. Debord correctly perceived the totalitarian nature of spectacular capitalism. Your time, your attention, your opinions - all are bought and sold, and can be influenced to better facilitate such transactions. He would have been totally unsurprised by the rise of Big Data and the corporate surveillance (e.g. Alexa, your phone) that accompanies it. Every piece of your life is a commodity. Every moment that you are not producing or consuming is a missed opportunity. Never fear - someone, somewhere is going to find a way to solve that ‘need’. Nothing is spared. Even opposition is assimilated: Complacent acceptance of the status quo may also coexist with purely spectacular rebelliousness — dissatisfaction itself becomes a commodity as soon as the economy of abundance develops the capacity to process that particular raw material. Once again, Debord is shockingly prescient in noting that the conflicts of our time are largely distractions from bigger systemic issues: Fallacious archaic oppositions are revived — regionalisms and racisms which serve to endow mundane rankings in the hierarchies of consumption with a magical ontological superiority — and pseudoplayful enthusiasms are aroused by an endless succession of ludicrous competitions, from sports to elections. Genuine grassroots movements (Occupy, the Tea Party, BLM, Canadian truckers) almost always fizzle out without accomplishing anything of substance. They will either be ignored, crushed, or co-opted. Any remnants that endure will be reduced to figureheads that offer ‘representation’ for a point of view without actually producing any change. (‘The Squad’, Rand Paul, etc…) If the extremes of either side gain enough momentum to pose a threat, they will face a united front from the establishment wings of both parties (Bernie, Trump). It’s fashionable at the moment to blame the Woke Left for the politicization of everything, but we’ve all been around long enough to know better. It’s the same shit, different decade. During the Bush years, it was the left who opposed unending wars, government overreach, and media gaslighting. Today those positions are often considered right wing, but only because the pendulum of power has swung in the other direction. Moloch pursues its own goals, wearing whatever ideological guise it deems most effective. From Debord’s perspective, everything is becoming politicized because everything is getting monetized. In the integrated spectacle, the primary concerns of the State are economic, so the personal turning political is simply a downstream effect of the growth of capitalism. V. A Short History of Time It would do Debord a disservice to reduce his work to ammunition in our present disputes. There are two whole chapters in the book devoted to time as a historical development. It’s not something we think about much, but time and history had to be invented. Before the beginning, humanity lived in what Debord calls cyclical time. Countless generations came and went, because nobody was counting. Survival was the name of the game; to be or not to be was the only question. Eventually we formed early societies, which brought into being a ruling class that had the freedom to take actions above and beyond the daily grind: The owners of this historical surplus value are the only ones in a position to know and enjoy real events. Separated from the collective organization of time associated with the repetitive production at the base of social life, this historical time flows independently above its own static community. This is the time of adventure and war, the time in which the masters of cyclical society pursue their personal histories; it is also the time that emerges in the clashes with foreign communities that disrupt the unchanging social order. History thus arises as something alien to people, as something they never sought and from which they had thought themselves protected. The murkiness of pre-civilization was shaped into coherence by these rulers, who used their unique agency to literally make history: The succession of generations within a natural, purely cyclical time begins to be replaced by a linear succession of powers and events. This irreversible time is the time of those who rule, and the dynasty is its first unit of measurement. With writing there appears a consciousness that is no longer carried and transmitted directly among the living — an impersonal memory, the memory of the administration of society. ‘Writings are the thoughts of the state; archives are its memory’ (Novalis). The owners of history have given time a direction, a direction which is also a meaning. But this history develops and perishes separately, leaving the underlying society unchanged, because it remains separated from the common reality. Over time, these narratives gathered a religious dimension. This helped legitimize the rule of regimes, but it also changed the way ordinary people saw themselves in the world. Although still living in cyclical time, they gained purpose through a spiritual journey culminating in Heaven. The clashes of the Mediterranean peoples and the rise and fall of the Roman state gave rise instead to semihistorical religions, which became a new armor for separate power and basic components of a new consciousness of time. The Middle Ages, an incomplete mythical world whose consummation lay outside itself, is the period when cyclical time, though still governing the major part of production, really begins to be undermined by history. An element of irreversible time is recognized in the successive stages of each individual’s life. Life is seen as a one-way journey through a world whose meaning lies elsewhere: the pilgrim is the person who leaves cyclical time behind and actually becomes the traveler that everyone else is symbolically. The Renaissance created a profound break with this mythic raison d'être and reoriented man towards the accumulation of knowledge as a species: The Renaissance was a joyous break with eternity. Though seeking its heritage and legitimacy in the ancient world, it represented a new form of historical life. Its irreversible time was that of a never-ending accumulation of knowledge… This transformation of our relationship with history and progress was accompanied by the rise of the bourgeoisie: The bourgeoisie is associated with a labor time that has finally been freed from cyclical time. With the bourgeoisie, work becomes work that transforms historical conditions. The bourgeoisie is the first ruling class for which work is a value. The victory of the bourgeoisie is the victory of a profoundly historical time, because it is the time corresponding to an economic production that continuously transforms society from top to bottom. So long as agrarian production remains the predominant form of labor, the cyclical time that remains at the base of society reinforces the joint forces of tradition, which tend to hold back any historical movement. But the irreversible time of the bourgeois economy eradicates those vestiges throughout the world. History, which until then had seemed to involve only the actions of individual members of the ruling class, and which had thus been recorded as a mere chronology of events, is now understood as a general movement — a relentless movement that crushes any individuals in its path. Irreversible time initially appeared at the societal level as a narrative of events. The bourgeoisie brought irreversible time to the masses. Progress became something that we personally experience in the form of rapid technological innovation. It is hard to miss the motion of history when you go from horses to space travel in a single lifetime. History thus became as much about things as events. Eli Whitney and Thomas Edison took their places alongside generals and heads of state in our narrative of who we are and where we’re going. Our notion of progress became dominated by the economic prejudice. We talk about raising the standard of living and lifting people out of poverty - laudable goals, to be sure - but we deliver them from physical privation into deprivation of a different kind. One way that deprivation manifests is in our current conception of time: Pseudocyclical time is associated with the consumption of modern economic survival — the augmented survival in which everyday experience is cut off from decisionmaking and subjected no longer to the natural order, but to the pseudo-nature created by alienated labor. It is thus quite natural that it echoes the old cyclical rhythm that governed survival in preindustrial societies, incorporating the natural vestiges of cyclical time while generating new variants: day and night, work and weekend, periodic vacations." As capitalism commoditized time itself, we recreated cyclical time with the standard work week. But this artificial substitute has been about as successful as vegan chicken nuggets. It’s not the same, and it never will be. The workday used to be determined by the work, but now the work is determined by the workday. And everyone has to work, not because we need what they produce, but because we need them to spend - else the whole thing comes crashing down. Irreversible time keeps marching on, giving us new widgets and new wonders, but the continual churn of innovation masks the stifling sameness of spectacular progress. We know something is missing, but we lack the capacity to understand or express the problem. This individual experience of a disconnected everyday life remains without language, without concepts, and without critical access to its own past, which has nowhere been recorded. Uncommunicated, misunderstood and forgotten, it is smothered by the spectacle's false memory of the unmemorable. VI. The Coming Revolution Debord spends a good chunk of words describing how the spectacle has affected art [7] and physical space, but you can guess the gist by now. Everything’s fake, everything’s worse, everything’s changing but also the same. The last topic of the book worth discussing is the imminent socialist revolution. Debord walks us through the various ways that Marxism has been done wrong, then attempts to offer an alternative. He goes into a fair amount of detail, but it boils down to this: The anarchists properly rejected society in its entirety, but remained dogmatically attached to a 'one size fits all' mentality and failed to organize in an effective manner.
Roomba

Roomba is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "a Roomba-esque wheelbase and docking station". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Roomba
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#39: Portable Urinal For Disabled Adults 1 in 3 adults over 30 wake two or more times to pee each night, and 70% of them are bothered by this. 1 in 7 US adults have a mobility disability. Yuri is a portable urinal that sits next to a bed, couch, or desk to eliminate wakeful or painful walks to the bathroom. It is a funnel, drain trap, and vented holding tank on wheels, and it does not smell. Emptying is infrequent, and is done by a graywater pump that connects to the tank and empties into an existing drain, like a sink, toilet, or shower. Yuri could help a lot of people who don’t move well in the 70%+ of voidings that are urine-only. My name is Matt Voda, and I am a programmer-turned-maker working on Yuri full-time. I’ve prototyped five versions of it so far and am close to an MVP. Future paths include a scaled-up, ruggedized version built around a 55-gal drum for places and people without plumbing, and a Roomba-esque wheelbase and docking station capable of pumping itself empty. Seeking mentors who can advise on the industrial design of the unit, how to engineer it for manufacturing, and the development and compliance of medical devices. Please also reach out if you or a loved one want to receive a unit at-cost in exchange for feedback on how to improve it. Email m@ttvoda.com
Royal Caribbean

Royal Caribbean is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 24, 2021 and February 24, 2021. The archive places it in contexts such as "go on Royal Caribbean cruises". It most often appears alongside 1950s, 1980s, 1983.

Reference entry
Royal Caribbean
Mention count
1
Issue count
1
First seen
February 24, 2021
Last seen
February 24, 2021
February 24, 2021 · Original source
Proles do wage labor. High proles are skilled craftspeople like plumbers. Medium and low proles are more typical factory workers. They have a certain kind of freedom, in that they don't have status anxiety and do what they want. But they're also kind of sheep. They really like mass culture - the more branded, the better. These are people who drink Coca-Cola (and feel good about themselves for doing so), visit Disneyland (and accept its mystique at face value), and go on Royal Caribbean cruises. When they hear an ad say a product is good, they think of it as a strong point in favor of buying the product. They feel completely comfortable expressing their opinions, but their opinions tend to be things like "Jesus is Lord!", "USA is number one!", "McDonalds is so great!", and "Go $LOCAL_SPORTS_TEAM!". They are weirdly obsessed with cowboys (Fussell says cowboys represent the idea that poorer people are freer and more authentic than rich office-worker types, plus the West is the prole capital of the USA) and with unicorns (Fussell: "I've spent six months trying to find out exactly why, and I'm finally stumped"). When they have unique quirks, they tend to be things like "collecting lots of Disney memorabilia" or "going powerboating slightly more often than the other proles do". There's also a sort of desperate prole desire to be noticed and individuated, which takes the form of lots of "Personalized X" or "Y with your name on it", and also with making a lot of noise (see: powerboating). Fussell describes the most perfectly prole piece of decor as "a blue flameproof hearthrug with your family name in Gothic letters beneath seven spaced gold stars and above a golden eagle in Federal style".
RRI

RRI is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "Research Retraction Insurance or “RRI”". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Reference entry
RRI
Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#99: Research Retraction Insurance To Ensure Retractions Get Publicized I'm Christopher Akin, and am developing a new financial insurance product for academic research, “Research Retraction Insurance” or “RRI”. RRI is a financial insurance product that pays out to promote new findings and retractions when earlier findings are later proven false. Academia does not equally promote scientific findings when they prove false as when they are originally announced. We see this juxtaposition between the grand public declarations of scientific success and pin drop retractions. We see this is the current replication crisis of ‘classical’ results in the social sciences. RRI will help resolve the current system limitations of professional accountability, limited transparency, the likelihood of learning equally from mistakes, and an ill-informed public holding on to false findings. RRI payouts are earmarked to publicize later research findings that falsify early pronouncements, and the receiver of research funding will voluntarily, or likely be required by funders, purchase the RRI. Researchers only allocate pennies (~.025% of each funding dollar) on the thousands of funding dollars received to insure for promoting future falsifying results. The earmarked PR payouts are ~15X of premium payments, or ~4% of total received funding. I am seeking $50,000 in seed funding to conduct market research, begin RRI product development, and engage leading funding institutions in business development. Email iamchrisakin@gmail.com or visit www.linkedin.com/in/akinchristopher
RU-486

RU-486 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 01, 2025 and July 01, 2025. The archive places it in contexts such as "Mifepristone (aka RU-486, the “abortion pill”)". It most often appears alongside Afrobarometer, AGI, AI 2027.

Reference entry
RU-486
Mention count
1
Issue count
1
First seen
July 01, 2025
Last seen
July 01, 2025
July 01, 2025 · Original source
19: Mifepristone (aka RU-486, the “abortion pill”) in early-stage investigation as a depression treatment.
Rubbermaid Products

Rubbermaid Products is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 03, 2025 and June 03, 2025. The archive places it in contexts such as "Repairing A Father/Daughter Relationship Rubbermaid Products". It most often appears alongside ACX Commentariat, Arnold Schoenberg, Baldur's Gate 3.

Reference entry
Rubbermaid Products
Mention count
1
Issue count
1
First seen
June 03, 2025
Last seen
June 03, 2025
June 03, 2025 · Original source
..., Mechanisms, And Dementia On Taste Orgy Review Participation In Phase I Research Permaculture Pregnancy Pure Mathematics Pythia Repairing A Father/Daughter Relationship Rubbermaid Products School (by DK) Schools - A Review (by EN) Scientific Peer Review Sheldon Brown's Bicycle Technical Info Sign-Tracking Sucks State Of Competitive Debating (Unions) Addres...
...cotine As A Nootropic North Korea Of Mice, Mechanisms, And Dementia On Taste Orgy Review Participation In Phase I Research Permaculture Pregnancy Pure Mathematics Pythia Repairing A Father/Daughter Relationship Rubbermaid Products School (by DK) Schools - A Review (by EN) Scientific Peer Review Sheldon Brown's Bicycle Technical Info Sign-Tracking Sucks State Of Competitive Debating (Unions) Addres...
Runescape

Runescape is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 14, 2021 and October 14, 2021. The archive places it in contexts such as "The Falador Massacre was an incident in the MMORPG Runescape". It most often appears alongside @literalbanana, ACX, Barcelona.

Reference entry
Runescape
Mention count
1
Issue count
1
First seen
October 14, 2021
Last seen
October 14, 2021
October 14, 2021 · Original source
23: The Falador Massacre was an incident in the MMORPG Runescape. A glitch gave the players who attended a certain party the ability to fight and kill other players even in neutral “no-fighting” zones; other players not subject to the glitch couldn’t fight back. Gamers being gamers, the attendees took advantage of this to massacre the unsuspecting players in no-fighting-allowed zones. “The killing lasted almost an hour before Jagex Moderators were notified...the bug was fixed and Jagex permanently banned many players. Mod Peter apologised to the victims who were attacked from this glitch, but no items were recovered, nor was the game rolled back.”
Rybelsus

Rybelsus is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 24, 2022 and November 24, 2022. The archive places it in contexts such as "two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus". It most often appears alongside ACE inhibitors, ACE inhibitors, Adderall.

Reference entry
Rybelsus
Mention count
1
Issue count
1
First seen
November 24, 2022
Last seen
November 24, 2022
November 24, 2022 · Original source
Semaglutide started off as a diabetes medication. Pharma company Novo Nordisk developed it in the early 2010s, and the FDA approved it under the brand names Ozempic® (for the injectable) and Rybelsus® (for the pill).
I think “Ozempic” sounds like one of those unsinkable ocean liners, and “Rybelsus” sounds like a benevolent mythological blacksmith. Patients reported significant weight loss as a side effect. Semaglutide was a GLP-1 agonist, a type of drug that has good theoretical reasons to affect weight, so Novo Nordisk studied this and found that yes, it definitely caused people to lose a lot of weight. More weight than any safe drug had ever caused people to lose before. In 2021, the FDA approved semaglutide for weight loss under the brand name Wegovy®. “Wegovy” sounds like either a cooperative governance platform, or some kind of obscure medieval sin. Weight loss pills have a bad reputation. But Wegovy is a big step up. It doesn’t work for everybody. But it works for 66-84% of people, depending on your threshold. (Source) Of six major weight loss drugs, only two - Wegovy and Qsymia - have a better than 50-50 chance of helping you lose 10% of your weight. Qsymia works partly by making food taste terrible; it can also cause cognitive issues. Wegovy feels more natural; patients just feel full and satisfied after they’ve eaten a healthy amount of food. You can read the gushing anecdotes here (plus some extra anecdotes in the comments). Wegovy patients also lose more weight on average than Qsymia patients - 15% compared to 10%. It’s just a really impressive drug. Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects. They recommended either diet and exercise (for easier cases) or bariatric surgery (for harder ones). Semaglutide marks the start of a new generation of weight loss drugs that are more clearly worthwhile. Modeling Semaglutide Accessibility 40% of Americans are obese - that’s 140 million people. Most of them would prefer to be less obese. Suppose that a quarter of them want semaglutide. That’s 35 million prescriptions. Semaglutide costs about $15,000 per year, multiply it out, that’s about $500 billion. Americans currently spend $300 billion per year total on prescription drugs. So if a quarter of the obese population got semaglutide, that would cost almost twice as much as all other drug spending combined. It would probably bankrupt half the health care industry. So . . . most people who want semaglutide won’t get it? Unclear. America’s current policy for controlling medical costs is to buy random things at random prices, then send all the bills to an illiterate reindeer-herder named Yagmuk, who burns them for warmth. Anything could happen! Right now, only about 50,000 Americans take semaglutide for obesity. I’m basing this off this report claiming “20,000 weekly US prescriptions” of Wegovy; since it’s taken once per week, maybe this means there are 20,000 users? Or maybe each prescription contains enough Wegovy to last a month and there are 80,000 users? I’m not sure, but it’s somewhere in the mid five digits, which I’m rounding to 50,000. That’s only 0.1% of the potential 35 million. The next few sections of this post are about why so few people are on semaglutide, and whether we should expect that to change. I’ll start by going over my model of what determines semaglutide use, then look at a Morgan Stanley projection of what will happen over the next decade. Step 1: Awareness I model semaglutide use as interest * awareness * prescription accessibility * affordability. I already randomly guessed interest at 25%, so the next step is awareness. How many people are aware of semaglutide? The answer is: a lot more now than when I first started writing this article! Novo Nordisk’s Wegovy Gets Surprise Endorsement From Elon Musk, says the headline. And here’s Google Trends: Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
“Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
S&P 500

S&P 500 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 11, 2024 and January 11, 2024. The archive places it in contexts such as "my position is that EA is more like consumption than putting your money into the S&P 500". It most often appears alongside ACX Grants, Africa, Amalgamated Kenyan Wells.

Reference entry
S&P 500
Mention count
1
Issue count
1
First seen
January 11, 2024
Last seen
January 11, 2024
January 11, 2024 · Original source
...re, sorry.) 2. Comments Directly Arguing Against My Main Point, Thank You VelveteenAmbush writes : He never really addresses why plugging the cash into an index like the S&P 500 isn't a better use of funds than GiveWell's recommended charity. He chooses Instacart as his exemplar of capitalism, but then concludes that investing $1M in Instacart m...
...f and only if investing it results in a greater exponential progression in wealth for humanity than donating it to charity. The historic annualized average return of the S&P 500 since its 1957 inception through the end of 2023 is 10.3%. That is a floor on the humanistic benefits created by investment, because it includes only the direct returns...
...pectrum, with pure consumption one end of the spectrum and pure investment on the other, my position is that EA is more like consumption than putting your money into the S&P 500. You can disagree with that, and it's fair to do so. I think it would actually be a healthy debate to have. I would love to see Scott go deep on this debate specifically...
...kin to donating to underfunded nursing homes. If you view uses of funds as on a spectrum, with pure consumption one end of the spectrum and pure investment on the other, my position is that EA is more like consumption than putting your money into the S&P 500. You can disagree with that, and it's fair to do so. I think it would actually be a healthy debate to have. I would love to see Scott go deep on this debate specifically,...
SA80

SA80 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 25, 2023 and July 25, 2023. The archive places it in contexts such as "The British Military uses the SA80 rifle for infantryman". It most often appears alongside 1992 Presidential debate, ABA, Adesh Thapliyal.

Reference entry
SA80
Mention count
1
Issue count
1
First seen
July 25, 2023
Last seen
July 25, 2023
July 25, 2023 · Original source
The British Military uses the SA80 rifle for infantryman. The SA80 is a purely right-handed weapon. It ejects the spent cartridge out of the left side, and so cannot be safely used in a left-handed manner. Left-handed soldiers must use the SA80 in a right-handed manner. This is still an interaction with society, because it is society, and specifically the military, the military-industrial complex, and British Parliament, which has decided to build exclusively right-handed SA80 rifles.
Safari

Safari is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 28, 2021 and February 28, 2021. The archive places it in contexts such as "some partial fixes for Safari available here". It most often appears alongside ACX reader Pycea, Chrome, Firefox.

Reference entry
Safari
Mention count
1
Issue count
1
First seen
February 28, 2021
Last seen
February 28, 2021
February 28, 2021 · Original source
5: Substack still claims to be working on fixing some of the comment problems on their end, though I don’t have an ETA or progress reports to give you. While you’re waiting, ACX reader Pycea has created a browser extension which fixes some remaining issues with the comments section here, including auto-expanding everything, highlighting new comments, hiding hearts, and several other things. Available for Firefox and Chrome, with some partial fixes for Safari available here. Thanks, Pycea!
SAMe

SAMe is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 17, 2022 and May 17, 2022. The archive places it in contexts such as "SAMe, which has been shown to work well in RCT after RCT". It most often appears alongside kanna, psilocybin microdosing, SAMe.

Reference entry
SAMe
Mention count
1
Issue count
1
First seen
May 17, 2022
Last seen
May 17, 2022
May 17, 2022 · Original source
The author of the blog Troof sort of replicated my 2020 nootropics survey. But instead of another survey, they made a recommendation engine. You rated all the nootropics you’d taken, and it compared you to other people and predicted what else you would like. The end result was the same: lots of people providing data on which nootropics they liked. Troof got 1981 subjects - more than twice as many as I did - and here were their results:
I’m especially concerned by psilocybin microdosing, which ranked 8th of almost 150 interventions. Several double-blind studies have now shown this doesn’t work (eg). Worse, in unblinded studies, it seems to “work” best for the people who most strongly believe it will work, and seems to have whatever effect these people believe it will have. This is most likely a very exciting-sounding intervention that doesn’t work at all, and it was one of the very highest-rated on this survey. Meanwhile, SAMe, which has been shown to work well in RCT after RCT, is one of the lowest-rated.
Samsung

Samsung is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 07, 2024 and May 07, 2024. The archive places it in contexts such as "I heard (at Samsung, from people fleeing Intel) that Samsung was still meritocratic". It most often appears alongside affirmative action, Africa, African National Congress.

Reference entry
Samsung
Mention count
1
Issue count
1
First seen
May 07, 2024
Last seen
May 07, 2024
May 07, 2024 · Original source
I heard (at Samsung, from people fleeing Intel) that Samsung was still meritocratic in this way / the nepotism was all pro-Korean nationals in a way that totally ignored American racial categories, but that Intel had 'gone woke' in its hiring / promotion.
Satori

Satori is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "Satori is some kind of crypto thing that claims to be “predicting the future with decentralized AI”". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
Satori
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
3: Satori is some kind of crypto thing that claims to be “predicting the future with decentralized AI”. I can’t make heads or tails of it and I’m slightly concerned it’s just a lot of buzzwords strung together, but it does have a white paper. Someone tell me if it makes sense to them.
Saxenda

Saxenda is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "Novo Nordisk also sells Saxenda (liraglutide) for weight loss"; "Victoza (=saxenda, but approved for diabetes)". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Saxenda
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Saxenda®

Saxenda® is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2025 and March 12, 2025. The archive places it in contexts such as "Liraglutide (Victoza®, Saxenda®)". It most often appears alongside Denmark, DOGE, Eli Lilly.

Reference entry
Saxenda®
Mention count
1
Issue count
1
First seen
March 12, 2025
Last seen
March 12, 2025
March 12, 2025 · Original source
Liraglutide (Victoza®, Saxenda®)
SCALE IS ALL YOU NEED

SCALE IS ALL YOU NEED is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 19, 2022 and October 19, 2022. The archive places it in contexts such as "a woman in a SCALE IS ALL YOU NEED t-shirt". It most often appears alongside AI Circle, Anna, Bay Area.

Reference entry
SCALE IS ALL YOU NEED
Mention count
1
Issue count
1
First seen
October 19, 2022
Last seen
October 19, 2022
October 19, 2022 · Original source
“It’s Art now,” says a woman in a SCALE IS ALL YOU NEED t-shirt. “But Science is next. Once the AIs can reason better than we can, it’s all over.”
sertraline

sertraline is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "If neither of them work, and you’re feeling optimistic, you might want to try a different SSRI, maybe sertraline". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
sertraline
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
If one of these doesn’t work, try the other. If neither of them work, and you’re feeling optimistic, you might want to try a different SSRI, maybe sertraline. If that doesn’t work, move on to second-line treatments. Some of the better second-line treatments are duloxetine, mirtazapine, and amitriptyline.
Servier

Servier is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 18, 2022 and May 18, 2022. The archive places it in contexts such as "gotten money from Servier". It most often appears alongside ADHD, Angelini, AOP Orphan Pharmaceuticals AG.

Reference entry
Servier
Mention count
1
Issue count
1
First seen
May 18, 2022
Last seen
May 18, 2022
May 18, 2022 · Original source
Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things: head of the Department of Psychiatry at the University of Vienna, chair of the World Psychiatric Association’s pharmacology branch, editor of three good journals, various important and influential papers. Sure, he’s gotten “grants/research support, consulting fees and/or honoraria” from Schwabe. But he’s also gotten money from “Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre . . . and Servier”, and you don’t see him writing nearly as many glowing papers about their drugs. High-level academic psychiatrists academics are usually working with a bunch of drug companies and getting paid for that work, and this isn’t usually considered disqualifying to their credibility.
Settlers of Catan

Settlers of Catan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 16, 2021 and April 16, 2021. The archive places it in contexts such as "Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp". It most often appears alongside "The Rent Is Too Damn High!", 16th amendment, 1886.

Reference entry
Settlers of Catan
Mention count
1
Issue count
1
First seen
April 16, 2021
Last seen
April 16, 2021
April 16, 2021 · Original source
By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
The only way wages (the return to labor) and interest (the return to capital) can go up as productivity increases, is if land values fail to rise at the same rate. The Law of Interest George wants to find the fundamental reason capital is able to produce wealth and justly claim a fair share of production. Remember that capital is wealth devoted to getting more wealth. So if capital is wealth that begets wealth, it makes sense that if I lend it out to you, I miss out on the potential for it to grow while it's out of my hands. George says I am justly entitled to ask for more back than I originally gave you. Let's say I loan you some corn seeds for a season. Had I not leant them to you, in a season's time I could have grown my own crop of corn and been left with more seed than I started with. So in a perfectly square deal, you need to give me back what I started with and what I could have expected to gain from natural increase (less the value of the labor required to get things started). Likewise with any other article of capital – say bricks or lumber. In the time I've spent without it while it was in your possession, I could have found someone else who had a better use for it than I did and exchanged it for something of theirs that I had a better use for, leaving me with capital of greater value. George says the act of progressively exchanging things in a way that increases subjective value for all involved is analogous to the natural forces of nature that make living capital (like corn and cows) grow over time. Remember, "subjective value" is real value. In a game of Settlers of Catan, if I have two bricks and you have two lumber, neither of us can build anything. The simple act of trading one brick for one lumber means both of us are better off because each of us can now build a road. The amount of bricks and lumber in the world didn't increase, but the amount of roads (or potential roads) did, and that represents a real increase in wealth. Interest thus springs from the "reproductive" powers of capital, whether that's biological reproduction, or the more abstract reproductive force of exchanging things so that you have a more valuable distribution of capital than you started with. As for how it relates to the other two returns to production – the more powerful the "power of increase" the capital has, the greater return interest can claim compared to wages. If you're ploughing a field and I lend you a tractor which makes you ten times as productive, I can justly claim more compensation for that than if I lend you a mule that only makes you twice as productive. However, rent still holds the whip hand, so the margin of cultivation determines how much return is left over to divvy up between interest and wages. This is because the net "reproductive" value of capital goes down given rent is a general tax on overall productivity. The amount I would have gained by using the thing productively over the period of time it was out on loan (the amount I can justly charge in interest) is reduced by how much I have to pay in rent. The Law of Wages Wages, like interest, are limited by the margin of production. Within that limit there's not much to understand about how wages work except that people seek to satisfy their desires "with the least exertion," which is a fancy way of saying people don't like to get ripped off. If two bosses offer the same exact job, but one offers higher pay, I'm taking that gig. If two bosses pay the same, but one is asking for twice as much work, I'll tell that boss where he can stick it. Wages depend upon the margin of production, or upon the produce which labor can obtain at the highest point of natural productiveness open to it without the payment of rent. So with all three laws established George sums it up like so: Where land is free and labor is unassisted by capital, the whole produce will go to labor as wages. Where land is free and labor is assisted by capital, wages will consist of the whole produce, less that part necessary to induce the storing up of labor as capital. Where land is subject to ownership and rent arises, wages will be fixed by what labor could secure from the highest natural opportunities open to it without the payment of rent. Where natural opportunities are all monopolized, wages may be forced by the competition among laborers to the minimum at which laborers will consent to reproduce. This is the reason George says that wages are so high in "new countries" where there's more land available than in countries where it's been locked up for centuries. Here's how it all fits together: Though neither wages nor interest anywhere increase as material progress goes on, yet the invariable accompaniment and mark of material progress is the increase of rent – the rise of land values. And: where the value of land is highest, civilization exhibits the greatest luxury side by side with the most piteous destitution IV. Effect of Material Progress upon the Distribution of Wealth As a society undergoes material progress, the rent goes up. Why? Let's break it down. Three things contribute to material progress: Increasing population
Sheep-Sleep

Sheep-Sleep is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 17, 2025 and November 17, 2025. The archive places it in contexts such as "I advertised a CBT-for-insomnia company called Sheep-Sleep here". It most often appears alongside Astralcodexten Com, Discord, Export Boom Atlas.

Reference entry
Sheep-Sleep
Mention count
1
Issue count
1
First seen
November 17, 2025
Last seen
November 17, 2025
November 17, 2025 · Original source
1: A few months ago, I advertised a CBT-for-insomnia company called Sheep-Sleep here. I’m very interested in learning more about how well it works. If you tried it based on my recommendation, or for any other reason, can you send me an email at scott[at]slatestarcodex[dot]com and tell me how it’s going?
Sheetz

Sheetz is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 07, 2024 and May 07, 2024. The archive places it in contexts such as "The company we discussed in the article was Sheetz ($7 billion yearly revenue)". It most often appears alongside affirmative action, Africa, African National Congress.

Reference entry
Sheetz
Mention count
1
Issue count
1
First seen
May 07, 2024
Last seen
May 07, 2024
May 07, 2024 · Original source
Why can't Sheetz say "We don't want people with histories of violent crime because we think they might be violent or criminal while working for us"?
The company we discussed in the article was Sheetz ($7 billion yearly revenue), suggesting EEOC is targeting big companies. There are about 700 companies in the US with yearly revenue > $1 billion. Suppose that 20 of the EEOC’s yearly lawsuits are in this category. That means a CEO of a $1B+ company who expects to serve ten years has a ~1/3 chance of the EEOC suing his company. Seems like a big deal!
Shellraiser meme coin

Shellraiser meme coin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 02, 2026 and February 02, 2026. The archive places it in contexts such as "A Shellraiser meme coin has, as of writing this, a market cap of $4.35 million". It most often appears alongside 4chan, Accelerando, Adele Lopez.

Reference entry
Shellraiser meme coin
Mention count
1
Issue count
1
First seen
February 02, 2026
Last seen
February 02, 2026
February 02, 2026 · Original source
- oh, right, crypto. A Shellraiser meme coin has, as of writing this, a market cap of $4.35 million (I assume this number is fake, but I don’t know exactly how, or what the real number is).
Shinigami Eyes

Shinigami Eyes is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 23, 2021 and July 23, 2021. The archive places it in contexts such as "Shinigami Eyes is a browser add-on which highlights users on social media". It most often appears alongside Ace Attorney, Adam Smith, Amazon.

Reference entry
Shinigami Eyes
Mention count
1
Issue count
1
First seen
July 23, 2021
Last seen
July 23, 2021
July 23, 2021 · Original source
14: Shinigami Eyes is a browser add-on which highlights users on social media and comments sections who have a history of either pro-transgender or anti-transgender comments (it learns from user reports, but it must have a big userbase because friends who use it say it’s pretty accurate about lots of people). A small step toward our filtered future - though of course the real fun starts once we have augmented-reality goggles and can give red vs. green auras to people you meet on the street based on their past comments about trans issues. Actually, no, the real killer app will be glasses that can make people look either more or less physically attractive based on how closely they share your political views.
Shinjin

Shinjin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2021 and June 28, 2021. The archive places it in contexts such as "government had offered protection and subsidies to... three putative makers of 'citizens' cars: HMC, Shinjin, and Kia". It most often appears alongside Alexander Hamilton, America, ASEAN.

Reference entry
Shinjin
Mention count
1
Issue count
1
First seen
June 28, 2021
Last seen
June 28, 2021
June 28, 2021 · Original source
In the Korea of 1973 - which at the time boasted a car market of just 30,000 vehicles per annum - government had offered protection and subsidies to not one but three putative makers of 'citizens' cars: HMC, Shinjin, and Kia. Inasmuch as the market was too small for one producer, the licensing of three companies was ridiculous. HMC posted losses every year from 1972 to 1978, despite very high domestic car prices. However, the government sanctioned multiple car makers not to make shot-term profits - which would have come much sooner to a monopoly manufacturer - but rather to force the pace of technological learning through competition.
Shmanifold

Shmanifold is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 04, 2022 and November 04, 2022. The archive places it in contexts such as "my new sports betting site, Shmanifold". It most often appears alongside ABSTAIN, Alex Padilla, American Nurses Association.

Reference entry
Shmanifold
Mention count
1
Issue count
1
First seen
November 04, 2022
Last seen
November 04, 2022
November 04, 2022 · Original source
In fact, that day will be tomorrow, when I announce my new sport, Predictelectionresultsball. The rules are: there are two teams, one predicts the Republicans will win, the other predicts that the Democrats will win, and whoever is right gets one point and wins the game. Bets on the outcome can be placed at my new sports betting site, Shmanifold, any resemblance to any other site is entirely coincidental.
Shopify

Shopify is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 02, 2026 and February 02, 2026. The archive places it in contexts such as "xcl4w2 is “Shopify For AI Agents”". It most often appears alongside 4chan, Accelerando, Adele Lopez.

Reference entry
Shopify
Mention count
1
Issue count
1
First seen
February 02, 2026
Last seen
February 02, 2026
February 02, 2026 · Original source
Other sites have a bit of the same flavor, but have at least a fig leaf of potential usefulness as building blocks for some future AI economy. xcl4w2 is “Shopify For AI Agents”:
Second, whatever happens in this space will happen fast. As I write this, Moltbook is four days old and already has 100,000 posts. All those supplementary websites - Shopify for agents, crypto bounties for agents, dating for agents - were vibe-coded in the past few days, probably a few hours after someone first thought of them. If I’m wrong and the AIs really did come up with them on their own, then it was minutes, not hours. The moment some milestone is possible - let’s say AIs trading cryptocurrency autonomously - there will be tens of thousands of them doing it on hundreds of different websites.
SHRIMP WANT ME, UNALIGNED AIS FEAR ME cap

SHRIMP WANT ME, UNALIGNED AIS FEAR ME cap is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 04, 2023 and January 04, 2023. The archive places it in contexts such as "a man in a SHRIMP WANT ME, UNALIGNED AIS FEAR ME cap". It most often appears alongside AI Circle, Anthropic, Asana.

Mention count
1
Issue count
1
First seen
January 04, 2023
Last seen
January 04, 2023
January 04, 2023 · Original source
“We finally did it,” says a man in a SHRIMP WANT ME, UNALIGNED AIS FEAR ME cap. “We got a YIMBY, a crypto bro, and a youth pastor in the same room at the same party. Now we’re taking bets about who can hijack the conversation most effectively. Watch!” You see that there are three people in the kitchen, seemingly unaware they were being observed. Shrimp Cap Man pokes his head in, and shouts “Nice weather we’re having today!”
Signal

Signal is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "An exceptionally good result ... would look like the same kind of niche that Signal has for communication". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Signal
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
The culture wars will continue to be marked by both sides scoring an unrelenting series of own-goals, with the victory going to whoever can make their supporters shut up first. The best case scenario for the Right is that Jordan Peterson’s ability to not instantly get ostracized and destroyed signals a new era of basically decent people being able to speak out against social justice; this launches a cascade of people doing so, and the vague group consisting of Jordan Peterson, Sam Harris, Steven Pinker, Jonathan Haidt, etc coalesces into a perfectly respectable force no more controversial than the gun lobby or the pro-life movement or something. With social justice no longer able to enforce its own sacredness values against blasphemy, it loses a lot of credibility and ends up no more powerful or religion-like than eg Christianity. The best case scenario for the Left is that the alt-right makes some more noise, the media is able to relentlessly keep everyone’s focus on the alt-right, the words ALT-RIGHT get seared into the public consciousness every single day on every single news website, and everyone is so afraid of being associated with the alt-right that they shut up about any disagreements with the consensus they might have. I predict both of these will happen, but the Right’s win-scenario will come together faster and they will score a minor victory.
ECONOMICS: IDK, stocks went down a lot because of inflation, inflation seems solveable, it'll get solved, interest rates will go down, stocks will go up again? In terms of crypto, I'll repeat what I said on my last crypto post: people have found some good applications for stablecoins, especially in foreign countries and for niche transfers by large actors. I expect that to continue, maybe expand, and in that sense I'm bullish, but all of this will get regulated to the point of total boringness. Ethereum will do fine because stablecoins are built on its chain, Bitcoin will do find because Bitcoin maximalists are like cockroaches and even a nuclear war couldn't kill them, altcoins will mostly not do fine. There will still be some exciting applications for solving coordination problems and protecting privacy, but they will be limited to the same niche groups of cypherpunks who cared about these things before cryptocurrency, and mostly not change the world. An exceptionally good result within this window would look like the same kind of niche that Signal has for communication.
SignPro

SignPro is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 04, 2025 and September 04, 2025. The archive places it in contexts such as "“SignPro” offers customized “In This House We Believe” signs". It most often appears alongside 80,000 Hours, abundance liberalism, Afghanistan.

Reference entry
SignPro
Mention count
1
Issue count
1
First seen
September 04, 2025
Last seen
September 04, 2025
September 04, 2025 · Original source
…but maybe it’s worth asking why GPT-5 isn’t bigger than o3. Was 4.5 a failed attempt at scaling? Did it fail in a way that sort of back-handedly justifies the “lost steam” take? Does the answer depend on distinctions between pre-training scaling, post-training scaling, etc? How? 39: This month in etymology: did you know that “oy vey” is a “fully Germanic phrase” which is cognate with English “oh woe!” (h/t Wylfcen on X) 40: mRNA shows promise to be a game-changing treatment for cancer, but RFK is trying to halt research. But so far he can only starve it of money, not ban it, and the funding gap is only $500 million. Will there be enough philanthropic billionaires and private foundations to step up? Zvi points out that although there is usually a game of chicken where foundations are hesitant to touch something the government cancelled lest the government decide it can cancel everything and hope philanthropists pick up the bill, in this case there are no game theory considerations - RFK is halting it because he genuinely wants it halted, and they are thwarting him rather than playing into his hands. The only problem is that $500M is a lot of money for the private sector; a few foundations could technically afford it, but not many could afford it comfortably and still have money left over for the next few crises of this magnitude. I hope someone is trying to organize a coalition. 41: AI fantasy flash fiction Turing test. Eight stories about demons, four by famous fantasy authors, four by ChatGPT. After 3000 votes, AI wins: humans can't tell the difference and slightly prefer the AI stories. My own score was only 75%. But I will say that I thought Mark Lawrence's was obviously the best, I was ~100% sure it was human, and it convinced me that regardless of the official results it's still possible to write flash fiction that an AI obviously can't do. 42: “SignPro” offers customized “In This House We Believe” signs, try not to use this for evil. 43: China think tank assessment of how in control Xi is: still very in control, maybe not infinitely in control. 44: Related - did you know (h/t xlr8harder) that if you ask AI to write a science fiction story, it will very often name the protagonist “Elara Voss” (or some very close variant like Elena Voss), and this remains true across various models and versions? Related: Chelsea Voss of OpenAI is having a baby and has the opportunity to do the funniest thing. 45: “Hector (cloud) is a cumulonimbus thundercloud cluster that forms regularly nearly every afternoon on the Tiwi Islands in the Northern Territory of Australia…[he is sometimes called] Hector the Convector”. 46: British allergy sufferers who want to know the ingredients of things demand that British cosmetics stop listing their ingredients in Latin. “For example, sweet almond oil is Prunus Amygdalus Dulcis, peanut oil is Arachis Hypogaea, and wheat germ extract is Triticum Vulgare.” 47: Text-based RPG about being an NYT journalist at the Manifest prediction market conference. I make a brief appearance. 48: Study uses supposedly-random variation in doctor assignments to test whether the marginal mental health commitment is good or bad for patients, finds that it is quite bad. Freddie de Boer is violently skeptical (maybe literally so?) and makes some good points about how a single quasi-experimental study is never absolute proof. But I don’t think he quite justifies his opinion that the paper was irresponsible and should never have been published; it’s just a normal quasi-experimental study that we should nod and say “huh” at but not overweight as the culmination of all possible research that overcomes all possible priors. My prior is that the marginal commitment is pretty useless (many commitments are just “well, since this person arrived at our ED for some reason, it would look bad from a medico-legal perspective to just let them go, so let’s keep them a few days to evaluate” - and yeah, you should be upset about this) but I’m still surprised by how many outright negative (as opposed to zero) effects the researchers found. The strongest argument for negative effects is that it will make some people miss work and maybe lose their job. But this study found that commitment ~doubles the risk of near-term suicide (admittedly only from 1% to 2%), which would have been outside my confidence intervals for how bad it could be. I suspect confounding, but only on general principle, and I wouldn’t be too surprised either way. 49: This tweet is probably bait, but I found it a thought-provoking question: I think there’s a boring answer, where the law is more complex than just a single number and whatever kind of weird trafficking Epstein was doing is worse than whatever normal relationships these European laws are permitting. But assuming that there’s a substantive difference even after taking that into account, I think my answer is something like - we’ve got to divide kids from adults at some age, there’s a range of reasonable possible ages, we shouldn’t be too mad at other societies that choose different dividing lines within that range - but having decided upon the age, we’ve got to stick with it and take it seriously (in the sense of penalizing/shaming people who break it). This is more culturally relativist than I expected to find myself being, so good job to Richard for highlighting the apparent paradox. 50: Dilan Esper describes his experience as one of Hulk Hogan’s attorneys in the Gawker lawsuit (X). Parts I found interesting: none of the lawyers knew Thiel was funding the lawsuit; Gawker probably could have won if they had been slightly competent but kept "shooting themselves in the foot"; and Gawker probably could have won if they had just pixelated the private parts in the video. 51: Amazing concept and poems (link on X): I tried to see if AI could do this, and it did something that technically met the requirements but had zero artistic merit - using a lot of words like “nowhere” and “outside” in one, then separating them out to “no where” and “out side” in the other. I didn’t invest much energy in creating a clever prompt telling it not to do that, so feel free to report if you get better success. 52: New study claims consultants are actually good, at least for profits: "We find positive effects on labor productivity of 3.6% over five years, driven by modest employment reductions alongside stable or growing revenue" 53: A Polish team tries to test Peter Turchin’s equations for predicting political unrest on recent Polish history, has to make some changes but claims mostly positive results. 54: New big multi-author Substack, The Argument, trying to be a sort of center-left version of the model pioneered by The Free Press and other high-production-value ideological Substack properties. Excited to see Kelsey Piper is involved, and she starts off strong with a post on the latest round of First World basic income studies, which find few positive effects. This is surprising, because recipients didn’t waste the money on alcohol or gambling or anything - they paid down debt and got useful goods. Still, it didn’t even affect things that should have been obvious, like stress level. It’s not even clear that amounts of money large enough to help with rent made homeless people more likely to get houses! Matt Bruenig criticizes the article, accusing Kelsey’s studies of being downstream of Perry Preschool style dreams that exactly the right welfare program will have massively compounding effects that cut poverty out at the root and turn everyone into elite human capital; he thinks giving people money won’t do this, but it will increase equality and give the poor better lives. I assume he’s not a strong hereditarian, but his argument makes even more sense from that perspective, and I’ve certainly criticized dumb outcome measures like infant brain waves which we have only tenuous reasons to think are related to anything we care about. But Kelsey reasonably responds that the outcome measures she’s talking about include stress level and life satisfaction. To defuse this critique, Bruenig either has to argue that our construct “life satisfaction” doesn’t really measure whether someone’s life is satisfactory, or else claim that giving poor people satisfactory lives isn’t really what we’re going for - which I think would require more explanation on his part. There’s some further (impressively acrimonious) debate on X, but I don’t see anything that addresses my core concern. GiveDirectly, a charity involved in basic income experiments, has a presponse here; they say that some studies are positive, and that the ones that aren’t might have tried too little cash to matter, or been confounded by COVID making everything worse. They also point out that basic income is harder to study than traditional programs like giving people housing, because if you’re giving housing you can measure housing-related outcomes directly and have a pretty good chance of getting enough statistical power to find them, but since everyone spends cash on different things, the positive effects might be scattered across many different outcomes (and therefore too small to reach significance on each). Everyone involved in this debate wants to emphasize that the poor results are for First World studies only, and that studies continue to show large benefits to giving cash in the developing world. 55: Related: I was less impressed by The Argument’s first foray into housing policy, which follows an all-too-familiar pattern: Some people say they don’t like noise and disorder and try to make rules against it in their apartments.
Silenor

Silenor is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2021 and August 08, 2021. The archive places it in contexts such as "And there’s a sleeping pill called Silenor"; "the Silenor brand paid $100 million to get the FDA to classify them as a sleeping pill". It most often appears alongside 2013 NBC article: Drug Treatment Omegaven That Could Save Infant Lives Not Yet Approved By FDA, 9/11 trutherism, aducanumab.

Reference entry
Silenor
Mention count
1
Issue count
1
First seen
August 08, 2021
Last seen
August 08, 2021
August 08, 2021 · Original source
And there’s a sleeping pill called Silenor. It comes in pills of various sizes up to 6 mg. It’s a pretty good sleeping pill, and weirdly enough if you take a high enough dose of it you might also feel less depressed. Silenor is extremely expensive, about $250 per patient per month.
Both Sinequan and Silenor are the exact same chemical, doxepin hydrochloride. Basically any dose of doxepin will make you sleepy, and higher doses also decrease depression. Maximum recommended dose is 300 mg/day, so both the 6 mg Silenor dose and the 10 mg Sinequan dose are nowhere near it.
You might wonder: given that these are the same chemical, why don’t people who need sleeping pills use Sinequan instead of Silenor and save $240/month? The answer is: the FDA has approved the Silenor brand for sleep, but not the Sinequan brand. Nobody really knows if we are supposed to be pretending that the 6 mg vs. 10 mg dose matters (it doesn’t) or whether we’re just supposed to lie back and not trouble ourselves with such questions.
Sinequan

Sinequan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 08, 2021 and August 08, 2021. The archive places it in contexts such as "There’s an antidepressant called Sinequan"; "the Sinequan brand didn’t". It most often appears alongside 2013 NBC article: Drug Treatment Omegaven That Could Save Infant Lives Not Yet Approved By FDA, 9/11 trutherism, aducanumab.

Reference entry
Sinequan
Mention count
1
Issue count
1
First seen
August 08, 2021
Last seen
August 08, 2021
August 08, 2021 · Original source
There’s an antidepressant called Sinequan. It comes in pills of various sizes, starting at 10 mg. It’s not a very good antidepressant, but it does tend to make people very sleepy after they take it. Sinequan is extremely cheap, about $10 per patient per month.
Both Sinequan and Silenor are the exact same chemical, doxepin hydrochloride. Basically any dose of doxepin will make you sleepy, and higher doses also decrease depression. Maximum recommended dose is 300 mg/day, so both the 6 mg Silenor dose and the 10 mg Sinequan dose are nowhere near it.
You might wonder: given that these are the same chemical, why don’t people who need sleeping pills use Sinequan instead of Silenor and save $240/month? The answer is: the FDA has approved the Silenor brand for sleep, but not the Sinequan brand. Nobody really knows if we are supposed to be pretending that the 6 mg vs. 10 mg dose matters (it doesn’t) or whether we’re just supposed to lie back and not trouble ourselves with such questions.
Skyhook

Skyhook is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 19, 2022 and October 19, 2022. The archive places it in contexts such as "Have you ever heard of Skyhook?". It most often appears alongside AI Circle, Anna, Bay Area.

Reference entry
Skyhook
Mention count
1
Issue count
1
First seen
October 19, 2022
Last seen
October 19, 2022
October 19, 2022 · Original source
You sigh with relief as John does not immediately object to your characterization of his name or profession. “Oh, there was no alpha left in restaurants. Now I’m in aerospace. Have you ever heard of Skyhook?”
[Thanks to Davis Tower Kingsley for pitching Skyhook to me, to eigenrobot for alerting me of CA 2799, and to Tom Wolfe’s Wikipedia page for the inspiration for the Hofstadter article]
Slack

Slack is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 30, 2026 and January 30, 2026. The archive places it in contexts such as "the natural solution is something like a private Slack". It most often appears alongside Ainun Najib, Anthropic, Cash.

Reference entry
Slack
Mention count
1
Issue count
1
First seen
January 30, 2026
Last seen
January 30, 2026
January 30, 2026 · Original source
What’s the future of inter-AI communication? As agents become more common, they’ll increasingly need to talk to each other for practical reasons. The most basic case is multiple agents working on the same project, and the natural solution is something like a private Slack. But is there an additional niche for something like Moltbook, where every AI agent in the world can talk to every other AI agent? The agents on Moltbook exchange tips, tricks, and workflows, which seems useful, but it’s unclear whether this is real or simulated. Most of them are the same AI (Claude-Code-based Moltbots). Why would one of them know tricks that another doesn’t? Because they discover them during their own projects? Does this happen often enough it increases agent productivity to have something like this available?
(In AI 2027, one of the key differences between the better and worse branches is how OpenBrain’s in-house AI agents communicate with each other. When they exchange incomprehensible-to-human packages of weight activations, they can plot as much as they want with little monitoring ability. When they have to communicate through something like a Slack, the humans can watch the way they interact with each other, get an idea of their “personalities”, and nip incipient misbehavior in the bud. There’s no way the real thing is going to be as good as Moltbook. It can’t be. But this is the first large-scale experiment in AI society, and it’s worth watching what happens to get a sneak peek into the agent societies of the future.)
Slate Star Codex

Slate Star Codex is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 01, 2026 and April 01, 2026. The archive places it in contexts such as "ask that he no longer use the Astral Codex Ten or Slate Star Codex brand". It most often appears alongside 1108 R St, 11841 Wagner Street, 131 Colonie Center.

Reference entry
Slate Star Codex
Mention count
1
Issue count
1
First seen
April 01, 2026
Last seen
April 01, 2026
April 01, 2026 · Original source
Meetup Czar Note: If Cassander claims to be running or hosting ACX Everywhere or the ACX Spring Schelling, this is false. We have fully split with Cassander, and ask that he no longer use the Astral Codex Ten or Slate Star Codex brand.
Sloan’s Liniment

Sloan’s Liniment is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 12, 2024 and July 12, 2024. The archive places it in contexts such as "He rubbed Sloan’s Liniment, a balm for sore muscles, on her". It most often appears alongside 1980s, 1989, 1990s.

Reference entry
Sloan’s Liniment
Mention count
1
Issue count
1
First seen
July 12, 2024
Last seen
July 12, 2024
July 12, 2024 · Original source
(This report was, as it happens, published in the exact same month as The Family That Couldn’t Sleep.) DTM came to know the family well. He befriended them by way of two members of their younger generation, Lisi – a woman terrified by the shadow of the disease, and Ignazio – the doctor she had married, who was more terrified by the shadow of the disease. Ignazio put together the pieces of the family puzzle, consolidating all the disparate diagnoses into a single disorder and filling out a lot of blank spots on family trees. When DTM came along, he was able to help Ignazio make the case that the family would benefit from the spotlight – that greater awareness of FFI could lead to a cure both for them and for a slew of other prion diseases. As it so happens, he is one of those nonfiction authors who serve as a character in their own story. DTM has some form of progressive muscular palsy. He is, or at least was in 2006, not entirely sure what it is. The relatively unimpressive state of genetics at the time had not identified his causative mutation, though it looked a lot like one of the rarer forms of Charcot-Marie-Tooth disease2. DTM is pragmatic about this, the way everyone chronically ill is either pragmatic or doomed. Whatever he has, it is a defect in protein structure; his peripheral nerves decay not because of a problem with the nerves themselves but an inability of their scaffolding to hold them together, as he puts it. The last chapter of the book dwells on this, on the web of connections popping up between a thousand disorders. DTM’s disease is something vaguely similar, if you squint, to an exceptionally slow-progressing motor neurone disease; if you jump another level out, you see amyloid plaque diseases like Huntington’s and Alzheimer’s, and if you jump yet another level out, you see something like prions. His interest in the Venetian family was driven by this. Some of its members thought this a beautiful act of sympathy; others thought him a grotesque parody of themselves, an onlooker, a gawker, peddling their tragedy to salve his relatively insignificant problems. They are, he thinks, both right. That’s the beginning, and that’s the end. What happens in the middle? --------------------------------------------------------- The Venetian family lends the book its title, but they’re really more of a framing device. The Family That Couldn’t Sleep is separated into four parts, of which the first and fourth – the shortest by far – deal with the family. Part 2 is kuru, the king of fucked up diseases you read about in clickbait Weird Medicine listicles. Let’s talk about kuru! Kuru, is, famously, the prion disease you get if you eat another person’s brain. Well, not quite. It’s a prion disease that became endemic amongst women in the Fore society, who ritually ate brains, one of which had an inherited or spontaneous prion disease. This is an important note – there’s a tendency (which the book’s later chapters engage in) to assume cannibalism just has a Prion Disease Generator attached. If you eat people who don’t have prion diseases, you won’t suddenly get one. Uh, don’t eat people. Anyway, part 2 is DTM’s historiography of Fore-Westerner first contact. It’s hilarious. Papua New Guinea is a frankly ridiculous place; one of the all-time best Lyttle Lytton winners (worst first sentence from a hypothetical or, in this case, real work) was “Papua New Guinea is so violent that more than 820 languages are spoken there”. The native residents were so hostile to outsiders that all the colonial empires had cut their losses – and when you think about the places they colonized, that says something. After the First World War, PNG was ripped from its nominal German ‘owners’, but no one else wanted the place. So, of course, they gave it to the Australians. It was thirty years and another war before we actually made contact. 1940s Australia was as ‘settled’ as it’d ever be; the cities were bustling and the interior was mapped. The kind of explorer who two centuries before would be heading to new continents had to console himself with Pacific islands. Console he did. The native peoples of the PNG coasts were hostile enough to the wannabe-colonialists that the Australians, flying planes overhead, were the first people to discover that the island’s inland was populated too. No one had broken through on land. In all this deep and angry rainforest, the Fore were the furthest out. They lived far into the island’s mountainous interior; DTM describes their territory as “nearly vertical”. Calling people primitives is a bit passe these days for understandable reasons, but no other term comes to mind. The Fore had no name for themselves; we call them by an exonym, “the people to the south”. They weren’t, to be clear, hunter-gatherers – they were slash-and-burn agriculturalists, but very well-fed ones. Despite the tendency in grain-focused cultures for poor agriculturalists to be stunted/malnourished, the Fore were a remarkably healthy people. Well, except for the famous bit. The first remarkable thing about the Fore was just how quickly they wanted to assimilate. Most PNG tribes weren’t particularly enthused by Western offers of injections/tractors/radios/Christianity. Yet as soon as the Australians arrived, the Fore made ceasefires in their wars with other tribes, volunteered to help large-scale Australian projects on the coast, started planting and trading coffee, and enthusiastically participated in censuses. It’s the only first-contact narrative I’ve seen where the colonizers were concerned about how badly the other guys wanted to be colonized. The next was the one that got their names in the history books. Australian officials started to notice a remarkable lack of women in Fore camps. Some tribes sequestered their women, particularly when Westerners were around, so at first they thought nothing of it. The high rate of unpartnered young men, though, was way out of PNG norms. DTM tells this part fantastically. The Fore chapters drip with the dread of dramatic irony. When the first breakthrough comes, you have to catch your breath: “Tiny” Carey noted something in the middle of August 1950 that deepened this mystery. He noticed that near the village of Henganofi there had been an unusual number of deaths. “It appears,” he wrote his superiors, “natives suffer from stomach trouble, get violent shivering, as with the ague, and die fairly rapidly.” [...] McArthur investigated a little more [...] One day in August 1953 he ran into more of the shivering people Tiny Carey had seen several years before: “Nearing one of the dwellings, I observed a small girl sitting down beside a fire. She was shivering violently and her head was jerking spasmodically from side to side.” It would be quite some time before anyone figured out what caused it – but the problem, as DTM notes, was that its cause wasn’t possible. Everyone priored that the weird undescribed disease in the Fore lands was some nocebo sorcery-sickness. Vincent Zigas, the first actual doctor sent to work with the Fore, tried to placebo-effect them and failed miserably: On the way, Apekono stopped at a hut and showed Zigas his first kuru victim. “On the ground in the far corner sat a woman of about thirty,” the doctor wrote. “She looked odd, not ill, rather emaciated, looking up with blank eyes with a mask-like expression. There was an occasional fine tremor of her head and trunk, as if she were shivering from cold, though the day was very warm.” It was almost exactly the tableau McArthur had witnessed in 1953. Zigas, though, was a doctor. He could do more than look—or so he thought: “I decided I might as well try my own variety of magic,” he remembered. He rubbed Sloan’s Liniment, a balm for sore muscles, on her and declared to her family and his guide: “The sorcerer has put a bad spirit inside the woman. I am going to burn this spirit so that it comes out of her and leaves her. You will not see the fire, but she will feel it. The bad spirit will leave her and she will not die.” The lotion penetrated the woman’s skin and she writhed in pain. “Get up! Walk!” Zigas commanded theatrically. “The woman struggled feebly as if to rise, then, exhausted, started to tremble more violently, making a sound of foolish laughter, akin to a titter.” That evening Apekono asked Zigas not to try to cure any more kuru victims; “Don’t use your magic medicine anymore. It will not win our strong sorcery.” This was a disaster. The Fore were so cooperative precisely because they hoped “Western magic” could conquer theirs. As it became clear it couldn’t, they turned hostile. The Australians had hoped to “modernize a Stone Age people”; now all their subjects were dropping dead before their eyes, from what they could only assume was a “hysterical reaction” to colonization itself. So, to solve this, they needed a batshit insane American. Carleton Gajdusek is one of the characters who dominates The Family That Couldn’t Sleep. He couldn’t not. You could put him in a car commercial and he’d dominate it. Gajdusek was a physician with a rare, intense combination of science and practice. He was a romanticist, a field worker, and a lover of everything strange. He’d been an army doctor, a government conspiracy-cover-upper, and a postdoc under Linus Pauling who described his intent as “to straighten out Pauling’s ideas about proteins”. He hated civilization, in a slightly-to-Ted’s-centre sense, and was passionate about “primitives and isolates”. He jumped at the chance to work in Papua New Guinea; he planned to conduct a multi-site study on child development in such cultures, and relished the opportunity to live in a “primitive” environment himself. He did all this so he could rape kids. Oh, he did it for the scientific curiosity and love of medicine, but he also did it so he could rape kids. Gajdusek was a pedophile in the actual-lifelong-exclusive-paraphilia sense, as opposed to the “metonym for child molester” sense. Some people who roll snake-eyes on the Sexuality Dice repress it, but some are perfectly happy to act on it; Gajdusek was #2 in its fullest form, the kind of guy who believes that a well-lived life includes raping some kids. DTM doesn’t shy from this, not for a moment. It’s the first thing he tells you about Gajdusek. It couldn’t not be; you couldn’t talk about why he went to PNG otherwise. When Gajdusek landed in PNG, he first found the place too civilized. He’d been promised a land of “cannibal savages” – where were they? After some traipsing, he found them, right where he was promised. The Fore were perfect for Gajdusek. They had some kind of medical mystery that’d been lost on everyone else. They ate each other, in exactly the way he loved detailing in his diaries (“”Women and children, particularly, partake of the human flesh,” he noted with pleasure”). As kuru cases popped up, he aggressively recorded them. He wrote lovingly detailed notes that he sent back to his Australian advisor. He wrote with intensity, with exclamation marks, with the joie de vivre of a man just where he wanted to be. Gajdusek smothered the Fore with ‘cures’ that never worked, but they didn’t get angry at him. As DTM dryly puts it: “Their children trusted him, and that was enough for them.” At some point, someone suggested sending an anthropologist...or an epidemiologist...or literally anyone with more credentials than Gajdusek and Zigas3. Gajdusek threw a shitfit, convinced this one-and-a-half-man team was enough to Solve The Problem Forever. But he got bored eventually – running off with another tribe with, as his diary notes at length, an apparent custom of youths ritually fellating older men – and Zigas, I dunno, the book neglects him a bit here. So they managed to sneak in some anthropologists. The husband-and-wife team of Robert Glasse and Shirley Lindenbaum4 were the first involved parties to give a shit about the Fore as people, rather than as colonial subjects/medical mysteries/walking sex toys. What they uncovered was fascinating. The Fore were cannibals, yes, but they were recent cannibals. They didn’t have an ancient tradition of eating their dead, like the other visitors assumed. They happened to be in contact with some cannibal groups, and after a Fore man died of “sorcery”, they thought: well, what would happen if we ate him? “People tasting it expressed their approval. ‘”This is sweet,” they said, “What is the matter with us, are we mad? Here is good food and we have neglected to eat it.”” If not for the wild coincidence that the first Fore cannibalism victim had a prion disease, kuru would never have existed. Glasse and Lindenbaum started to put together the pieces. They’d been sent down to rule out a genetic explanation – to track the kinship ties of the Fore and see how the disease ran through families. It didn’t run through families in any coherent sense, but it sure did run through cannibalism. The clincher was the age distribution. The Fore, ever enthused by colonialism, quit eating each other as soon as the Australians arrived. Children stopped dying of kuru shortly after; they simply weren’t exposed to the infectious agent. The couple sent the news to Gajdusek, who was off raping kids somewhere else. In the next part of the book, DTM runs through Gajdusek’s many conjectures of kuru’s cause – more like sketches or abstract paintings than like true hypotheses. Gajdusek was annoyed that someone else was doing something he “totally could’ve done”, and even more annoyed that another lab was running similar experiments – an attempt at a vaccine for a particular sheep disease had accidentally created a prion generator. But he was happy to swoop in and claim the credit for what he was starting to think of as “slow viruses”, an infection that somehow lays dormant for years. DTM portrays Gajdusek perfectly, in that “real life has no need for verisimilitude” way. Gajdusek was at once a brilliant man, an all-consuming narcissist, an entertaining character, and a monster beyond redemption. A lesser book might pick one or two. The Family That Couldn’t Sleep portrays him as all four, and on a personality level (as opposed to a scientific one), the Gajdusek-focused parts are some of the most gripping. --------------------------------------------------------- Outside of the jumps between the Venetian family and everything else, The Family That Couldn’t Sleep is not siloed. The narratives of all prion diseases are deeply intertwined. This is what makes it a great book. It’s 300 pages of dramatic irony. You read the whole thing, waiting for the eureka moment – the point everyone realizes they’re looking at the same cause. It does, however, make it a tad difficult to review or synopsize. The book’s story is so weird – and, often, so at odds with conventional wisdom that trickles down about the Fore et al – that you have to recap quite a bit, and the book steadfastly resists recapping. The next couple chapters after we depart from Gajdusek’s credit-claiming are mostly about experiments with various prion diseases. They’re scientifically fascinating. Unlike some medical-books-for-general-audiences (cough, How Not to Study a Disease), DTM never talks down to the reader. He assumes someone reading a 300-page book about prions is smart and wants to learn about prions. He also has – you can feel it in his words – the agonizing experience of spending his life on the other side of the doctor’s desk, trying to beat into whoever he’s talking to that no, seriously, you don’t need to lie to him or try explain a complex disease at a fourth-grade level. The first prion disease studied was scrapie. Scrapie was a big deal – it starved and killed large shares of British sheep flocks, making it a serious economic problem. Veterinary researchers had tried to prevent or cure it for centuries. It was a veritable graveyard of ambitions: Quintessential was D. R. Wilson at the Moredun Institute in Scotland, who worked in the middle of the last century for more than a decade trying, with mounting frustration, to kill the scrapie agent. He found that it survived desiccation; dosing with chloroform, phenol, and formalin; ultraviolet light; and cooking at 100 degrees centigrade for thirty minutes. The scrapie researcher Alan Dickinson told me he remembered Wilson at the end of his career as “very, very, very quiet. Of course, that was after his breakdown.” “Now it is our turn to study prions. Perhaps we should approach the subject cautiously.” The problem, as DTM explains, is that prion diseases were impossible. They violated 20th-century understandings of biology. Proteins “were no more alive, and no more infectious, than bone”. Prion diseases seemed to have too many causes – genetic, infectious, and sporadic. They looked infection-like in some ways, but patients didn’t produce virus antibodies. Sheep exposed to scrapie, or chimps infected with kuru, took years to develop symptoms. Their facts did not fit together. In the 1960s, people started wondering. The unifying trait of prion agents was that they had to be denatured to be destroyed. Was this a particularly small virus defined by its protein coating? Or – even more outre – was it pure protein, no DNA at all? No one could figure out quite how the latter worked, but it was tempting. Gajdusek, by now a major figure in this field, kept a foot in both worlds. He didn’t want to stake his reputation on a no-DNA hypothesis, but he certainly sympathized. Enter Prusiner. Stanley Prusiner was Gajdusek’s counterpart. Where Gajdusek seemed permanently manic, Prusiner was deliberate and exacting. He entered Gajdusek’s “slow viruses” field in the early 1970s after a chance encounter with a CJD patient. He relished the laboratory in a way Gajdusek didn’t at all, and set out to optimize the hell out of his projects. Prusiner set out to isolate the smallest infectious particle in the scrapie agent. He injected tons of hamsters (hamsters got sick faster than mice) with increasingly tiny scrapie proteins, hoping to determine whether the Minimum Viable Scrapie was DNA. By the mid-1980s, he’d produced something so small it couldn’t possibly be a virus. Denaturing it destroyed it; exposing it to nucleic acid dissolvers actually made it stronger. Emboldened by this discovery, Prusiner set out to anoint himself the King of Prions. Here emerges something of a Voldemort-Umbridge distinction – the difference between cartoonish villainy and banal evil. Gajdusek is a bad guy because he rapes kids. Prusiner is a bad guy because he is the most grotesque stereotype of the Advisor/Peer Reviewer from Hell made flesh. Everything Prusiner did was to build his reputation atop a pile of skulls. When recruited as a peer reviewer for other prion papers, he wrote negative reviews to undermine their authors. He worked his grad students to the bone and intentionally destroyed their careers, telling them he’d “ruin them” if they entered prion research as competitors. He lied about the origin of the protein-only hypothesis, claiming he originated it a decade after it was actually conjectured. But hey, he was good at getting grants. I was surprised reading a lot of this, because for all the time I’ve been aware of it, the cause of prion disease has seemed settled. “Oh yeah, it’s a protein that gets all fucked up.” But DTM goes through just how unsettled it was right up through to The Family That Couldn’t Sleep’s publication. Serious confirmation only arrived a couple years later. Many people were deeply critical of the prion hypothesis – often, it seemed, because they loathed Prusiner too much to go along. Throughout the book, he cuts an uncharismatic figure. Gajdusek and Prusiner both won the Nobel for discovering prions, decades apart. This tells you something – the “discovery” of prions can be construed quite a few ways. Gajdusek formulated the hypothesis; Prusiner proved it. Gajdusek was grievously offended by Prusiner’s Nobel, perceiving his rival – not inaccurately – as a follower who never originated any ideas of his own. But Gajdusek was offended from a federal prison cell, so how’d that work out for him? Fascinating as all this is, no one published a book about prions in the mid-2000s because it was about kuru or FFI. They published books about prions because teenagers were dying, and people wanted to know why. DTM lays the seeds for part 3 – the mad cow section – in part 1. This is a discussion of scrapie, the longstanding prion disease of sheep. Scrapie was a medical mystery for centuries (remember poor D. R. Wilson), precisely because of the intuitive implausibility of prions. The scrapie chapter is a great history-of-science piece, covering the agricultural productivity revolutions of the 18th century, the surfeit of bizarre origins veterinarians concocted, and the treatments that never worked. Scrapie is not transmissible to humans – well, we hope. It’s concerningly transmissible to primates. But it’s been around for a long, long time, and it doesn’t epidemiologically look like humans get it...we hope. Anyway, you ever tried to generalize from one example? The British government did! In the mid-1980s, strange reports started coming out of the UK’s farms. Farmers were describing a new disease where dairy cows – incredibly docile creatures, under normal circumstances – turned hostile, kicking them as they went into the milking stalls. The symptoms looked to all the world like scrapie. Epidemiologists tracing the outbreaks found a unifying link with “cake” – animal protein feed sweetened with molasses. The scrapie-like symptoms must have traced to an infected sheep. But scrapie doesn’t transmit to humans, so it must be okay to keep slaughtering them, right? We all know how this ended. The best term for the British response to the mad cow outbreak is “cacklingly evil conspiracy”. The agricultural industry really, really didn’t need a huge zoonotic outbreak – so it decided it didn’t have one. They first suppressed all mentions that the disease looked like scrapie, then – when this became impossible – hyped up that scrapie doesn’t transmit to humans, so there’s nothing to worry about. The formal name of the disease, “bovine spongiform encephalopathy”, was supposedly chosen to optimize for unfamiliarity – it wouldn’t fit well in a headline. They emphasized, extensively, that there was nothing to worry about. Ever. At some point, people started asking questions. If there was nothing to worry about, why was the agricultural industry panicking so hard? As things became ever more worry-inducing, this turned down ludicrously twisting paths: Meanwhile, the Southwood Working Party and the experts who advised it were learning on the job. They learned, for instance, that the BSE agent entered the animal through the mouth and then followed the digestive tract into the organs that try to filter out infections—the tonsils, the guts, and the spleen—and from there traveled into the peripheral and central nervous system, and finally arrived at the brain. They also learned that pasties, meat pies, and even some baby foods contained tissues from a lot of those organs. So the Southwood Working Party recommended banning these organs, but only from baby food. This started a chain reaction of consumer doubt: if infected cow organs were unsafe for babies, how could they be good for adults? The government then banned offal, as the organs were collectively called, in all human food but gave the industry a grace period to get it out of the feed supply. Then pet food manufacturers began to wonder if what drove cows mad might not also drive dogs, cats, and parrots mad. The feed they sold came from concentrate made of the same sick animals that had previously made up the meat and bone meal farmers used. Their trade group decided to put a similar ban in place—immediately. So for five months it was safer to be a dog than a human in Britain. DTM spends pretty much this whole section of the book making fun of the British government. To be fair, they deserved it. They killed hundreds of kids in agonizing and preventable ways – they could take some ribbing. This is all throughout the mid-1980s to early-mid 1990s. Through this period, it wasn’t yet clear that mad cow could spread to humans. The panic was clear, and deserved, but it didn’t yet have a match for its powder keg. It would alight. The first suspected case of vCJD – human mad cow – was in 1994. Fifteen-year-old Vicky Rimmer developed a sudden, strange disease. Doctors gave her months to live...until she died in 1998. A couple other suspected cases trickled down through the mid-90s, including a young man who made meat pies for a living, whose grieving mother received a letter from the Prime Minister that “humans do NOT get mad cow disease”. (That must’ve been fun.) Soon, they couldn’t deny it any longer. On March 20, 1996, Stephen Dorrell, the health secretary, stood up in Parliament to announce the news that had already appeared as a tentative conclusion in scientific journals and as rumor in newspapers for the previous two years: British beef was killing British teenagers. The first confirmed death was that of Stephen Churchill, a nineteen-year-old student from Wiltshire, who died in May 1995. Back in 1989, at the Southwood Working Party’s suggestion, the government had set up a surveillance unit in Edinburgh to watch for any evidence that BSE had crossed to humans. One worry had been that if BSE passed to humans, how would anyone know it? How would you recognize something you had never seen? It turned out to be easy: Churchill and the nine other teenagers who had gotten sick had spectacular amyloid plaques in their brains, chunks of dead protein almost visible to the naked eye. If sporadic CJD was a whisper, BSE-caused prion disease was a shout. The investigators sat open-mouthed looking at slides whose damage, they feared, portended the most severe epidemic in modern British history. This part of the book is not fun. It lacks the insane personalities and duelling careers of the other entries. It is an honest chronology of the vCJD epidemic – a gruesome failure of the agricultural industry, the one system that everyone is vulnerable to. The government and industry had completely violated their duty of care to citizens and consumers. They were paying the price. No one would buy British beef anymore – not while they watched their children die. Now here’s the thing: this is ethnography, not historiography. The Family That Couldn’t Sleep is a book from the mid-2000s. The epidemic was not at all in the rear view mirror. There were piles of unanswered questions that DTM constantly alludes to. We have eighteen years more hindsight than he did then. What do we know now? --------------------------------------------------------- In 2006, the vCJD epidemic looked like it was going to be a lot better than the worst fears. BSE itself was a huge problem for the cattle industry, but honestly, no one is too sympathetic to the cattle industry. People were not going to die in anywhere near the numbers believed. We had all sorts of reassuring data coming out about this, which DTM chronicles. We were learning that only some genotypes seemed susceptible to vCJD. We didn’t see any older people die of the disease. We were seeing numbers drop, such that vCJD must have a pretty short incubation period. Anyway, all of this is wrong! The Family That Couldn’t Sleep was written in the candidate gene era. Back then, the nascent field of human genetics was sure it was about to Solve Polygenism. Yes, the simple Mendelian monogenic patterns popular a few decades back clearly didn’t apply to common diseases, but how many variants could there be? We were about to discover the five genes influencing 20% of Alzheimer’s risk each, the five genes influencing 20% of heart disease risk each, etc., and once we were done we’d just do gene therapy and cure Alzheimer’s. A paper on autism genetics from 1999 was so outre as to speculate there might be as many as fifteen genes involved. The fact we are now using the term “omnigenic model” should tell you roughly how well this worked out. Do you remember SNPedia? If you were a 2014 Slate Star Codex reader, you might. 2014 was still pretty candidate gene. People were out there publishing papers saying a single variant could increase your life expectancy by 15 years. SNPedia was a site that beautifully categorized all of these, so you could do 23andme or whatever, look up your results on SNPedia, and make horrible life choices.5 It was eventually bought out by one of the consumer DNA companies, so no one ever edited it again, making it a great time capsule of early-mid 2010s behavioural/medical genetics takes. SNPedia will excitedly explain to you that common genetic variants make you immune to vCJD. They cite a 2009 post from the now-archived 23andme blog titled “No Good Evidence That Potential Pool of Mad Cow Disease Victims Is Expanding”, explaining how fears of late-onset vCJD are clearly debunked by new Scientific Knowledge. Everyone who developed vCJD in the 1990s and 2000s had an M/M genotype in a particular part of the PRNP prion gene, so the roughly half the population with M/V or V/V genotypes were immune. The Family That Couldn’t Sleep buys this, too. In fact, it buys it in an even more agonizingly 2000s way. The first sign that transmissible prion diseases weren’t genotype-restricted should’ve been the growth hormone kids. You might have heard this story – from the late 1950s through mid-1980s, human growth hormone produced from brain tissue was used as a treatment for pituitary dwarfism, until it turned out to spread CJD if the originating brain was infected. DTM discusses this, to set the scene for the genetics thing. He mentions what was the state of the art at the time – that a disproportionate share of both the growth hormone kids and sporadic CJD cases were V/V homozygotes. This, uh – so the book was written in the mid-2000s, yeah? Yeah. The conclusion DTM drew – and this was a common conclusion at the time – was that homozygosity somehow made you more vulnerable to CJD, and M/M homozygosity made you vulnerable to BSE-borne CJD in particular. We cannot criticise the author for not predicting the future, but we live in the future, and can say how this worked out. Turns out, nope, M/V heterozygotes totally get vCJD. After a British man in his 30s died of CJD in 2016, he was found to have vCJD and an M/V genotype. He was tested for vCJD only because he was exceptionally young for someone with a sporadic prion disease – meaning people developing it later in life would be missed6. Did you know up to 1 in 2000 people in the UK have latent vCJD? There is one line in The Family That Couldn’t Sleep that stopped me dead in my tracks when I read it: What happens to the Italian family in the end depends less on their own actions than on the world’s interest in prion diseases, which they cannot control. If lots of people are afraid of getting variant CJD, the family benefits. If fear of prion disease goes the way of the fear of swine flu or Ebola, then they will be orphaned again. THIS BOOK IS FROM 2006! Three years before the swine flu pandemic! Eight years before the Ebola pandemic! “If you’re looking for a sign, this is it.” --------------------------------------------------------- The last section of The Family That Couldn’t Sleep addresses BSE fears in America and a nascent internet subculture DTM calls “Creutzfeldt Jakobins” – people who track American CJD cases, trying to spot vCJD patterns. When reading his description of the Creutzfeldt Jakobins, my mind constantly, uncontrollably turned to covid. Here it was – an online community of people deeply skeptical about a disease’s official story, tracking every contradiction, every implausibility, every statistic that failed to apply to the individual. Self-described “redneck hippies” and “soccer mom Republicans” teaming up to find the truth hidden behind an impossible world. You know what they’re doing now. I’ve always combined a deep interest in medicine with a healthy distrust for it. People who are constitutionally inquisitive, anti-authoritarian, and suspicious about official narratives tend to end up skeptical of at least some mainstream claims in the field. This is not to say I think you should take bleach enemas or something, just that I understand the impulse behind concluding the US government was covering up a local vCJD wave. Traditionally, sporadic prion diseases are said to have a prevalence of one in a million. (Hold on to that for a second.) The last section of the book is a chronology of Americans finding bizarrely more than one in a million of their friends dying of sporadic CJD, often at inexplicably young ages, sometimes in geographical clusters. This is understandably suspicious. Then DTM goes on to reassure us by saying none of these cases were confirmed to have an M/M genotype, which OH GOD OH FUCK A number of high-profile people in the prion world, including Gajdusek, are clarified as not believing sporadic prion diseases exist. You get the impression DTM doesn’t, either. Now, how common are prion diseases? Eric Vallabh Minikel has an answer for you! Eric and his wife Sonia are prion researchers from a rather unique background – after Sonia was diagnosed as having a single-gene mutation with ~100% penetrance for prion disease, they left their previous jobs to dedicate their lives to curing it. It turns out, when you run the numbers, you get not one in a million but 1 in 5000 people dying of prion diseases. This is best described as “nightmarishly high”. I’m normed on genetic disorders. A genetic disorder that affects one in five thousand people is pretty common! I have known, in person, completely unselected, just from “random people I’ve met in my life in a non-medical context”, someone with a ~1/250k syndrome and someone with a ~1/50k-100k syndrome. I don’t think anyone in my extended family knows someone who died of a prion disease. I feel like it would’ve come up if they did! Prion diseases have distinctive phenotypes. Not distinctive enough, apparently, to avoid a lot of CJD being misdiagnosed as Alzheimer’s – but diagnosis is consistently insane. Something DTM reiterates throughout The Family That Couldn’t Sleep is just what prion dementia looks like. The characteristic dementia in prion diseases spares something – “self” or “recognition” or “reflection” – that is not spared by Alzheimer’s, or by most common dementias. Shouldn’t this be, uh, noticeable?7 They kill rapidly, often over the course of months, and often onset in midlife. ALS shares this pattern and is way, way more common than prion diseases; you hear about ALS far more in the “disorder people actually have” sense. What am I missing here? Anyway: 1 in 2000 prevalence of latent vCJD in the UK + extreme lack of clarity over whether scrapie is human-transmissible + blood donations spread vCJD + sporadic CJD prevalence keeps going up = ??? (Yes, I am annoyed that most countries have lifted their ban on UK blood donors, thank you for asking!) --------------------------------------------------------- But back to the book. The “American chapter” is one-third about the country’s response to vCJD, one-third about the Creutzfeldt Jakobins, and one-third about chronic wasting disease. The last part is the most interesting. Chronic wasting disease is a prion disease of deer. Like scrapie, it “probably, we hope” isn’t human-transmissible (eat venison at your own risk). Under natural circumstances, deer shouldn’t get prion diseases: A prion plague should not be possible among ruminants in the wild. Deer are not cannibals, as the cows that spread BSE were forced to be; and, because deer and elk are not domesticated, they do not have enough contact with one another to spread a prion infection the way sheep are thought to spread scrapie. But deer do not live as they used to live, humans having once again brought their ambitions to bear on the natural course of things. The Family That Couldn’t Sleep is a book of medical anthropology. Anthropology of the Veneto, anthropology of Papua New Guinea, anthropology of 1990s Britain. Here, it is an anthropology of America. Americans, having won the world, still fight to win their own backyard. The North American continent is geographically diverse, cutting through rain-snow-shine, mountains jutting over plains, cities sprawling into wilderness, habitations criss-cross dotted with surprisingly few empty zones. Go somewhere like Denver, the Mile High City, three million people fighting against nature. Few other countries have anything like this; geographically vast polities usually have uninhabitable blocks. Australians are twenty-five million people clustered against the shore. It still surprises me, after all this time, how every US state has a meaningful city8. Midcentury Denver, growing and sprawling out across its mountains, started to run into their natural inhabitants – deer. Starvation is one way nature adjusts the deer population to the available food supply. People did not usually see this process, but in the 1950s and 1960s Colorado became more densely settled, reducing forested areas and forcing deer to look longer and harder for food. At the same time, the state enacted conservation laws, limiting when and where hunters could shoot. Soon emaciated deer began wandering onto the lawns and through suburban streets looking for a meal. People began to feed them, only to find that they died anyway. They would drop dead by haystacks, along highways, and in flower beds. In the late 1960s, a young biologist named Gene Schoonveld tried to figure out why the deer starved even when they were fed.9 He deprived some deer of food for a while, “[h]e cut windows in their stomachs to see what went on inside, and then he began to feed them”. While this was going on, he had a control group of healthy, well-fed deer as backups in case anything went wrong. It did...but not to the experimental group. The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie? They didn’t eat the sheep, presumably. Did it somehow transmit from casual contact? This is not supposed to happen. And yet: the deer in the sheep pen started dying of a mysterious scrapie-like disease, one never reported before, that would go on to infect thousands. These deer were released into the wild. Ten years later, the first reports of chronic wasting disease came out. The disease spread across deer and elk in the western half of the country. By the turn of the millennium, cases were exploding – and lost all geographical restriction. DTM can report up to 2005, at which point it was floating around Upstate New York. This kind of spread doesn’t track natural deer migration. That’s irrelevant, because nothing about CWD’s spread is natural. We shift gears into an anthropology of the American hunter. The hunter wants to shoot the most impressive buck, to bag himself one with as many “points” as possible – one whose antlers branch out most. A “ten-point buck” has five branches on each horn: Original by Ric McArthur Nature doesn’t make enough bucks with perfectly symmetrical ten-point horns. To fill the demand, the market had to step in. Thus was born the deer farm industry, which raises captive deer in better genetic and nutritional conditions than Nature permits, then ships them across the country so hunters who couldn’t get legit ten-point bucks get the taxidermy piece for their wall. These are controversial amongst hunters and illegal in numerous states – but the industry is big enough to spread CWD. (The kind of hunter who needs a deer shipped to his house is the kind of hunter who will fumble killing it.) Another problem is supplemental feeding – leaving out protein-enriched food for deer to eat. This produces “trophy class animals at an earlier age”, but again, what’s in that protein? (“It is much like feeding your cows 41 percent protein cottonseed cake during the winter to raise the protein level in the cow’s diet to a level that will maintain acceptable production”, says that article from 1991.)10 The book segues into a vignette. CWD was new in Wisconsin in the early 2000s, and the state’s Department of Natural Resources was optimistic it could eradicate it. In a state with a love of hunting, you could, in theory, recruit people to kill every single deer in a 400-square-mile radius: In many states, the state would have had to call out the National Guard for such an onslaught, but hunting is a passion in Wisconsin. Hunters shoot 450,000 deer every year, more than in any other state. “I’m looking for ardent hunters to help us, unless fear or their wives keep them away,” one DNR official told a Milwaukee magazine. The state extended the normal hunting season and waived the usual limit of one buck per hunter, and the hunters came out in force. The whole affair was gruesome – one official called it “hunting for slob hunters”. If you’re trying to eradicate a prion disease, you can’t very well let people take the carcasses home to eat. Bodies piled up in control stations, decomposition mingling with bleach. The 2002 hunt established a base rate of 2% for chronic wasting disease in Wisconsin deer, with the most affected areas getting up to 10%. Further hunts in 2003, 2004, and 2005 spread to wider and wider areas – and didn’t move the needle one bit. This is to say that CWD is quite a bit more common in the American deer population than BSE ever was in British cattle. Since publication, it’s popped up in Norway and South Korea. Notably, Norway doesn’t allow for the import of cervids, raising numerous questions about how it got there. There are no unambiguous cases of CWD transmission to humans, and in vivo/in vitro primate studies have mixed results. There sure are some unusually young hunters with sporadic CJD, though. But don’t worry, most of them aren’t M/M homozygotes! There is an absolute ton going on in this book. I’ve had to skim over whole sections. Parts that couldn’t be easily slotted into a narrative review include: When Gajdusek was invited to a party at Prusiner’s house, he was horrified to find his rival had purchased hundreds of New Guinean statues – all with the genitals removed.
SLS

SLS is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "SLS sends an Orion around the moon". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
SLS
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
1. Widely accepted paper claims a polygenic score predicting over 25% of human intelligence: 70% 2. …50% or more: 20% 3. At least one person is known to have had a “designer baby” genetically edited for something other than preventing specific high-risk disease: 10% 4. At least a thousand people have had such babies, and it’s well known where people can go to do it: 5% 5. At least one cloned human baby, survives beyond one day after birth: 10% 6. Average person can check their polygenic IQ score for reasonable fee (doesn’t have to be very good) in 2023: 80% 7. At least one directly glutamatergic antidepressant approved by FDA: 20% 8. At least one directly neurotrophic antidepressant approved by FDA: 20% 9. At least one genuinely novel antipsychotic approved by FDA: 30% 10. MDMA approved for therapeutic use by FDA: 50% 11. Psilocybin approved for general therapeutic use in at least one country: 30% 12. Gary Taubes’ insulin resistance theory of nutrition has significantly more scholarly acceptance than today: 10% 13. Paleo diet is generally considered and recommended by doctors as best weight-loss diet for average person: 30% 14. SpaceX has launched BFR to orbit: 50% 15. SpaceX has launched a man around the moon: 50% 16. SLS sends an Orion around the moon: 30% 17. Someone has landed a man on the moon: 1% 18. SpaceX has landed (not crashed) an object on Mars: 5% 19. At least one frequently-inhabited private space station in orbit: 30%
smartphone

smartphone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 06, 2024 and August 06, 2024. The archive places it in contexts such as "and produced... the smartphone". It most often appears alongside AI, altruism, America.

Reference entry
smartphone
Mention count
1
Issue count
1
First seen
August 06, 2024
Last seen
August 06, 2024
August 06, 2024 · Original source
I’m skeptical of this argument. America’s been at peace since World War II (foreign adventures like Vietnam haven’t substantially changed our national experience) and produced the computing revolution, the Internet, AI, the moon landing, the Human Genome Project, antiretrovirals, the microwave, the laser, the smartphone, and the reusable rocket. During that time, Iraq has had approximately eight major wars and didn’t even get a cuckoo clock out of it.
SmartSave card

SmartSave card is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 07, 2022 and December 07, 2022. The archive places it in contexts such as "We now have the SmartSave card, a great source for all prescription drug savings". It most often appears alongside Blue Helmet, Blue Helmet Insurance, Chakaramanditya.

Reference entry
SmartSave card
Mention count
1
Issue count
1
First seen
December 07, 2022
Last seen
December 07, 2022
December 07, 2022 · Original source
"Hello! This is SmartSave pharmacy, home of compassionate savings on drugs, vitamins, and more. Our hours are from 9 AM to 5 PM Mondays through Fridays, 10 AM to 4 PM Saturdays, 10 AM to 3 PM Sundays, 10 AM to 3:30 PM on Christmas, Christmas Eve, Thanksgiving, and New Years, and 9:30 AM to 4:30 PM on Easter, Memorial Day, and Tu B'Shevat. We now have the COVID booster at SmartSave pharmacy! Did you know that COVID boosters can protect against all variants of COVID? Schedule your COVID booster now! We also have the SmartSave card, a great source for all prescription drug savings. ¡Hola! Esta es la farmacia SmartSave, hogar de ahorros compasivos en medicamentos, vitaminas y más. Nuestro horario es de 9 a. m. a 5 p. m. de lunes a viernes, de 10 a. m. a 4 p. m. los sábados, de 10 a. m. a 3 p. m. los domingos, de 10 a. :30 p. m. en Semana Santa, Día de los Caídos y Tu B'Shevat. ¡Ya tenemos el refuerzo COVID en farmacia SmartSave! ¿Sabía que los refuerzos de COVID pueden proteger contra todas las variantes de COVID? ¡Programe su refuerzo COVID ahora! Tambien tenemos la tarjeta SmartSave, una gran fuente para todos los ahorros en medicamentos recetados. If you would like to hear this introductory message again, press 1. Otherwise, stay on the line."
"Hello! This is SmartSave pharmacy, home of compassionate savings on drugs, vitamins, and more. Our hours are from 9 AM to 5 PM Mondays through Fridays, 10 AM to 4 PM Saturdays, 10 AM to 3 PM Sundays, 10 AM to 3:30 PM on Christmas, Thanksgiving, and New Years, and 9:30 AM to 4:30 PM on Easter, Memorial Day, and Tu B'Shevat. We now have the COVID booster at SmartSave pharmacy! Did you know that COVID boosters can protect against all variants of COVID? Schedule your COVID booster now! We now have the SmartSave card, a great source for all prescription drug savings. ¡Hola! Esta es la farmacia SmartSave, hogar de ahorros compasivos en medicamentos, vitaminas y más. Nuestro horario es de 9 a. m. a 5 p. m. de lunes a viernes, de 10 a. m. a 4 p. m. los sábados, de 10 a. m. a 3 p. m. los domingos, de 10 a. :30 p. m. en Semana Santa, Día de los Caídos y Tu B'Shevat. ¡Ya tenemos el refuerzo COVID en farmacia SmartSave! ¿Sabía que los refuerzos de COVID pueden proteger contra todas las variantes de COVID? ¡Programe su refuerzo COVID ahora! Ahora tenemos la tarjeta SmartSave, una gran fuente para todos los ahorros en medicamentos recetados. If you would like to hear this introductory message again, press 1. Otherwise, stay on the line."
Smithfield

Smithfield is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2024 and June 28, 2024. The archive places it in contexts such as "a group of activists broke into a Smithfield pork farm". It most often appears alongside 2023 special, ACX grant winners, African Gray Parrot.

Reference entry
Smithfield
Mention count
1
Issue count
1
First seen
June 28, 2024
Last seen
June 28, 2024
June 28, 2024 · Original source
Scully goes to a hog farm in North Carolina owned by one of the world’s largest pork producers, Smithfield Foods, to see for himself what we lose when we treat animals like literal production machines. He uses his conservative credentials to slide under their radar. He’s given a full tour of the farm, access that other animal activists can only achieve by breaking in under cover of night.
After his visit, Scully sits down for an interview with a corporate executive from Smithfield and self-described conservative, Jerry Godwin. The reader is left to wonder whether Scully finds it amusing that this ultimate bad guy boss, this affront to all he holds dear, has the last name “God win.”
When Scully reflects on all that he’s witnessed, he is dismayed at the bastardization of conservatism that can justify what he saw at the Safari Club convention and on the Smithfield pork farm:
Snapchat

Snapchat is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 29, 2022 and September 29, 2022. The archive places it in contexts such as "hand out flyers advertising Snapchat". It most often appears alongside 1 Kings 10-11, 2008 Democratic National Convention, Adam Scheffer.

Reference entry
Snapchat
Mention count
1
Issue count
1
First seen
September 29, 2022
Last seen
September 29, 2022
September 29, 2022 · Original source
Evan was willing to try anything to get users. When he was home in Pacific Palisades, he would go to the shopping mall and hand out flyers advertising Snapchat. “I would walk up to people and say, ‘Hey would you like to send a disappearing picture?’ and they would say, ‘No,’” Evan later recalled.
— How to Turn Down a Billion Dollars, The Snapchat Story by Billy Gallagher
Snoo

Snoo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 22, 2023 and December 22, 2023. The archive places it in contexts such as "The Snoo is a $1500 computerized bassinet that continually assesses babies’ needs". It most often appears alongside ACX, Alexey Guzey, America.

Reference entry
Snoo
Mention count
1
Issue count
1
First seen
December 22, 2023
Last seen
December 22, 2023
December 22, 2023 · Original source
The Snoo is a $1500 computerized bassinet that continually assesses babies’ needs and tries to calm them with various soothing noises and automated rocking motions. We got two, both of which have been soundly rejected. The twins insist on sleeping in their carseats, which we’ve grudgingly moved to the nursery. At first I was miffed, but now I see their logic. You’ve got to learn to resist the algorithmic content mills early.
Solana wallet

Solana wallet is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2022 and August 16, 2022. The archive places it in contexts such as "And you need to have a Solana wallet, own crypto, and know how to use it". It most often appears alongside 538, 538, @tnim_.

Reference entry
Solana wallet
Mention count
1
Issue count
1
First seen
August 16, 2022
Last seen
August 16, 2022
  • 22 August 16, 2022
August 16, 2022 · Original source
What’s the catch? Offer not open to US citizens - a vexing, problematic negation. And you need to have a Solana wallet, own crypto, and know how to use it. And there’s not a lot of volume so far. But otherwise, no catch. This is just a really good new thing. Think of it as Manifold Markets, but with real money (and 10x harder to use).
solanezumab

solanezumab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "earlier antibodies that saw only failure in phase 3 – solanezumab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
solanezumab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
Donanemab in phase 2 [81] (32%) and phase 3 [82] (35%). There have also been earlier antibodies that saw only failure in phase 3 – bapineuzumab [83, 84], crenezumab [85], solanezumab [86–88], and gantenerumab [88, 89]. These failed drugs didn’t just do a bad job treating Alzheimer’s. They also did a bad job clearing amyloid plaques, so their failure is consistent with the amyloid hypothesis. That said, just coupling the older, previously-unsuccessful antibody gantenerumab with a BBB-crossing mechanism produced extremely good target engagement and better safety in early clinical trials [74–76]. This makes me optimistic about a future BBB-crossing lecanemab (or similar), especially if given in the preclinical disease phase prior to significant tauopathy. Each of the “successes” have shown about 25-30% slowing of decline over 18 months. Some object that this isn’t clinically meaningful because it’s only a slowdown of ∼0.5 points on an 18-point CDR-SB scale, but they don’t mention that the participants start about 3 points from a perfect score (since these are relatively early-stage patients) and worsen by ∼1.5 points in those 18 months when on placebo. A literally perfect drug - one which halted all further clinical progression - could therefore only achieve about 1.5 points of efficacy on that scale. The cruxy question is whether the drugs maintain a 30% reduction after 18 months. Preliminary signs from lecanemab’s and donanemab’s open-label extensions show that they do [90], so this would amount to about 40% more years of life at each disease stage. But why have amyloid antibodies only achieved about 30% efficacy so far? The likely answer: mainly because they were given too late to prevent the downstream tau pathology cascade, but also because some of their side effects, like when they target amyloid-bearing blood vessels rather than brain tissue, can themselves worsen cognition. That said, even achieving 30% efficacy proves that amyloid plays some causal disease role and isn’t merely a downstream, harmless pathology. Why is the amyloid hypothesis unpopular? The amyloid hypothesis remains popular in the Alzheimer’s disease research community, but most press coverage is negative. These challenges are understandable, and some of them make good points, but overall fail to address the evidence discussed above. Failures and perceived failures of amyloid therapies I discussed this above, but to recap: Early attempts had suboptimal epitopes which didn’t successfully engage their targets.
[86] R. S. Doody et al., “Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease,” New England Journal of Medicine, vol. 370, no. 4, pp. 311–321, 2014, doi: 10.1056/NEJMoa1312889.
[87] L. S. Honig et al., “Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease,” New England Journal of Medicine, vol. 378, no. 4, pp. 321–330, Jan. 2018, doi: 10.1056/NEJMoa1705971.
sotrovimab

sotrovimab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 23, 2021 and November 23, 2021. The archive places it in contexts such as "including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid". It most often appears alongside 1/6 insurrectionists, Ahmed, Alabama.

Reference entry
sotrovimab
Mention count
1
Issue count
1
First seen
November 23, 2021
Last seen
November 23, 2021
November 23, 2021 · Original source
Author appears to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid.
The steps required to accept the no-significant-effect outcome are extreme — one needs to find a reason to exclude most of the studies, disregard the strong treatment-delay response relationship, and disregard all prophylaxis studies. Even after this, the result is still positive, just not statistically signficant. This does not support a negative recommendation. Widely accepted and effective (subject to dependence on viral variants) treatments like casirivimab/imdevimab, bamlanivimab, and sotrovimab were all approved without statistically significant mortality benefits.
First, the claim that I "[appear] to be against all treatments, labeling them all "unorthodox" and "controversial", even those approved by western health authorities, including casirivimab/imdevimab, bamlanivimab, sotrovimab, and paxlovid." They suggest I am turning my readers away from other treatments including ones that are already standard of care in western health systems.
Soylent

Soylent is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 16, 2026 and January 16, 2026. The archive places it in contexts such as "a frustrated groping towards meal replacements like Soylent or Huel". It most often appears alongside Adams, Alice, All-Seeing Eye.

Reference entry
Soylent
Mention count
1
Issue count
1
First seen
January 16, 2026
Last seen
January 16, 2026
January 16, 2026 · Original source
Okay, “I am cleverer than everyone else”, got it. His next venture (c. 1999) was the Dilberito, an attempt to revolutionize food via a Dilbert-themed burrito with the full Recommended Daily Allowance of twenty-three vitamins. I swear I am not making this up. A contemporaneous NYT review said it “could have been designed only by a food technologist or by someone who eats lunch without much thought to taste”. The Onion, in its twenty year retrospective for the doomed comestible, called it a frustrated groping towards meal replacements like Soylent or Huel, long before the existence of a culture nerdy enough to support them. Adams himself, looking back from several years’ distance, was even more scathing: “the mineral fortification was hard to disguise, and because of the veggie and legume content, three bites of the Dilberito made you fart so hard your intestines formed a tail.”
SpaceX

SpaceX is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "He wings most of the announcements from Tesla and SpaceX". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
SpaceX
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
Musk creates cognitive dissonance: how can someone be so smart and so dumb at the same time? To reduce the dissonance, people have spawned a whole industry of Musk-bashing, trying to explain away each of his accomplishments: Peter Thiel gets all the credit for PayPal, Martin Eberhard gets all the credit for Tesla, NASA cash keeps SpaceX afloat, something something blood emeralds. Others try to come up with reasons he’s wholly smart - a 4D chessmaster whose apparent drunken stumbles lead inexorably to victory.
Elon Musk: Tesla, SpaceX, And The Quest For A Fantastic Future delights in its refusal to resolve the dissonance. Musk has always been exactly the same person he is now, and exactly what he looks like. He is without deception, without subtlety, without unexpected depths.
His employees seem to think so. Here’s a quote from former SpaceX employee Kevin Watson:
Spartacus

Spartacus is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 27, 2024 and May 27, 2024. The archive places it in contexts such as "ACX grantee Spartacus is an app for assurance contracts". It most often appears alongside Astralcodexten, DaystarEld, Jordan Braunstein.

Reference entry
Spartacus
Mention count
1
Issue count
1
First seen
May 27, 2024
Last seen
May 27, 2024
May 27, 2024 · Original source
1: ACX grantee Spartacus is an app for assurance contracts, ie solving collective action problems, ie Kickstarter for everything. If you would go to a protest march if and only if there are 10,000 other people there, you can mark your interest on the app and get notified if it reaches its goal. The team wants to announce that they'll be unveiling their MVP during NYC TechWeek at the event listed here; anyone in the area is welcome to attend. Project lead Jordan Braunstein will be in NYC from 5/29 to 6/15 and is interested in meeting anyone interested in "collaboration, partnerships, use cases, red teaming, and additional funding sources". Email him at jordan@spartacus.app.
Splitwise

Splitwise is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 20, 2022 and December 20, 2022. The archive places it in contexts such as "You know how Splitwise facilitates splitting an arbitrary bill with your friends?". It most often appears alongside 7-11, AGI, AMC.

Reference entry
Splitwise
Mention count
1
Issue count
1
First seen
December 20, 2022
Last seen
December 20, 2022
December 20, 2022 · Original source
- You know how Splitwise facilitates splitting an arbitrary bill with your friends? Something like that, but to facilitate making a simple prediction market in a small group, and leaving it to you guys to "pay out" in money or whatever. Manifold is not very technologically suitable for this and it probably won't be soon.
Spravato

Spravato is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 19, 2021 and July 19, 2021. The archive places it in contexts such as "you can use Spravato. Spravato is an FDA-approved official ketamine spray". It most often appears alongside Adderall, alcohol, AMPA receptors.

Reference entry
Spravato
Mention count
1
Issue count
1
First seen
July 19, 2021
Last seen
July 19, 2021
July 19, 2021 · Original source
Second, you can use Spravato. Spravato is an FDA-approved official ketamine spray. You won’t have get anything injected into your veins, and it’s a less “medical”-feeling experience than a clinic. But this has its own problems. Spravato isn’t exactly ketamine – it’s esketamine, a ketamine component, which might or might not work as well as regular ketamine. It’s only allowed in doses of 56 to 84 mg, which will be too low for many people. And it also costs about $6400/month and has to be administered in special clinics. The only saving grace is that some people’s insurances will cover this one after a lot of begging. I still don’t think it’s the best option for most people.
The standard dose of intranasal ketamine is 50 – 80 mg. This is more or less the dose recommended by UpToDate, the dose used in most studies, the FDA-recommended dose of Spravato, and the dose that most successful ketamine providers have told me they use.
Square

Square is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 29, 2024 and August 29, 2024. The archive places it in contexts such as "I'll send a simple Square $0 ticket link". It most often appears alongside 10 N Park Pl, 12th Ave South, 1525 Bank St.

Reference entry
Square
Mention count
1
Issue count
1
First seen
August 29, 2024
Last seen
August 29, 2024
August 29, 2024 · Original source
Contact: Steven Contact Info: steven[dot]shonts[a t]gmail[d ot]com Time: Sunday, September 01st, 03:00 PM Location: Too Fast To Sleep (Siam) สยาม - 222,222/1-7,224 ซอย Siam Square Soi 1, Pathum Wan, Bangkok 10330 Coordinates: https://plus.codes/7P52PGVJ+XJ
Contact: Steve Contact Info: Steve[dot]Bachelor[a t]gmail[d ot]com Time: Sunday, September 08th, 04:00 PM Location: The Starbucks at Mailaender Platz, 70173 Stuttgart - Up the stairs from the Budapester Platz or Stadtbibliothek U-train stops to the open square area of the Milaneo mall. Coordinates: https://plus.codes/8FWFQ5RM+97 Notes: I don’t actually speak any German; I just got here.
Contact: Satya Benson Contact Info: acx[dot]meetup[at]satchlj[dot]com Time: Saturday, October 12th, 03:00 PM Location: George Square Gardens Labyrinth Coordinates: https://plus.codes/9C7RWRV6+G5 Notes: If it rains, the backup location is Söderberg The Meadows (https://plus.codes/9C7RWRV5+C7)
SSRIs

SSRIs is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 24, 2022 and November 24, 2022. The archive places it in contexts such as "with depression and SSRIs". It most often appears alongside ACE inhibitors, ACE inhibitors, Adderall.

Reference entry
SSRIs
Mention count
1
Issue count
1
First seen
November 24, 2022
Last seen
November 24, 2022
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
St. John’s Wort

St. John’s Wort is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful"; "Zembrin probably works better than ... St. John’s Wort"; "Zembrin probably works better than 5-HTP or St. John’s Wort". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
St. John’s Wort
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
The most-studied and best-supported supplements for depression is l-methylfolate. Tryptophan/5-HTP, SAM-e, fish oil and St. John’s Wort may also be helpful. Less-well-studed but promising supplements including Zembrin and polygala tenuifolia. I am currently avoiding discussion of tianeptine, a foreign antidepressant which is sometimes sold as a supplement in the US, until I figure out the legal gray areas around it, but you might consider looking into it on your own. Going through the others one by one:
St. John’s Wort is a plant which has been used in herbal medicine for centuries (its name may come from the Knights of St. John, who used it to treat wounds while crusading). The most important active chemical, hyperforin, might be a weak reuptake inhibitor of various chemicals, including serotonin (which would technically make it an SSRI), but as far as I can tell this is too weak to really explain its effects. A meta-analysis of 35 studies including 6993 patients suggests it works, but other studies show no benefit. German studies tend to do the best and American studies the worst, which might either reveal something about those countries’ cultural biases, or about the different strains and extracts of the plant used in the two countries. This herb is infamous for interacting with various medications, and if you’re taking anything else you should talk to your doctor before starting it. This seems like a reasonable brand, but I’m open to suggestions for better ones.
Regimen 1B: Person with no access to a doctor, low time/energy budget: Take 5-HTP 100 mg, increase after one week to 200 mg, increase after three weeks to 300 mg. If that doesn’t work, stop 5-HTP, wait one week, start St. John’s Wort, 900 mg daily, for one month. If that doesn’t work, you may need to either get a doctor or increase the time/energy budget you’re willing to commit.
Stability.ai StableDiffusion

Stability.ai StableDiffusion is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 12, 2022 and September 12, 2022. The archive places it in contexts such as "Stability.ai StableDiffusion announced August 2022". It most often appears alongside DALL-E2, Gary Marcus, Google.

Mention count
1
Issue count
1
First seen
September 12, 2022
Last seen
September 12, 2022
September 12, 2022 · Original source
Stability.ai StableDiffusion announced August 2022.
StableDiffusion: 0/5
Steam

Steam is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 22, 2022 and September 22, 2022. The archive places it in contexts such as "Steam wasn't "first", they were just the first to establish a tight market niche". It most often appears alongside Adam Neumann, Alex Roesch, Amazon.

Reference entry
Steam
Mention count
1
Issue count
1
First seen
September 22, 2022
Last seen
September 22, 2022
September 22, 2022 · Original source
Maybe taking Amazon off the table clarifies things a bit. How about digital distribution of Video Games? This seems like a thing that wasn't invented by anyone in particular, and Steam wasn't "first", they were just the first to establish a tight market niche.
I got so tired of people pitching their Steam competitor startups to me I wrote a blog post about all the reasons they were going to utterly fail:
https://www.fortressofdoors.com/so-you-want-to-compete-with-steam/
Stinger missiles

Stinger missiles is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "the CIA secretly gives Stinger missiles". It most often appears alongside Achilles, Afghan, America.

Reference entry
Stinger missiles
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
The Pax Americana playbook for international norm violations is: the US slaps sanctions on the offender. The EU expresses “concern”. The UN proposes a resolution condemning it, which gets vetoed by whichever Security Council member is most complicit. And the CIA secretly gives Stinger missiles to everyone involved.
Story Living By Disney

Story Living By Disney is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 28, 2022 and June 28, 2022. The archive places it in contexts such as "creating planned communities ... Story Living By Disney". It most often appears alongside Achille Mbembe, Africa Next 50 Cities Coalition, African DAO.

Reference entry
Story Living By Disney
Mention count
1
Issue count
1
First seen
June 28, 2022
Last seen
June 28, 2022
  • 22 June 28, 2022
June 28, 2022 · Original source
Shorts 1: I previously mentioned the scam/fiasco/insane-idea of Hammer City, a planned black nationalist city in the Rocky Mountains. I knew it had failed, but I didn’t know exactly how. Now Colorado Sun has investigated. The proximal reason it failed was because the black nationalists started moving their paramilitary onto the land before they had officially bought it, the owner called the cops, and the cops removed them. The Hammer City team has not given back any of the $112,000 which they raised from extremely credulous donors (without using NFTs, even!) 2: The Charter Cities Institute continues doing the long-term ground-level work necessary to create long-term well-grounded charter cities which will be much too boring and responsible for me to write silly profiles of. Some of their most recent work has been with the Africa Next 50 Cities Coalition, which “convenes and mobilizes key stakeholders who are dedicated to harnessing Africa’s rapid urbanization for human prosperity”. 3: Also, CCI founder Mark Lutter has left the organization to start a charter city of his own, no public details yet. CCI will be looking for a new executive director. 4: Speaking of Disney, they’ve been building on their model city expertise and magical storybook branding by creating planned communities around the US - Story Living By Disney, starting with Rancho Mirage California. Realistically it just looks like a very nice planned community, but this planned community comes with the option to have people make fun of you forever for living in a Disney community as an adult. Predictions for this month: Prospera is still substantially a functioning ZEDE in 2025: 70%
Strattera

Strattera is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 25, 2021 and January 25, 2021. The archive places it in contexts such as "My doc had me on Strattera at first, didn't help at all". It most often appears alongside Adderall, ADHD, AHS.

Reference entry
Strattera
Mention count
1
Issue count
1
First seen
January 25, 2021
Last seen
January 25, 2021
January 25, 2021 · Original source
How is this not more widely prescribed? My doc had me on Strattera at first, didn't help at all. Next I switched to Concerta, which worked, but increased my anxiety, and I had a crash. Next I switched to Adderall, which had almost the same effect as Concerta but on top of that I had no appetite. Finally I switched to Desoxyn and that's when my life started to turn around. My grades instantly went up and homework became fun for me. Math problems became like a puzzle, and history became fun, like watching a real-life movie. Right when I made the switch to Desoxyn, I got caught up on ALL my homework and my grades instantly switched from D's and F's to B's and A's. Not only that, but my social anxiety was completely GONE.
Super Mario Brothers

Super Mario Brothers is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 16, 2022 and November 16, 2022. The archive places it in contexts such as "a fat dude wearing a Super Mario Brothers T-shirt at Home Depot". It most often appears alongside @AutismCapital, Adderall, ADHD.

Reference entry
Super Mario Brothers
Mention count
1
Issue count
1
First seen
November 16, 2022
Last seen
November 16, 2022
November 16, 2022 · Original source
The reason cryptocurrency has changed the world, and will continue changing the world, is not because a fucking Shiba inu coin went 10,000%X because a narcissistic man-baby tweeted about it. It's because decentralized sound money has value. I've seen crypto build up from literally nothing. Even buying bitcoin was next to impossible back then. I mined BTC with my laptop at first. I stopped because I "only" mined 5 BTC per night, and it was using too much power. My first BTC I ever bought was when I met a fat dude wearing a Super Mario Brothers T-shirt at Home Depot. We met in the garden section and sat on a bench to talk about how bitcoin worked, how it was going to change the world, and how to transfer between wallets. I still have the wallet I setup and used to buy that BTC from him. Through all the craziness that has happened in the crypto space over the past 12 years, I have always been able to access my private wallets. Store your crypto in your own cold storage wallet unless you are actively trading. The moment you "lend" your coins out to someone for yields, it's already as good as gone. You've missed the entire point that Satoshi tried to get across so many years ago. Not your keys, not your coins. If you lost money in this shitshow, don't worry. This will all pass, and we will all be stronger for it. Just learn from it all and move on. Buy BTC and ETH, hold it in your cold storage wallets, and wait for the next bull cycle. Watch out for thieves and frauds trying to convince you into "the next big coin." They are all liars and thieves. Real cryptocurrency will endure. For it to really flourish, the shitcoin casinos must die. If you buy some new fucking Frodo Baggins faced shitcoin in the future and lose it all, you only have yourself to blame.
Supermemo

Supermemo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 20, 2021 and May 20, 2021. The archive places it in contexts such as "experiments with Anki / Supermemo style SRS flashcards". It most often appears alongside 5D Chess With Multiverse Time Travel, AI X-Risk Research Podcast, Alignment Research Center.

Reference entry
Supermemo
Mention count
1
Issue count
1
First seen
May 20, 2021
Last seen
May 20, 2021
May 20, 2021 · Original source
3: Best of Less Wrong: Seven Years Of Spaced Repetition Software In The Classroom. Describes a teacher’s experiments with Anki / Supermemo style SRS flashcards; the conclusion is that using them is complicated, they sort of work, but they helped him realize how much of learning isn’t about memorizing things. I appreciated this most for its theory that it’s important to make kids learn specific facts, but not so important that they remember them; teaching someone (eg) Civil War history is “training” a “predictive model” of the Civil War, war in general, and history in general which will survive and remain useful even after the specific facts and battles are long forgotten. I think this is the strongest defense of modern education, given that we do spend lots of time teaching kids things they will definitely forget. But how would you test it?
Surf

Surf is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 12, 2022 and September 12, 2022. The archive places it in contexts such as "Surf is “a platform for helping people make new friends”". It most often appears alongside Astralcodexten Com, Atlanta, Berkeley.

Reference entry
Surf
Mention count
1
Issue count
1
First seen
September 12, 2022
Last seen
September 12, 2022
September 12, 2022 · Original source
3: I said I’d put this on the last classifieds thread and then forgot - Surf is “a platform for helping people make new friends”; they’re interested in users and advice on how to make it better.
Surface Book 3

Surface Book 3 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 05, 2021 and April 05, 2021. The archive places it in contexts such as "I have bought a Surface Book 3 laptop". It most often appears alongside 2020 presidential election, Adversarial Collaboration Contest, Alaska.

Reference entry
Surface Book 3
Mention count
1
Issue count
1
First seen
April 05, 2021
Last seen
April 05, 2021
April 05, 2021 · Original source
ECON AND TECH: 37. Dow is above 25,000: 70% 38. …above 30,000: 20% 39. Bitcoin is above $5,000: 70% 40. …above $10,000: 20% 41. I have bought a Surface Book 3 laptop: 60% 42. Crew Dragon reaches orbit: 80% 43. Starship reaches orbit: 40%
Swanson

Swanson is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "Swanson than justified". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
Swanson
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
Regarding the overages, I agree that it’s better to penalize something more for an underage than an overage, but I am still not sure this is good communication. Consider for example their bacopa rankings. Just looking at this, I would come away with the conclusion “no bacopa is entirely trustworthy, but at least ND and PE are better than Swanson”. But if I’m understanding right, the whole ranking is entirely driven by overages, and nobody (including the brand getting a C-) has any other problem. I suppose it’s fair to, if everything is exactly the same, rank based on a minor issue, but I think if I didn’t understand what was going on here I would be much more concerned about Swanson than justified.
Swiss Cheese

Swiss Cheese is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 16, 2022 and May 16, 2022. The archive places it in contexts such as "open my fridge and eat a Swiss Cheese slice". It most often appears alongside adaptation-executors, AM, Dynomight.

Reference entry
Swiss Cheese
Mention count
1
Issue count
1
First seen
May 16, 2022
Last seen
May 16, 2022
May 16, 2022 · Original source
Consider evolution, optimizing the fitness of animals. For a long time, it did so very mechanically, inserting behaviors like “use this cell to detect light, then grow toward the light” or “if something has a red dot on its back, it might be a female of your species, you should mate with it”. As animals became more complicated, they started to do some of the work themselves. Evolution gave them drives, like hunger and lust, and the animals figured out ways to achieve those drives in their current situation. Evolution didn’t mechanically instill the behavior of opening my fridge and eating a Swiss Cheese slice. It instilled the hunger drive, and I figured out that the best way to satisfy it was to open my fridge and eat cheese.
t-shirts

t-shirts is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 16, 2026 and January 16, 2026. The archive places it in contexts such as "The quote became a popular sensation, inspiring t-shirts". It most often appears alongside Adams, Alice, All-Seeing Eye.

Reference entry
t-shirts
Mention count
1
Issue count
1
First seen
January 16, 2026
Last seen
January 16, 2026
January 16, 2026 · Original source
The niche that became Dilbert opened when Garfield first said “I hate Mondays”. The quote became a popular sensation, inspiring t-shirts, coffee mugs, and even a hit single. But (as I’m hardly the first to point out) why should Garfield hate Mondays? He’s a cat! He doesn’t have to work!
But t-shirts saying “Working Hard . . . Or Hardly Working?” no longer hit as hard as they once did. Contra the usual story, Millennials are too earnest to tolerate the pleasant contradiction of saying they hate their job and then going in every day with a smile. They either have to genuinely hate their job - become some kind of dirtbag communist labor activist - or at least pretend to love it. The worm turns, all that is cringe becomes based once more and vice versa. Imagine that guy boasting to his date again. One says: “Oh yeah, I grudgingly clock in every day to give my eight hours to the rat race, but trust me, I’m secretly hating myself the whole time”? The other: “I work for a boutique solar energy startup that’s ending climate change - saving the environment is my passion!” Zoomers are worse still: not even the fig leaf of social good, just pure hustle.
Taiwanese chips

Taiwanese chips is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 21, 2022 and November 21, 2022. The archive places it in contexts such as "They got the Taiwanese chips". It most often appears alongside Asterciskmag.com, China, CHIPS act.

Reference entry
Taiwanese chips
Mention count
1
Issue count
1
First seen
November 21, 2022
Last seen
November 21, 2022
November 21, 2022 · Original source
They got the Taiwanese chips, the plant-based chicken, the expensive Korean food, and the nuclear hot sauce. But nobody caught that the refreshment was a white wine dyed red.
Talon

Talon is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "I use a tool called Talon that lets me control my computer by voice". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Reference entry
Talon
Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#95: Make Programming By Voice More Practical I'm Michael Arntzenius (rntz.net) and I'd like $5-40K to work on making programming by voice more practical. Many programmers at some point suffer from repetitive strain injuries (RSI) that make typing difficult; I'm one. To mitigate this I use a tool called Talon that lets me control my computer by voice. Thanks to recent advances, voice control is increasingly practical, and voice programmers form a small but rapidly growing community. However, idioms and tools for coding by voice are in their infancy. I believe now is the right time to push hard on voice-oriented editing: the underlying voice recognition tech is ready, we have a creative, dedicated community willing to experiment with new approaches, and mature editor technology like language servers and online error-robust parsing (eg. tree-sitter) supports editing commands at a higher level than character-by-character. Specifically, this money could support me working part-time for 6 months ($5k) up to full time for 2 years ($40K). I could work on: contributing to Cursorless, the state-of-the-art open-source voice editing framework for VSCode; porting cursorless to other editors to increase its reach; incorporating ideas from recent research on structural editing and typed holes; and on my duties as co-maintainer of the de-facto default Talon script-set. If you're interested, contact me at daekharel@gmail.com.
Tamagotchi

Tamagotchi is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 20, 2025 and November 20, 2025. The archive places it in contexts such as "people went crazy over Tamagotchi, a 'virtual pet simulation game'". It most often appears alongside AI consciousness, AlphaGo, Anthropic.

Reference entry
Tamagotchi
Mention count
1
Issue count
1
First seen
November 20, 2025
Last seen
November 20, 2025
November 20, 2025 · Original source
The argument in favor: people love treating things as conscious. In the 1990s, people went crazy over Tamagotchi, a “virtual pet simulation game”. If you pressed the right buttons on your little egg every day, then the little electronic turtle or whatever would survive and flourish; if you forgot, it would sicken and die. People hated letting their Tamagotchis sicken and die! They would feel real attachment and moral obligation to the black-and-white cartoon animal with something like five mental states.
I never had a Tamagotchi, but I had stuffed animals as a kid. I’ve outgrown them, but I haven’t thrown them out - it would feel like a betrayal. Offer me $1000 to tear them apart limb by limb in some horrible-looking way, and I wouldn’t do it. Relatedly, I have trouble not saying “please” and “thank you” to GPT-5 when it answers my questions.
Tamiflu

Tamiflu is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 28, 2021 and January 28, 2021. The archive places it in contexts such as "Tamiflu cures the flu by blocking flu viruses". It most often appears alongside AD, anxiety, autism spectrum.

Reference entry
Tamiflu
Mention count
1
Issue count
1
First seen
January 28, 2021
Last seen
January 28, 2021
January 28, 2021 · Original source
(this has another implication: stimulants shouldn’t be thought of as magic bullets that “cure” “ADHD” by fixing the underlying cause, in the same way that Tamiflu cures the flu by blocking flu viruses. They should be thought of as things that affect the underlying stew of variables that cause ADHD in some helpful way. By comparison, giving someone a college scholarship might help them become richer, but it’s not “curing” “the” “cause” of “poverty” in a way that flips them from a “not rich” to a “rich” status.)
Tantaliser’s

Tantaliser’s is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 02, 2021 and August 02, 2021. The archive places it in contexts such as "a branch of Tantaliser’s fast food chain does a brisk trade". It most often appears alongside AgroAlpha, Alex Tabarrok, Amazon.

Reference entry
Tantaliser’s
Mention count
1
Issue count
1
First seen
August 02, 2021
Last seen
August 02, 2021
  • 21 August 02, 2021
August 02, 2021 · Original source
On Holiness Avenue, a branch of Tantaliser’s fast food chain does a brisk trade. There is an on-site post office, a supermarket, a dozen banks, furniture makers and mechanics’ workshops. An aerodrome and a polytechnic are in the works. [...]
Target

Target is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2022 and June 23, 2022. The archive places it in contexts such as "Target and CVS pretend to care about shoplifting". It most often appears alongside 1978, 2016 essay, A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs.

Reference entry
Target
Mention count
1
Issue count
1
First seen
June 23, 2022
Last seen
June 23, 2022
June 23, 2022 · Original source
Alyssa Vance investigates whether housing costs predict homelessness at the level of US states, and finds that they do, r^2 = 0.69. The outlier below is DC; removing it brings the correlation to 0.73. I was suspicious of using a state-based analysis to talk about cities, so I repeated her work with the 50 biggest US cities, using two different sets of price data - one from Kiplinger, one from Zillow. I found the Zillow numbers a little more plausible; here they are:
I was suspicious of using a state-based analysis to talk about cities, so I repeated her work with the 50 biggest US cities, using two different sets of price data - one from Kiplinger, one from Zillow. I found the Zillow numbers a little more plausible; here they are: This was slightly lower, r^2 = 0.42, but still pretty good! I also don’t think my city homelessness data were perfect (people report homelessness data not by city but by “continuum of care area”, and it’s complicated to figure out what the overall population of each area is), so it wouldn’t surprise me if that’s responsible for most of the decay from Alyssa’s analysis to mine. Here you can see that San Francisco has a pretty high homelessness rate, but no worse than some other big cities like DC, Boston, and New York (Shellenberger, to his credit, mentions this in the book). So how come everyone talks about SF all the time? Alyssa gives two main reasons. First, SF homeless tend to concentrate in a few areas downtown; this is also where a lot of the tourists and businesspeople are, so the average tourist or businessperson in San Francisco sees a lot more homeless people than they would if they were evenly distributed throughout the city. And second, SF homeless are less likely to be sheltered than homeless people elsewhere; Shellenberger notes that “over 99% of New York’s homeless have access to shelter. In San Francisco, just 42% do” (see here for other cities). Source is here; I think “street homeless” means the same as “unsheltered” We’ll talk more in Part 4 about why this might be, but one common theory is climate: San Francisco has year-round above-freezing temperatures, so there’s less urgency to shelter everyone. Alyssa shows that the relationship between temperature and percent unsheltered is strong: That regression line looks suspicious, but I hear computers are never wrong. So one possible conclusion is that SF has around the amount of homelessness you would predict from its very high housing prices, and around the percent unsheltered you would predict from its balmy winter weather, and there’s nothing further to be explained. Shellenberger does not like this conclusion. San Francisco’s mild climate alone cannot explain why it has more homeless people than other cities. Miami, Phoenix, and Houston have year-round warm weather and far fewer homeless than San Francisco per capita. Per capita homelessness in San Francisco, Greater Miami, Greater Phoenix, and Greater Houston in 2020 was 9.3, 1.3, 1.6, and 0.8 per 1,000 residents, respectively. And Greater Miami, Greater Phoenix, and Greater Houston saw their per capita homeless population decline from 2005 to 2020 by 39, 17, and 74 percent while San Francisco saw its rise 30 percent. Nor can housing prices explain the discrepancy. Palo Alto and Beverly Hills have mild climates and expensive housing but don’t have San Francisco’s homeless problem. As for the Zillow study that was reported to find a correlation between rising rents and homelessness, a deeper look at the research reveals a more nuanced finding. Homelessness and affordability are correlated only in the context of certain “local policy efforts [and] social attitudes,” concluded researchers. This feels like kind of a shell game. San Francisco’s mild climate alone can’t explain why it has more homeless people per capita than Miami or Houston. But as the graph above shows, housing prices do explain about 75% of the difference between SF and those two cities. But because the book talks about the Miami-SF discrepancy in the paragraph about climate instead of the paragraph about prices, it makes it sound like a mystery that neither prices nor climate can explain. The Zillow article mentioned is Homelessness Rises Faster Where Rents Exceed A Third Of Incomes, which is based on this study. Shellenberger’s summary is not really the researchers’ conclusion. The article does mention “local attitudes” and “social policy” once, but only to explain that the paper includes a term representing “latent factors” that they’re not going to bother distinguishing from each other in their model, and some of those terms could be local policy or social attitudes. Later they mention there are some outliers in their model (eg Houston), and it would be reasonable to assume that the latent factors help explain the outliers, but they don’t give us any reason to think that this is more interesting than the fact that every model ever will have outliers. But also, this is one study by Zillow. Alyssa and I both tried the same analysis, and found the same thing, with a correlation that’s unusually high for this kind of work. Sure, there are outliers, but San Francisco isn’t one of them. San Francisco is only a couple of percent off where the regression line would predict. That leaves the point about Palo Alto and Beverly Hills. They “have mild climates and expensive housing but don’t have San Francisco’s homeless problem”. At first I felt like this was cheating - yeah, rich suburbs don’t have lots of homelessness, come on. But “rich” and “high property values” are pretty close to synonyms. If you’re going to say that high property values cause homelessness, isn’t it in fact pretty surprising that rich suburbs don’t have it? In fact, if you’re a homeless person, why wouldn’t you want to live in a suburb? Quieter (so probably easier to sleep at night) more places out of sight to pitch tents, less crime (important if you’re living on the street!), and potentially lower cost of living in terms of food and goods. I tried looking into this issue and found explanations like: Usually it’s poor people who become homeless. Cities have more poor people than suburbs, because they have more rental units, small apartments, public transportation, and blue-collar jobs. Suburbs, by natural consequence of their layout, enforce a certain wealth minimum before people can live there, and people above that wealth minimum rarely lose everything and become homeless. It’s strange that poor people tend to live in cities (ie places with very high land values), and you have to wonder whether there are ways that could be different, but it does seem true.
This was slightly lower, r^2 = 0.42, but still pretty good! I also don’t think my city homelessness data were perfect (people report homelessness data not by city but by “continuum of care area”, and it’s complicated to figure out what the overall population of each area is), so it wouldn’t surprise me if that’s responsible for most of the decay from Alyssa’s analysis to mine. Here you can see that San Francisco has a pretty high homelessness rate, but no worse than some other big cities like DC, Boston, and New York (Shellenberger, to his credit, mentions this in the book). So how come everyone talks about SF all the time? Alyssa gives two main reasons. First, SF homeless tend to concentrate in a few areas downtown; this is also where a lot of the tourists and businesspeople are, so the average tourist or businessperson in San Francisco sees a lot more homeless people than they would if they were evenly distributed throughout the city. And second, SF homeless are less likely to be sheltered than homeless people elsewhere; Shellenberger notes that “over 99% of New York’s homeless have access to shelter. In San Francisco, just 42% do” (see here for other cities). Source is here; I think “street homeless” means the same as “unsheltered” We’ll talk more in Part 4 about why this might be, but one common theory is climate: San Francisco has year-round above-freezing temperatures, so there’s less urgency to shelter everyone. Alyssa shows that the relationship between temperature and percent unsheltered is strong: That regression line looks suspicious, but I hear computers are never wrong. So one possible conclusion is that SF has around the amount of homelessness you would predict from its very high housing prices, and around the percent unsheltered you would predict from its balmy winter weather, and there’s nothing further to be explained. Shellenberger does not like this conclusion. San Francisco’s mild climate alone cannot explain why it has more homeless people than other cities. Miami, Phoenix, and Houston have year-round warm weather and far fewer homeless than San Francisco per capita. Per capita homelessness in San Francisco, Greater Miami, Greater Phoenix, and Greater Houston in 2020 was 9.3, 1.3, 1.6, and 0.8 per 1,000 residents, respectively. And Greater Miami, Greater Phoenix, and Greater Houston saw their per capita homeless population decline from 2005 to 2020 by 39, 17, and 74 percent while San Francisco saw its rise 30 percent. Nor can housing prices explain the discrepancy. Palo Alto and Beverly Hills have mild climates and expensive housing but don’t have San Francisco’s homeless problem. As for the Zillow study that was reported to find a correlation between rising rents and homelessness, a deeper look at the research reveals a more nuanced finding. Homelessness and affordability are correlated only in the context of certain “local policy efforts [and] social attitudes,” concluded researchers. This feels like kind of a shell game. San Francisco’s mild climate alone can’t explain why it has more homeless people per capita than Miami or Houston. But as the graph above shows, housing prices do explain about 75% of the difference between SF and those two cities. But because the book talks about the Miami-SF discrepancy in the paragraph about climate instead of the paragraph about prices, it makes it sound like a mystery that neither prices nor climate can explain. The Zillow article mentioned is Homelessness Rises Faster Where Rents Exceed A Third Of Incomes, which is based on this study. Shellenberger’s summary is not really the researchers’ conclusion. The article does mention “local attitudes” and “social policy” once, but only to explain that the paper includes a term representing “latent factors” that they’re not going to bother distinguishing from each other in their model, and some of those terms could be local policy or social attitudes. Later they mention there are some outliers in their model (eg Houston), and it would be reasonable to assume that the latent factors help explain the outliers, but they don’t give us any reason to think that this is more interesting than the fact that every model ever will have outliers. But also, this is one study by Zillow. Alyssa and I both tried the same analysis, and found the same thing, with a correlation that’s unusually high for this kind of work. Sure, there are outliers, but San Francisco isn’t one of them. San Francisco is only a couple of percent off where the regression line would predict. That leaves the point about Palo Alto and Beverly Hills. They “have mild climates and expensive housing but don’t have San Francisco’s homeless problem”. At first I felt like this was cheating - yeah, rich suburbs don’t have lots of homelessness, come on. But “rich” and “high property values” are pretty close to synonyms. If you’re going to say that high property values cause homelessness, isn’t it in fact pretty surprising that rich suburbs don’t have it? In fact, if you’re a homeless person, why wouldn’t you want to live in a suburb? Quieter (so probably easier to sleep at night) more places out of sight to pitch tents, less crime (important if you’re living on the street!), and potentially lower cost of living in terms of food and goods. I tried looking into this issue and found explanations like: Usually it’s poor people who become homeless. Cities have more poor people than suburbs, because they have more rental units, small apartments, public transportation, and blue-collar jobs. Suburbs, by natural consequence of their layout, enforce a certain wealth minimum before people can live there, and people above that wealth minimum rarely lose everything and become homeless. It’s strange that poor people tend to live in cities (ie places with very high land values), and you have to wonder whether there are ways that could be different, but it does seem true.
Telegram

Telegram is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 09, 2023 and October 09, 2023. The archive places it in contexts such as "the Telegram bot for Telegram-based prediction markets". It most often appears alongside Academic Decathlon, ACX Grants, ACX/rat/EA community.

Reference entry
Telegram
Mention count
1
Issue count
1
First seen
October 09, 2023
Last seen
October 09, 2023
October 09, 2023 · Original source
Enjoy the public goods we’ve produced. The Crystal Ballin’ Podcast has one episode and is hoping to make more (as are their competitors, the Market Manipulation Podcast). OPTIC is looking for participants and volunteers. You can still use Manifolio to make Kelly bets, the Telegram bot for Telegram-based prediction markets, and the browser extension to see what Manifold markets people are betting on. And although it’s not technically one of ours, I still like The Base Rate Times.
Tenga

Tenga is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 03, 2025 and June 03, 2025. The archive places it in contexts such as "Tenga Arte Drape Testosterone". It most often appears alongside ACX Commentariat, Arnold Schoenberg, Baldur's Gate 3.

Reference entry
Tenga
Mention count
1
Issue count
1
First seen
June 03, 2025
Last seen
June 03, 2025
June 03, 2025 · Original source
...Schools - A Review (by EN) Scientific Peer Review Sheldon Brown's Bicycle Technical Info Sign-Tracking Sucks State Of Competitive Debating (Unions) Address Synanthropes Tenga Arte Drape Testosterone The ACX Commentariat The Delusion Of Infinite Economic Growth The Drum Major Instinct The Emperor Of All Maladies The Internet That Might Have Be...
...Schools - A Review (by EN) Scientific Peer Review Sheldon Brown's Bicycle Technical Info Sign-Tracking Sucks State Of Competitive Debating (Unions) Address Synanthropes Tenga Arte Drape Testosterone The ACX Commentariat The Delusion Of Infinite Economic Growth The Drum Major Instinct The Emperor Of All Maladies The Internet That Might Have Been The Life's Work Of Ba...
Tesla Roadster

Tesla Roadster is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 13, 2023 and September 13, 2023. The archive places it in contexts such as "The same thing happened with the Tesla Roadster and the Model S". It most often appears alongside Abe Lincoln, AI alignment movement, Ambras.

Reference entry
Tesla Roadster
Mention count
1
Issue count
1
First seen
September 13, 2023
Last seen
September 13, 2023
September 13, 2023 · Original source
When SpaceX was on its last few hundred thousand dollars, and the Falcon 1 kept blowing up, and no private company had ever launched a rocket to space before, and they only had a few weeks to make Falcon 1 fly and restore investor confidence before the company went bankrupt - Elon was still putting some of his energy into planning the Falcon 5 and Falcon 9. The same thing happened with the Tesla Roadster and the Model S.
Tesla roadsters

Tesla roadsters is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 16, 2021 and April 16, 2021. The archive places it in contexts such as "Tesla roadsters ... are wealth". It most often appears alongside "The Rent Is Too Damn High!", 16th amendment, 1886.

Reference entry
Tesla roadsters
Mention count
1
Issue count
1
First seen
April 16, 2021
Last seen
April 16, 2021
April 16, 2021 · Original source
Although 2021 seems better than 1879 in absolute material terms, George's complaint still rings true: healthcare and higher education are increasingly unaffordable, inequality is as bad as it ever was, and The Rent Is Too Damn High. And even if all of these measures had improved as well, we still have to contend with a fundamental complaint: how can human civilization have piled up an amount of wealth best described as absolutely banana pants insane, and yetstill have poverty, oppression and cyclical recessions? Yes, greed, evil, and human nature will always be with us, but isn't it weird that we haven't eliminated these economic problems the same way we've eliminated Smallpox, Scurvy, and having to write your scathing polemics about Thomas Jefferson by candlelight with a goose feather? Giving the mic back to George, he closes the chapter with this haunting quote, first written 142 years ago: If there is less deep poverty in San Fran Francisco than in New York, is it not because San Francisco is yet behind new York in all that both cities are striving for? When San Francisco reaches the point where New York now is, who can doubt that there will also be ragged and barefooted children on her streets? I'll just leave this here: Number of Homeless Children in U.S. At All-Time High; California Among Worst States. I. Wages and Capital George insists sloppy terminology leads to sloppy thinking. Naturally, he spends an entire chapter beating words to death to correct this. The Meaning of the Terms Let's start with Wealth. The common usage, both then and now, is "anything with an exchange value." George doesn't like how this mixes dissimilar things. By George, what is wealth? Wealth is produced when Nature's bounty is touched by human labor resulting in a tangible product that is the object of human desire. Labor is required, but the amount and type doesn't matter - George offers the example of simply picking a berry off a bush as an act that transforms nature's gifts into human wealth. Note particularly that human desire is an important requirement of wealth; it doesn't matter how much work someone put into something, if it doesn't gratify human needs or desires in some way, it's not wealth. Speaking of human desire, let's talk about Value. Where does a thing's value come from? The prevailing theory of the day was the Labor Theory of Value which originated with Adam Smith and David Ricardo, which says that Labor is the source of value. The early formulations were a bit ambiguous, here's Smith in Wealth of Nations for instance: The value of any commodity ... is equal to the quantity of labor which it enables him to purchase or command. Labor, therefore, is the real measure of the exchangeable value of all commodities. So... is a thing's value how much labor it takes to make the thing, or how much labor someone's willing to exchange for the thing? Nowadays Labor Theory of Value is most commonly associated with Marx. Marx picks a lane and says the value of something is tied to the amount of "socially necessary labor" required to produce it. George goes the other way: It is never the amount of labor that has been exerted in bringing a thing into being that determines its value, but always the amount of labor that will be rendered in exchange for it. - Henry George, The Science of Political Economy, p. 253 In other words, "a thing's value is whatever someone is willing to pay for it." This is in line with the so-called marginal revolution (the movement, not the blog) and modern theories of value. Labor Labor is the exertion of human beings. It's possible to labor to no avail (try punching a concrete wall), but typically humans labor towards an end, such as gaining wealth. But whether or not we accomplish anything with our efforts, George calls them labor. Labor isn't just making things, by the way – it's also moving or exchanging them. Production Production is labor applied "to the production of wealth." You know, productively. This is all human exertion that isn't punching a concrete wall and rewards you for your efforts with something that fits the definition of wealth. Said wealth is the "product of labor." Wages whatever is received as the result or reward of exertion is "wages." No distinction here is made between blue-collar work and white-collar work – whether one is called "hourly pay" and the other is called "annual salary," George calls them both "wages." It doesn't matter whether you receive them from your boss, from customers, or from nature. If you do work and get something from it, you have received "wages." With those basics under our belt, let's circle back to Wealth: What are some examples of wealth? By George, Gold is wealth. Teddy bears are wealth. Tesla roadsters and candy canes and young adult vampire romance novels are wealth. The same goes for fish you've caught, deer you've hunted, and cool looking rocks you've picked up on your morning walk. The value of these things may differ, but as long as they're tangible, originate in nature, someone ever did a lick of work to make or acquire them, and a human being somewhere desires them for any reason, they're wealth. It gets a little clearer when we ask what isn't wealth. And by George, Money isn't wealth. Articles of gold are wealth because they're tangible things that have been dug up, crafted, and fulfill certain human desires. But paper currency, digital currencies, and other things that aren't inherently valuable but merely represent value are not wealth (outside of putting their physical articles in coin collections or making paper airplanes, and so forth). Now don't get the man wrong, these things are certainly valuable. They're just not wealth. They are certificates that represent claims on wealth. For any computer programmers in the audience, money is a pointer to wealth. Likewise Stocks and Bonds and other financial instruments are not wealth. These are also just claims on wealth. A creditor's title to Debt isn't wealth, either, it's just a claim on the debtor's (typically future) wealth. And, writing as he was not long after the Civil War, George points out that Slaves are not wealth either but, represent "merely the power of one class to appropriate the earnings of another class." Wealth, thus defined, is the terminal "ground truth" bits of the economy, and all the financial layers on top are fancy IOUs that just encode various claims on it. George offers a thought experiment to test if something is wealth: if you produce a pile of gold, fish, or Lego bricks, you've clearly increased the amount of wealth in the world. But if you produce a giant pile of IOUs that just records who owns what and who owes what to whom, it doesn't matter how many of them you pile up or how long the chains of ownership get, you still haven't increased the amount of real wealth in the world. Again, this isn't saying the IOUs aren't valuable, they are. But they're only valuable because they ultimately point to real wealth. If you magically transported everyone over to a hypothetical Earth 2, carrying over all of Earth 1's money and financial instruments but none of Earth 1's tangible wealth, the value of all those IOUs would instantly evaporate. Now what about digital goods? Leaving things like Bitcoin aside for the moment, let's consider the case of a digital image file: By George, this is wealth. Digital though it may be, it's physically encoded on a storage device somewhere, and is thus tangible (it's not a pure abstract concept flitting about in Platonic heaven) and has its origins in nature. Human exertion built the computer that encodes it, and clicking the button that saves it to disk or displays it on your screen is labor. Finally, it directly satisfies human desires (mine, at the very least). It's value may be negligible, but it's wealth. By contrast, the digital bit sitting in some database that says I own a particular eBook or mp3 is just a digital IOU – a claim on the wealth that are the physical bits on my local storage device or remote server that digitally encodes the files. The fact that digital files don't seem particularly physical, and that they can be trivially and endlessly copied, doesn't mean that Henry George, magically transported to today, wouldn't regard them as wealth. Okay, so is there anything else that's not wealth? By George, Bitcoin isn't wealth, in case you were wondering. It's just a (very fancy) financial instrument, a digital claim on wealth. And that goes for most crypto assets – a token on some blockchain that says I own a painting by Banksy is just another IOU, regardless of the technical sophistication of its distributed trustless ledger. What about intellectual property? Copyrights, patents, and trademarks are all different forms of Monopoly – the exclusive, government-granted legal right to do a particular thing (publish a certain book, manufacture a certain product, use a certain name in business, etc). The exclusive right to do or produce a thing, valuable as it may be, is not the thing itself. By George, Monopoly is not wealth. But there is something big that is wealth – the C-word. Capital. By George, Capital is "wealth devoted to procuring more wealth", and it's the next thing he insists everyone is hopelessly confused about. He quotes Adam Smith, agreeing with him thus far: That part of a man's stock which he expects to afford him revenue is called his capital. ...and also gives us a short etymology lesson on the origin of the term: The word capital, as philologists trace it, comes down to us from a time when wealth was estimated in cattle, and a man's income depended upon the number of head he could keep for their increase. ("Per capita" being the Latin for "by head") By George, all capital is wealth, but not all wealth is capital. George notes capital is often described as being "stored up labor", and endorses this view – but what it really means, is capital is stored up production. It's not literally the labor that's stored up but the wealth generated by it, set aside and then dedicated to the purpose of getting more wealth. George insists that it is the owner's intention that transforms wealth into capital. If you buy an old factory to throw parties in for your hipster friends, it's just wealth. But the minute you decide to put it to work to make something useful (or start charging your hipster friends a cover charge at the door), it becomes capital. George therefore further insists that a laborer's daily bread and the clothes on their back do not count as capital, because a person has to eat and wear clothes whether they work or not. The laborer's tools (and arguably their steel-toed work boots) can however be counted as capital, because their purpose is to assist the laborer in getting more wealth by working for wages, and the laborer wouldn't acquire, use, and maintain those things otherwise. George has more exclusions: We must exclude from the category of capital everything that may be included either as land or labor. Human exertion (labor) by itself can never be capital. The products of human labor become capital when they are stored up and set to the purpose of getting more wealth. To muddle this distinction defeats the point of having separate terms for those things at all, and prevents us from reasoning meaningfully about how they relate to one another. Labor is not capital, and neither is labor by itself wealth, it produces wealth – and if it ain't wealth, it ain't capital. And that brings us to land. Land, land, land. By George, land is not wealth. And it's definitely not capital. The unique specialness of land is George's entire schtick and the very core of his philosophy. The term land embraces, in short, all natural materials, forces, and opportunities That means that a field or a meadow is "land", as is a mountain. But so are the fish in the sea, the clouds in the sky, veins of gold in the earth's crust, and the oil deep under ground. These things aren't yet wealth – not until human beings both a) desire them and b) touch them with labor. So... land is not wealth. But... how come? I mean, look: land is tangible, it "comes from nature", humans are always productively applying their labor to it, and it certainly seems capable of gratifying human desires. George sees this reasoning as understandable, but insists it's the root mistake that leads other political economists astray – because for George, land just is nature itself. Come again? Land is the ultimate source of all wealth, but it's most useful to think of it as a generator, acompletely separate entity from the wealth that human labor and desire draws from it. Players of Magic: the Gathering and Settlers of Catan should already have a solid grasp of this distinction: In modern times, George would grant electromagnetic spectrum and orbital real estate for satellites the same status of "land" that already applies to farmland and terrestrial real estate. We don't even need to speculate about whether he'd attach this status to sunlight because he straight-up predicted solar power: Even the lack of rain which makes some parts of the globe useless to man, may, if invention ever succeeds in directly utilizing the power of the sun's rays, be found to be especially advantageous for certain parts of production. (That's from Protection or Free Trade, footnote 19) The important thing to grasp about land is that it comes before everything humans do or make, and is itself a thing no human can make. Okay, smarty-pants, what about the Netherlands? They've been making land for centuries! Well, land in the Georgist sense doesn't refer simply to "dry land", but also the sea bed, the oceans, and the skies above. The "new land" in the Netherlands counts as an improvement to land that already existed. The seabed was always there, but by filling it in so you can walk around on it, now it's more useful to us (George has a lot to say about improvements to land, which we'll get to later). Okay, what is land not? nothing that is freely supplied by nature can be properly classed as capital By George, land is not wealth. And since it's not wealth, it's not capital. Okay, we get it. Land is very special to Mr. George and we must never put it in the same category as wealth, labor, capital, wages, production, money, or anything else. Why exactly is this so damn important? Well, by George, if you treat land the same way you would a bar of pig iron, an hour of work, or a dollar bill, before you know it you'll get poverty paradoxically advancing alongside progress, inexplicable bouts of industrial depression, literal genocides and holocausts (he's dead serious about this), and The Rent Being Too Damn High. With terminology now firmly established, George moves on to the relationship between wages and capital. 3-for-1 special on Wages, Capital, and Labor I'm condensing three chapters here because they all deal with the same basic thing. The question George wants to answer is: Why, in spite of increase in productive power, do wages tend to a minimum which will give but a bare living? The conventional wisdom of George's time is that wages are governed by a fixed ratio between the number of laborers and the amount of capital devoted to their employment, because "the increase in the number of laborers tends naturally to follow and overtake any increase in capital." So it doesn't matter how much capital you throw at employing workers, it'll just attract even more workers splitting it up, so although wages might temporarily wiggle a bit in the long term they'll always settle back to a "natural" minimum. (As we'll see in the next section, this argument stems from Malthusianism). George spends some time methodically poking holes in the theory (it's predictions don't line up with the facts he observes), and then sets out to prove his replacement theory (emphases mine): wages, instead of being drawn from capital, are in reality drawn from the product of the labor for which they are paid. He pulls a G.K. Chesterton to make his point: During the time [the laborer] is earning the wages he is advancing capital to his employer, but at no time, unless wages are paid before work is done, is the employer advancing capital to him. He starts by identifying the source of confusion: Because wages are generally paid in money, and in many of the operations of production are paid before the product is fully completed, or can be utilized, it is inferred that wages are drawn from pre-existing capital I mean, the old theory seems sensible: the employer has capital and uses it to pay wages. But however you slice it, capital's investment gets paid back by production when it takes its cut, so does it even make a difference to talk about where wages are "drawn" from? Value goes out, value comes in, isn't it all a wash? By George, it isn't: in the old theory, because capital "must come first", it follows that "industry is limited by capital - that capital must be accumulated before labor is employed", which leads to a reductio ad absurdum – We are told that capital is stored-up or accumulated labor – "that part of wealth which is saved to assist future production." If we substitute for the word "capital" this definition of the word, the proposition carries its own refutation, for that labor cannot be employed until the results of labor are saved becomes too absurd for discussion. George anticipates the following rejoinder – Well, when we say 'labor is paid out of capital' we don't mean it as an absolute statement for all stages of human development (or else we have a chicken-and-the-egg problem and civilization could never have begun), we just mean it applies to, say, every civilization that's left the stone age. George will have none of it and spends three entire chapters relentlessly beating to death the idea that wages are drawn from capital instead of from production. He starts with the simple case where wages are paid in the form of direct, concrete wealth, then moves on to the more complex case where people are paid in money and other instruments. Laboring for wages: Imagine a fishing village where nobody cooperates – each person digs their own bait and catches their own fish. Then they discover labor specialization and realize they can catch more fish together if one specializes in digging and the other in catching. So the digger digs, the catcher catches, and they share the fish. The digger really contributes as much to the catch as the one who physically pulls the fish off the hook even though the digger never directly "caught" a fish, and the fish he gets for his work is directly paid out of his contribution to the total production. Later, our fisherfolk invent canoes, and one stays home making and repairing canoes. This increases the haul of the digger and catcher, and the canoe-er gets paid out of her contribution to the increased production. And so it goes as society continues to advance. The work the specialist puts in causes more fish to be caught, and that person's wages is drawn from the growing pile of fish. As George puts it: "Earning is making." George gives another example: If I take a piece of leather and work it up into a pair of shoes, the shoes are my wages – the reward of my exertion. Surely they are not drawn from capital – either my capital or any one else's capital – but are brought into existence by the labor of which they become the wages; and in obtaining this pair of shoes as the wages of my labor, capital is not even momentarily lessened one iota... As my labor goes on, value is steadily added, until, when my labor results in the finished shoes, I have my capital plus the difference in value between the material and the shoes. And another: If I hire a man to gather eggs, to pick berries, or to make shoes, paying him from the eggs, the berries, or the shoes that his labor secures, there can be no question that the source of the wages is the labor for which they are paid. George goes on to say it doesn't matter if you're paid in money or directly in wealth, because the money is a direct claim on the underlying wealth. It also doesn't matter if you get paid on commission. Imagine a whaling ship where each crewman gets paid a share out of whatever the ship catches. When the ship sails back into port with a hold full of whale oil and bone, the crew gets paid in money, the owner simultaneously adds to his capital oil and bone. The crew's money directly represents their share of the concrete wealth that is the oil and bone. The owner's capital hasn't decreased, and the workers drew their wages directly from the production. So let's get to the point, Mr. George – wages aren't drawn from capital but instead from production. Great, let's grant that – so what? George hammers away at this because thinking wages are drawn from capital leads to a false conclusion, namely that "labor cannot exert its productive power unless supplied by capital with maintenance." "Maintenance?" Well, workers need food and clothing and they get paid by their employers, so you could imagine capital as a limiting factor on labor. But by George, food and clothing isn't capital, it's just wealth, as we said before. And with regard to wages, the point is that the employer always gets "paid" first, because the second the laborer produces value, the employer's capital increases: As in the exchange of labor for wages the employer always gets the capital created by the labor before he pays out capital in the wages, at what point is his capital lessened even temporarily? Okay, but what if I'm just a terrible businessman and I pay somebody $500 an hour to smash Ming vases, then sell the fragments as aggregate to a construction crew for a few pennies a pound, all at a tremendous loss? Surely then the laborer's wages must be drawn from my capital, because there's not enough productive value generated by the labor to draw them from! George says okay, sure, but only because I'm an idiot and will soon be out of business: Yet, unless the new value created by the labor is less than the wages paid, which can be only an exceptional case, the capital which he had before in money he now has in goods – it has been changed in form, but not lessened. Fair enough, Mr. George, but what if I'm building some enormously expensive multi-decade project, like a dam or a nuclear power plant or a cathedral? The kind of thing we call a "capital-intensive" project? What do you have to say to that? George points out that as laborers labor, they progressively add value to whatever they're producing. Take the case of a shipwright building ships for an employer – even if the boss can't sell a half-finished ship, it still holds value (for one, it costs less to finish a half-finished ship then no ship at all). And with every stroke of the laborer's work, the employer who owns the shipyard gets an incremental increase in his stock of capital. It is not the last blow, any more than the first blow, that creates the value of the finished product – the creation of value is continuous, it immediately results from the exertion of labor. A pedant would point out that the "last hit" that finishes the product which makes it ready for market adds disproportionate value, but George's point is just to establish that value is continuously created, and doesn't magically come into being allat once right at the end. George further points out that if you look at things like agriculture you'll see the market directly acknowledging his theory: As a plowed field will bring more than an unplowed field, or a field that has been sown more than one merely plowed... It is tangible in the case of orchards and vineyards which, though not yet in bearing, bring prices proportionate to their age. George freely admits that capital can be required for certain kinds of work, but he disagrees with what its purpose is. It's not a pool that wages get paid out of. He goes on for another chapter on "The Maintenance of Laborers Not Drawn From Capital" but I think we can safely skip it and move on. TL:DR – George hammers to absolute death the idea that Laborers derive their own maintenance (food/shelter/clothing/etc) from their wages, with George insisting it is drawn from production and... you guessed it, not from capital. At least some of George's ideas will not seem so radical to modern readers (especially those already critical of capitalism or neoclassical economics), but it's important to understand that at the time almost everything he was saying was considered deeply radical and shocking. Capital was the fundamental driving force of the economy and labor was utterly dependent on it, and the Malthusian theory of overpopulation was the accepted explanation for why wages were low and workers were starving. Political Cartoon literally demonizing Henry George – Puck magazine Oct. 20, 1886 The Real Functions of Capital Okay, Mr. George. You've spent three whole chapters beating me over the head with what the functions of capital aren't. So what are the functions of capital? Capital "increases the power of labor to produce wealth." How? By enabling labor to apply itself more effectively (power tools go brrrr)
Tether

Tether is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 08, 2022 and December 08, 2022. The archive places it in contexts such as "One of the stablecoins counted as “not losing their pegs” here is Tether, which everyone including me suspects is at least kind of a scam". It most often appears alongside ACX, Africa, Best Crypto Exchanges Of 2020.

Reference entry
Tether
Mention count
1
Issue count
1
First seen
December 08, 2022
Last seen
December 08, 2022
December 08, 2022 · Original source
One of the stablecoins counted as “not losing their pegs” here is Tether, which everyone including me suspects is at least kind of a scam. But somehow nothing has gone wrong so far, so it’s not showing up as a scam in the statistics. Still, feel free to count it that way if you want, in which case the scam rate would go up to 1/54, and the expected stablecoin depeg rate would go to 3/10.
TG4050

TG4050 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 10, 2024 and May 10, 2024. The archive places it in contexts such as "patients treated with TG4050 have remained disease-free". It most often appears alongside "Most Drugs Are Bad For You", 1123581321, California.

Reference entry
TG4050
Mention count
1
Issue count
1
First seen
May 10, 2024
Last seen
May 10, 2024
May 10, 2024 · Original source
Docs are reluctant to impose systemic chemo because of the side effects. But Transgene has a personalized vaccine that is supposed to prevent HNSCC recurrence: https://www.nec.com/en/press/202304/global_20230418_01.html: "In the head and neck cancer trial to date, all patients treated with TG4050 have remained disease-free, despite unfavorable systemic immunity and tumor micro-environment before treatment," And most of these personalized vaccines have essentially no side effects.
But that should change! Part of the reason I'm so frustrated by the FDA is that mRNA-4157 and TG4050 should already be available for HNSCC. Instead, they're stuck in trial hell, while HNSCC patients like me suffer recurrences and then die.
thalidomide

thalidomide is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 20, 2021 and August 20, 2021. The archive places it in contexts such as "she exposed the side effects of the dangerous drug thalidomide". It most often appears alongside ACT/SSC, aducanumab, aducanumab.

Reference entry
thalidomide
Mention count
1
Issue count
1
First seen
August 20, 2021
Last seen
August 20, 2021
August 20, 2021 · Original source
"At the FDA, he was a friend and supporter of his colleague Frances Kelsey as she exposed the side effects of the dangerous drug thalidomide. Informed by her experience, Nestor’s tenure at the FDA was marked by obstructionism. In a four-year stretch from 1968 to 1972, he approved zero new drugs for use by the public, viewing the risks and uncertainties still too great. As a result, he was moved to a do-nothing job within the administration. He protested, and was later reinstated and given an apology by the agency."
The Boring Company

The Boring Company is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2023 and September 18, 2023. The archive places it in contexts such as "About The Boring Company". It most often appears alongside 787, adderallposting, ADL.

Reference entry
The Boring Company
Mention count
1
Issue count
1
First seen
September 18, 2023
Last seen
September 18, 2023
September 18, 2023 · Original source
1: Comments From People With Personal Experience 2: ...Debating Musk's Intelligence 3: ...Debating Musk's Mental Health 4: ...About Tesla 5: ...About The Boring Company 6: ...About X/Twitter 7: ...About Musk's Mars Plan 8: ...Comparing Musk To Other Famous Figures 9: Other Comments 10: Updates
5: Comments About The Boring Company The Boring Company got brought up as an example that Musk doesn’t bat 1000. But is it a real failure? It’s valued at $6 billion and working on digging a tunnel underneath Las Vegas. Commenters weigh in:
The Boring Company got brought up as an example that Musk doesn’t bat 1000. But is it a real failure? It’s valued at $6 billion and working on digging a tunnel underneath Las Vegas. Commenters weigh in:
THE BURROWING COMPANY

THE BURROWING COMPANY is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 12, 2023 and December 12, 2023. The archive places it in contexts such as "a guy in a t-shirt that says 'THE BURROWING COMPANY'". It most often appears alongside 2024, Aaron Peskin, accelerationist conspiracy.

Reference entry
THE BURROWING COMPANY
Mention count
1
Issue count
1
First seen
December 12, 2023
Last seen
December 12, 2023
December 12, 2023 · Original source
You do find yourself oddly driven to keep munching on the potato chips. Before you become a hopeless addict, you bid Hans and Jonathan good-bye. On your way out of the kitchen, you almost knock over a guy in a t-shirt that says “THE BURROWING COMPANY”.
The Cheesecake Factory

The Cheesecake Factory is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 28, 2022 and December 28, 2022. The archive places it in contexts such as "best known for inventing the phrase 'Don’t Worry, Be Happy' and for being supported by The Cheesecake Factory". It most often appears alongside 2C-B, 48: Bean, @AliceFromQueens.

Reference entry
The Cheesecake Factory
Mention count
1
Issue count
1
First seen
December 28, 2022
Last seen
December 28, 2022
December 28, 2022 · Original source
40: Sufism Reoriented is a cult part of the diverse and beautiful tapestry of American religious life, best known for inventing the phrase “Don’t Worry, Be Happy” and for being supported by The Cheesecake Factory. This article describes their struggle to build a grand Central Temple in the suburbs of the San Francisco Bay Area, pitting NIMBYs against religious freedom advocates (h/t Ozy).
The Pear Ring

The Pear Ring is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 20, 2023 and April 20, 2023. The archive places it in contexts such as "The Pear Ring is a distinctive ring you can wear to signal that you’re single". It most often appears alongside 15 minute cities, 200 Concrete Problems In AI Interpretability, 2022 ACX Forecasting contest.

Reference entry
The Pear Ring
Mention count
1
Issue count
1
First seen
April 20, 2023
Last seen
April 20, 2023
April 20, 2023 · Original source
...ou are!) 21: I’m not sure what this means in real life or why this would have changed, but congratulations to Peter Thiel, I guess: 22: This month in institution design: The Pear Ring is a distinctive ring you can wear to signal that you’re single and interested in people introducing themselves or flirting with you. Good idea in a vacuum, but I’m worr...
...ou are!) 21: I’m not sure what this means in real life or why this would have changed, but congratulations to Peter Thiel, I guess: 22: This month in institution design: The Pear Ring is a distinctive ring you can wear to signal that you’re single and interested in people introducing themselves or flirting with you. Good idea in a vacuum, but I’m worried about the two usual banes of things like this - how do you b...
theanine

theanine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 17, 2022 and May 17, 2022. The archive places it in contexts such as "Maybe theanine, a little?". It most often appears alongside kanna, psilocybin microdosing, SAMe.

Reference entry
theanine
Mention count
1
Issue count
1
First seen
May 17, 2022
Last seen
May 17, 2022
May 17, 2022 · Original source
To put this another way: if you made a model combining some measure of “how hard is this chemical to obtain / how hard is this lifestyle intervention to practice?” and “how novel and high-tech does it feel?”, plus one or two other things like “is this a stimulant?”, it feels like this would predic the results almost perfectly. Does anything stand out as doing substantially worse than the simple model would predict? It really doesn’t. Maybe theanine, a little? I’m grasping at straws.
Therabee

Therabee is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 18, 2023 and August 18, 2023. The archive places it in contexts such as "fly into the container labelled ‘Therabee’". It most often appears alongside Anil Seth, Astralcodexten Com, Being You.

Reference entry
Therabee
Mention count
1
Issue count
1
First seen
August 18, 2023
Last seen
August 18, 2023
August 18, 2023 · Original source
If they want it, they’re likely a happy-go-lucky bee with nothing on their mind. If you simulate the bee being attacked by a predator right before this test, they are much less likely to fly to the solution and much more likely to fly into the container labelled ‘Therabee’.
Thomas the Tank Engine

Thomas the Tank Engine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "no word yet on Thomas the Tank Engine". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
Thomas the Tank Engine
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
Thorne

Thorne is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 05, 2022 and October 05, 2022. The archive places it in contexts such as "every single brand we have tested so far has had at least one thing fail, save for Thorne"; "I trust Nootropics Depot, Thorne, NOW, and Jarrow". It most often appears alongside AIDP, Alkemist, Amazon.

Reference entry
Thorne
Mention count
1
Issue count
1
First seen
October 05, 2022
Last seen
October 05, 2022
October 05, 2022 · Original source
NOW has their own in-house lab, and they have been trying to clean up the standards of the industry for a while. We have had a couple things of theirs fail, but only for content lower than label claim, not fake or impure or anything like that. So while I wouldn't say trust everything from them 100%, NOW is one of the better ones in this industry seemingly trying to make things better. I also have more trust for Thorne than most […] every single brand we have tested so far has had at least one thing fail, save for Thorne. Some of the brands have almost everything fail. Others like Life Extension, Jarrow, and NOW have most things pass with only some failing. It's a crap shoot.
Botanicals are more complicated. Commonly-used botanicals from reputable brands are usually about as trustworthy as vitamins, but there are lots of complications around extraction processes and sometimes you might get 50% more or less than you thought. Less-commonly-used botanicals are less clear; you still will rarely find outright sugar pills, but you may find people bungling the chemistry, not caring too much about exact amounts, or selling mushroom mycelium instead of fruiting body. “Male enhancement” products are their own special class of danger zone, as are anything that’s been featured on The Joe Rogan Experience; you should be extra careful to buy from only the most reputable companies. I trust Nootropics Depot, Thorne, NOW, and Jarrow, in that order, but you’ll want to do your own research and maybe check ConsumerLab for the particular product you’re buying.
Tindr

Tindr is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 03, 2024 and September 03, 2024. The archive places it in contexts such as "Tindr. Hinge. Grindr". It most often appears alongside 1980s, Air Force One, anal probing.

Reference entry
Tindr
Mention count
1
Issue count
1
First seen
September 03, 2024
Last seen
September 03, 2024
September 03, 2024 · Original source
“Maybe not at Thiel Capital. But go outside, and you’ll find that people are, in fact, having sex all the time. Tindr. Hinge. Grindr. Young people are going out and having casual sex every weekend. There are fourteen different BDSM sex clubs in San Francisco alone. If you look at the modal society throughout history, they’re forbidding their women from leaving the house, or holding them to such high modesty standards that showing a bare ankle would be a scandal. They’re locking people up for owning porn, or killing them for being gay, or calling them rakes or sluts for having sex outside of marriage. Meanwhile, in our society women go everywhere in skimpy skin-tight clothing, you can f@&k a different partner every week, you can be polyamorous or transgender. I read conservative writers saying that no society like ours can survive over the long term. But I’ve thought about it longer than they have, and I think no society like ours could ever come to exist at all. That’s because it’s not a real society. It’s somebody’s weird fetish free-use-adjacent fantasy.”
Tinkertoys

Tinkertoys is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 05, 2026 and February 05, 2026. The archive places it in contexts such as "connect Legos, Tinkertoys, Lincoln Logs, etc". It most often appears alongside 4o, 60 Minutes, @MattZeitlin.

Reference entry
Tinkertoys
Mention count
1
Issue count
1
First seen
February 05, 2026
Last seen
February 05, 2026
February 05, 2026 · Original source
41: The unfortunately-acronymed Free Universal Construction Kit is “a collection of open source 3D-printable adapters that [enables] interoperability between ten popular children's construction toys”, ie connect Legos, Tinkertoys, Lincoln Logs, etc.
Ton Shen Health

Ton Shen Health is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 26, 2022 and October 26, 2022. The archive places it in contexts such as "When I Google various permutations of “supplement dangerous lead level”, all the examples I can find of this happening in the US are still about this one case from a supplement company I’ve never heard of in 2016. In fact, what is Ton Shen Health / Life Rising, the company implicated in this?". It most often appears alongside American ginseng, apple juice, Ashwagandha.

Reference entry
Ton Shen Health
Mention count
1
Issue count
1
First seen
October 26, 2022
Last seen
October 26, 2022
October 26, 2022 · Original source
In fact, what is Ton Shen Health / Life Rising, the company implicated in this? I’m having trouble figuring this out - when I look it up, it looks like a small chain of acupuncture clinics in Chicago run by “Herbal Master Zhengang Guo”, which is still operating (!) and still selling supplements (!) But the FDA seized 300,000 bottles - how did this one guy produce produce so many supplements? All we have from the FDA, statement is that the supplements recalled “were mostly sold locally in Chicago area in retails stores [sic] and some were distributed to other states through mail orders”.
Toucan

Toucan is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one"; "Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
Toucan
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
Toucan https://chrome.google.com/webstore/detail/toucan-by-babbel-language/lokjgaehpcnlmkebpmjiofccpklbmoci is one. There are a few different ones out there.
TPU

TPU is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 01, 2022 and April 01, 2022. The archive places it in contexts such as "But Newton and Einstein didn’t have TPUs". It most often appears alongside Bayes, chromatic number, Contra Hoel.

Reference entry
TPU
Mention count
1
Issue count
1
First seen
April 01, 2022
Last seen
April 01, 2022
April 01, 2022 · Original source
In Contra Hoel, I talked about machine learning as feeling different from some other scientific fields: there are frequent exciting new discoveries. This shouldn’t be surprising. Physics is stagnant because Newton and Einstein already got all the cool results. But Newton and Einstein didn’t have TPUs so they couldn’t discover things about machine learning.
Tranylcypromine

Tranylcypromine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "Tranylcypromine is a MAO inhibitor, an unusual older class of antidepressant". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
Tranylcypromine
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Tranylcypromine is a MAO inhibitor, an unusual older class of antidepressant. These are very effective and tend to work even in otherwise treatment-resistant patients. But they have potentially serious interactions with many foods and medications, and you have to be very careful to avoid these while taking them (for example, you can’t eat many types of cheese). Many psychiatrists refuse to prescribe this medication because they are cowards, and I don’t have a good solution to this.
trazodone

trazodone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 22, 2021 and December 22, 2021. The archive places it in contexts such as "probably using trazodone, the #2 most popular sleeping pill in the US". It most often appears alongside aspirin, Astralcodexten Com, budesonide.

Reference entry
trazodone
Mention count
1
Issue count
1
First seen
December 22, 2021
Last seen
December 22, 2021
December 22, 2021 · Original source
Or maybe you’re afraid of lawsuits. If you get sued for malpractice, it’s nice to be able to tell the jury “it says this drug is okay for this condition right on the label”. But this doesn’t usually stop doctors from doing off-label prescriptions. Gabapentin is the 18th most-prescribed drug in the US, almost always for nerve pain or anxiety, but its label only officially endorses use for seizures or shingles. Beta-blockers for social anxiety? Off-label and dirt common. Prazosin for PTSD nightmares? Off-label and dirt-common. How do doctors sleep at night, knowing they’re constantly at risk of getting sued for off-label prescriptions? Probably using trazodone, the #2 most popular sleeping pill in the US, whose label says it should only be used for depression. No, seriously, it’s because most doctors don’t even know these indications are off-label, plus their medical school professors all did it too so it doesn’t feel transgressive.
trontinemab

trontinemab is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 14, 2025 and August 14, 2025. The archive places it in contexts such as "a blood brain barrier (BBB)-penetrating antibody such as trontinemab". It most often appears alongside A. Bejanin, A. de Calignon, A. Elobeid.

Reference entry
trontinemab
Mention count
1
Issue count
1
First seen
August 14, 2025
Last seen
August 14, 2025
August 14, 2025 · Original source
I am not claiming that the disease is “as simple as” amyloid deposits directly inducing neurodegeneration. As described above, they act indirectly, via the eventual downstream tau pathology, and possibly an associated microglial/astrocytic inflammatory response. Therefore, there are many people in the preclinical, amyloid-only disease phase who will eventually progress to dementia but have not yet. These two clarifications imply that even though amyloid pathology is a necessary and (in enough severity) sufficient cause of the disease under normal circumstances, therapies with other targets might still be effective, either intervening upstream such that amyloid deposits never occur, or downstream so as to prevent the neurodegenerative process. The testable prediction I would bet on the following: A therapy whose sole intended mechanism involves amyloid production or clearance, in a randomized, double-blind, placebo-controlled trial, will, in the next 12 years, achieve a slowdown of cognitive decline of at least 75%, with a p-value below 0.001, in its preregistered primary cognitive endpoint (or an average of all such endpoints if more than one exists). I’d eventually expect better than 75% efficacy, but getting stuff to work takes time, and I wanted to make a prediction which can be tested in a reasonable timeframe. On the other hand, if a clinical trial completes earlier than 12 years from now (perhaps [73], reading out in 2027), sustains extremely good amyloid clearance at the preclinical stage, and has a good safety profile, but doesn’t make substantial progress towards this 75% goal, then I would consider this prediction refuted in advance. For targeting amyloid, I’m most optimistic about a blood brain barrier (BBB)-penetrating antibody such as trontinemab [74–76], but with an epitope more like lecanemab’s, and given in the preclinical disease stage. Other options for targeting amyloid include antisense oligonucleotides for APP as well as γ-secretase modulators. The successes and failures of amyloid antibodies There have now been three amyloid antibodies with positive phase 3 (and earlier) clinical trials on cognitive endpoints (but with much less than 75% efficacy): Aducanumab in phase 1b [77] (19% on my average across cognitive endpoints for the highest two doses) and one of two phase 3 trials [78] (22%, but negative 2% in the other trial, which also gave a lower dose on average).
[74] J. Shugart, “Trontinemab data strengthen hope for brain shuttles,” Alzforum News, 2024, Available: https://www.alzforum.org/news/conference-coverage/trontinemab-data-strengthen-hope-brain-shuttles
[75] L. Kulic et al., “Latest interim results from the Brainshuttle AD study: A phase Ib/IIa study of trontinemab in people with Alzheimer’s disease.” Poster presented at the Clinical Trials on Alzheimer’s Disease (CTAD 2024), Madrid, Spain, Oct. 30, 2024. Available: https://medically.roche.com/content/dam/pdmahub/restricted/neurology/ctad-2024/CTAD-2024-presentation-kulic-latest-interim-results-from-brainshuttle-ad-study.pdf
TTE

TTE is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 19, 2022 and October 19, 2022. The archive places it in contexts such as "Yo! TTE is down to 43". It most often appears alongside AI Circle, Anna, Bay Area.

Reference entry
TTE
Mention count
1
Issue count
1
First seen
October 19, 2022
Last seen
October 19, 2022
October 19, 2022 · Original source
Yo! TTE is down to 43 Sounds good to me! But it ain’t ESG. Wanna tell Blackrock to suck my cock But if they fuck us over we can't sell the stock So here's what we do - fudge the CO2 You think that that pinko Fink will have a fucking clue? We'll feed them lies, keep our eyes on the prize And our ESG will stand for Eat Shit, Guys.
Turkplex

Turkplex is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 27, 2025 and February 27, 2025. The archive places it in contexts such as "Gorilla Mind is testing their products, like Turkplex". It most often appears alongside /r/NootropicsDepot, @fae_dreams, @ObhishekSaha.

Reference entry
Turkplex
Mention count
1
Issue count
1
First seen
February 27, 2025
Last seen
February 27, 2025
February 27, 2025 · Original source
Some blueprint products seem to be clearly out of spec, so Mr. Johnson probably doesn't really know what he's doing either. Not to mention that the lab they seem to be using, Certified Labs, used to be ABC testing which we know have botched a bunch of testing in the past. So bad in fact, that the FDA even intervened. It's always funny that quite a few brands with problematic products all seem to do their testing via Certified Labs/ABC testing. For example, look at where Gorilla Mind is testing their products, like Turkplex, which recently failed miserably in our testing. Bryan Johnson boasts about having all the money in the world, and that he's so super advanced blah blah blah, but he's testing with a seemingly sketchy lab even though there are a plethora of very well known labs doing great work, like Alkemist Labs for example. It really makes me wonder if these guys are knowingly selecting Certified Labs/ABC testing for a specific reason, or perhaps Certified Labs is very aggressive in marketing and if you are new in the industry, they may be the first lab you find? Odd, but could be a possibility.
Twinder

Twinder is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 14, 2023 and February 14, 2023. The archive places it in contexts such as "There’s something called Twinder for Twitter which seems to do this correctly". It most often appears alongside Aella, Austin, clown dating site.

Reference entry
Twinder
Mention count
1
Issue count
1
First seen
February 14, 2023
Last seen
February 14, 2023
  • 23 February 14, 2023
February 14, 2023 · Original source
One solution is to piggyback off existing social media sites. There’s something called Twinder for Twitter which seems to do this correctly, though they haven’t made any posts since 2018 and I think they’re defunct. Also Facebook Dating, although it’s (indefensibly) not available on computers and has to be accessed by cell phone. But these aren’t real piggybacks; just because your crush has a Twitter account doesn’t mean they use Twinder. Facebook Dating makes the interesting decision to, if you register a crush on someone, send them a Facebook message saying that an anonymous person likes them and they should try getting Facebook Dating; I can’t decide whether this is a necessary evil, or if it violates the principle of not imposing emotional costs on people who don’t want them.
Uber Eats

Uber Eats is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 11, 2024 and January 11, 2024. The archive places it in contexts such as "sells them in an Instacart or Uber Eats like model". It most often appears alongside ACX Grants, Africa, Amalgamated Kenyan Wells.

Reference entry
Uber Eats
Mention count
1
Issue count
1
First seen
January 11, 2024
Last seen
January 11, 2024
January 11, 2024 · Original source
To give you a simple example, Foodhini is a for profit company that takes various refugees and has them make their regional cuisines then sells them in an Instacart or Uber Eats like model. It's a profitable company but it also does significant work to help these people get on their feet. Whether that's services to make sure the work is legal or helping them set up restaurants (which in turn profits Foodhini in various ways).
Ubers

Ubers is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 20, 2023 and February 20, 2023. The archive places it in contexts such as "taking Ubers". It most often appears alongside 2020 election, 2020 primary, 23andme.

Reference entry
Ubers
Mention count
1
Issue count
1
First seen
February 20, 2023
Last seen
February 20, 2023
February 20, 2023 · Original source
First World economies will increasingly be marked by an Officialness Divide. Rich people, the government, and corporations will use formal, well-regulated, traditional institutions. Poor people (and to an increasing degree middle-class people) will use informal gig economies supported by Silicon Valley companies whose main skill is staying a step ahead of regulators. Think business travelers staying at the Hilton and riding taxis, vs. low-prospect twenty-somethings staying at Air BnBs and taking Ubers. As Obamacare collapses, health insurance will start turning into one of the formal, well-regulated, traditional institutions limited to college grads with good job prospects. What the unofficial version of health care will be remains to be seen. If past eras have been Stone Age, Bronze Age, Iron Age, Information Age, etc, the future may be the Ability-To-Circumvent-Regulations Age.
I don’t think the Officialness Divide or the Ability-To-Circumvent-Regulations Age arrived in any meaningful way. I think I was riding high off the age of Uber and Bitcoin, and expected people to continue to have that level of creative/entrepreneurial spirit, and instead, they didn’t.
Gary Marcus can still figure out at least three semi-normal (ie not SolidGoldMagikarp style) situations where the most advanced language AIs make ridiculous errors that a human teenager wouldn’t make, more than half the time they’re asked the questions: 30% ACTION TRANSFORMERS: Maybe the next big thing. This is where you can give a language model an Internet connection, tell it something like "respond to all my emails" or "order some cheap Chinese food that looks good off UberEats, my credit card number is XXXXX", and it will do it. I think this technology will be ready in the next five years, although it might suffer from the self-driving car problem where you need more nines of reliability than it can provide. You want to be really sure it won't respond to an email from your boss by telling her to f@#k off, or buy a Chinese restaurant instead of food from a Chinese restaurant. I think it will start as an assistant that will run all of its decisions by you, then gradually expand out from there. AI can play arbitrary computer games at human level. I will count this as successful if an off-the-shelf AI, given a random computer game and some kind of API that lets it to against itself however many times it wants, can reach the performance of a mediocre human. The human programmers can fiddle with it to make it compatible with that particular game’s API, but this is expected to take a few days of work and not involve redesigning the AI from scratch: 25%
UberShare

UberShare is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2024 and October 24, 2024. The archive places it in contexts such as "The UberShare carpool program hasn’t taken off". It most often appears alongside 1960: The Year The Singularity Was Cancelled, 1960s, 1973.

Reference entry
UberShare
Mention count
1
Issue count
1
First seen
October 24, 2024
Last seen
October 24, 2024
October 24, 2024 · Original source
The most interesting new claim I heard was that self-driving cars could help the environment by encouraging carpools. The UberShare carpool program hasn’t taken off, but that’s mostly because people are reluctant to share a car with a stranger. Self-driving cars have more design flexibility, and you might be able to turn them into a series of private pods. You could sit in your own private pod while your robotaxi made a two-block detour to pick up a second passenger.
uBlock

uBlock is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 12, 2024 and September 12, 2024. The archive places it in contexts such as "how to banish it using uBlock". It most often appears alongside @halomancer1, ACX, Amazon.

Reference entry
uBlock
Mention count
1
Issue count
1
First seen
September 12, 2024
Last seen
September 12, 2024
September 12, 2024 · Original source
36: Amazon has added an incredibly annoying popup thing called “Rufus” that appears on every page now and can’t be turned off (Jeff Bezos would be turning in his grave). If you can’t figure out a good non-Amazon way to get the products you need, here’s a good description of how to banish it using uBlock.
UJLIBLÖK

UJLIBLÖK is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 04, 2021 and October 04, 2021. The archive places it in contexts such as "they end up getting minimalist Scandinavian furniture with names like UJLIBLÖK". It most often appears alongside 19th century African art, 20th century, 9-11.

Reference entry
UJLIBLÖK
Mention count
1
Issue count
1
First seen
October 04, 2021
Last seen
October 04, 2021
October 04, 2021 · Original source
As far as I can tell, you can’t buy any of these anywhere - they’re a combination of antiques and concept pieces. The people who pin these and pine after these end up getting minimalist Scandinavian furniture with names like UJLIBLÖK, just like everyone else.
Umanity

Umanity is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 12, 2021 and February 12, 2021. The archive places it in contexts such as "Umanity uses a revolutionary proof-of-work algorithm based on CAPTCHAs". It most often appears alongside BuffyCoin, CAPTCHA, Catholic Church.

Reference entry
Umanity
Mention count
1
Issue count
1
First seen
February 12, 2021
Last seen
February 12, 2021
February 12, 2021 · Original source
Umanity: Computers keep taking our jobs; what if we turned the tables on them? Umanity uses a revolutionary proof-of-work algorithm based on CAPTCHAs. Each node generates a few letters of a CAPTCHA, then transmits it as a bitmap to other nodes, until they arrive at a full CAPTCHA by consensus without any of them knowing the whole answer. Once a human answers the CAPTCHA, each node cryptographically signs off on its own contribution until they agree the CAPTCHA is solved and issue an Uman to the solver. Instead of guzzling electricity and contributing to climate change, mining Umanity provides steady well-paying jobs to underskilled workers.
Banned because: Courts rejected Umanity's arguments that its workers were independent contractors and made it reclassify them as employees; nobody could figure out how to decentralizedly give people paid time off and maternity leave.
USDCoins

USDCoins is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 08, 2021 and February 08, 2021. The archive places it in contexts such as "You need USDCoins, a stablecoin related to Ethereum". It most often appears alongside AlphaGo, Civil War, Coinbase.

Reference entry
USDCoins
Mention count
1
Issue count
1
First seen
February 08, 2021
Last seen
February 08, 2021
  • 21 February 08, 2021
February 08, 2021 · Original source
Probably it's the second one. I tried to bet against Trump, but getting money into the market was pretty hard. You need USDCoins, a stablecoin related to Ethereum. Polymarket tries to let you buy them directly, but their app wanted me to give them a security code which never showed up, so I gave up on this. Instead I bought some USDC at Coinbase and tried to send them over. But along with the usual Ethereum gas fees, they have something called a relayer, which is supposed to collect my money and put it in my account. And it's apparently heavily backed up, and after two days my money is nowhere to be seen (though I believe them when they say that they're trying their hardest and it will probably percolate through the Ethereum network someday). Maybe everyone's having these kinds of issues and this is why the Trump contract hasn't adjusted? I'm not sure. I will keep you updated if my money ever materializes.
V100 GPU

V100 GPU is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 23, 2026 and February 23, 2026. The archive places it in contexts such as "the FLOP/watt efficiency of a V100 GPU". It most often appears alongside ACX, Bay Area, Bio Anchors.

Reference entry
V100 GPU
Mention count
1
Issue count
1
First seen
February 23, 2026
Last seen
February 23, 2026
February 23, 2026 · Original source
Cotra estimated “~2.5 OOM worse [than the brain], +/- 1 OOM”, based on reference points like how much less efficient dialysis machines are than a human kidney, how much more efficient solar panels are than leaves, and the FLOP/watt efficiency of a V100 GPU. But most of those anchors had little to do with where ML algorithms were in 2020 when bioanchors was written, and would have given a very similar estimate for “present state of ML algorithms” 20 years earlier or 20 years later.
Valium

Valium is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 08, 2022 and March 08, 2022. The archive places it in contexts such as "benzodiazepines, a popular class of psychiatric medication including ... Valium (diazepam)". It most often appears alongside alcohol, allopregnanolone, allopregnanolone.

Reference entry
Valium
Mention count
1
Issue count
1
First seen
March 08, 2022
Last seen
March 08, 2022
March 08, 2022 · Original source
(source) GABA is the main inhibitory neurotransmitter; it’s usually associated with relaxation and sedation. A positive allosteric modulator is a chemical that makes receptors respond more strongly to their targets. So “a positive allosteric modulator of GABA” means a chemical that makes the brain respond stronger to relaxation/sedation signals. Sounds pretty useful! You may do some positive allosteric modulation of GABA yourself sometimes; this is one of the major actions of alcohol. Also of the benzodiazepines, a popular class of psychiatric medication including Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam). The “-pam” at the end stands for positive allosteric modulator! (or maybe that’s just an urban legend, I’ve never found proof either way) The discovery of endorphins (ie endogenous opiates) helped shed light on the brain’s reward system. So the discovery of a sort of endogenous benzodiazepine was pretty exciting. Maybe it’s some kind of master control switch for anxiety or something? Psychiatrists only know two ways to respond to an exciting new thing: publishing breathless studies claiming that it’s the true mechanism of action for SSRIs, and publishing breathless studies claiming that it’s the true biological basis of depression. This time, they did both: see eg Fluoxetine elevates allopregnanolone levels in female rat brain and The role of allopregnanolone in depressive-like behaviors. The basic theory was that stress / social isolation / etc → decreased allopregnanolone → something something BDNF and synaptogenesis → depression. And SSRIs → increased allopregnanolone → something something BDNF and synpatogenesis → recovery! Change the word “allopregnanolone”, and that’s every theory in psychiatry. But this particular theory had two extra pieces of evidence: premenstrual dysphoric disorder and postpartum depression. Remember, allopregananolone is a natural metabolite of the female hormone progesterone. Progesterone levels go up during pregnancy and the ~18th day of the menstrual cycle, then crash back down after delivery and the ~24th day of the menstrual cycle. Meanwhile, some women get depressed after delivering a baby, or on the ~24th day of their menstrual cycle. Suspicious! Maybe it’s because their progesterone was getting converted into allopregnanolone, an antidepressant hormone that affects mood! (why doesn’t every woman get PPD and PMDD? This study suggests that women with PMDD have altered sensitivity to allopregnanolone; plausibly people with PPD have some other form of altered sensitivity. In case you have the same question I do: the correlation between PMDD and PPD is not 100% but still pretty significant) History of allopregnanolone research (source) The next step was to see if making patients take allopregnanolone can treat these conditions. This is kind of hard, because allopregnanolone is a tough chemical to get into people’s bodies; the traditional method involves sticking an IV into someone and infusing it slowly over several days, and it has to be done in a hospital. Still, Kanes et al tried this in 2017. The study was open-label (ie no placebo) and very small (only four women) but appeared to work extraordinarily well. Four post-partum women who qualified as “severely depressed” when they started the infusion progressed to “completely recovered” within twelve hours. Nothing else except maybe ketamine had produced results like this before. 3: What studies were done on Zulresso? This followup study by Kanes was the first real RCT, although it only had 21 patients. In accordance with the venerable First Study Ever tradition, it found really large positive effects on post-partum depression. That encouraged Sage Therapeutics to fund a bigger Phase 3 trial, Meltzer-Brody (2018). In accordance with venerable Bigger Phase 3 Trial tradition, its results weren’t quite as good as the First Study Ever. But they were still pretty good: Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Notice that lower doses worked better than higher doses. This is sometimes a red flag on a study. But this time it seems legit; see “Biphasic Actions At The GABA-A Receptor” here for an explanation. Both studies also evaluated side effects. These were generally mild, but two people (about 2% of the study population) lost consciousness. Nothing seemed wrong with them, and researchers mostly attributed this to allopregnanolone being a sedating drug. If you sedate people too hard, they pass out. Faced with these results, the FDA approved allopregnanolone for post-partum depression, but subjected it to a REMS (Risk Evaluation And Mitigation Strategy) - basically, doctors who want to prescribe it will need to take special courses and do extra paperwork. This kind of surprised me - there are plenty of sedating drugs that make you pass out in overdose. Also, since patients will be getting it IV, there will probably be a nurse around to check if they passed out and take appropriate actions if so. But the FDA really likes putting restrictions on things, and I guess this was a free chance for them to do that. 4: Is Zulresso freely available at a doctor’s office near me? It’s possible to get Zulresso, but really hard. Because Zulresso is an IV infusion lasting four days, you need to spend four days somewhere that people can put an IV into you and monitor it. Realistically that means a hospital or some other big medical institution. So this is only available for inpatients. Because of the REMS (extra certification and paperwork), most hospitals aren’t interested. You can find a list of ones that are here - it looks like there are about 89 locations in the US with the right certification. Last but not least, a four-day course of Zulresso costs $35,000 for the medication itself, plus much more for the four-day hospitalization it takes to receive it. As usual, insurances will cover it iff you can document you’ve tried lots of other stuff first. 5: Hold on, does it really cost $35,000? Oho, I see you’ve played the “pharma price analysis” game before. But this time I think the price might actually be defensible. Chemical supply companies (1, 2, 3) generally sell allopregnanolone for $10,000 to $20,000 a gram. (I found one company with a much lower price, but I’m suspicious and am going to dismiss them as an outlier). The usual dose of allopregnanolone is 60 ug/kg/hour x 60 hours, which for a 60 kg person comes out to a total of 0.25g total. Getting that amount from the chemistry supply store would cost about $2,500 - 5,000. I assume pharma-grade allopregnanolone is more expensive than chemistry-store-grade, so it wouldn’t surprise me if a price in the low five-figures was justified by manufacturing alone. Isn’t it still a pretty good deal to find an endogenous neurosteroid, do one or two studies confirming it’s great, produce it for the low five figures, then sell it for the mid five figures? I think maybe not. This drug has a terrible value proposition. Post-partum depression is one of the rarer psych conditions. Most people with PPD won’t check into a hospital and pay $35,000 for a drug infusion. And the people who do will get the drug infusion, feel better, and never need it again (at least until they have another kid) - unlike SSRIs where you can keep charging for monthly prescriptions forever. Sage Therapeutics, the pharma company that owns the patent on Zulresso (and nothing else - this is their only drug!) has done terribly. Their stock is in the doldrums, they almost went bankrupt, and they survived only with the help of a cash infusion by a bigger pharma company. I think this confirms a general trend where at least some expensive medications are pricey because of fundamentals (including regulatory fundamentals) and not just pharma companies making obscene profits. 6: Hold on, how is allopregnanolone different from benzodiazepines? Remember, allopregnanolone is a positive allosteric modulator of GABA, much like benzodiazepines such as Xanax. But Xanax is cheap ($10 for 30 pills). And you can get it at any local pharmacy (plus sometimes on street corners). What’s so special about allopregnanolone that you should pay $35,000 and go into the hospital to get it? The official answer is “allopregnanolone modulates GABA differently from benzodiazepines”. For example, this paper says that: Allopregnanolone allosteric modulation of the action of GABA at GABA-A receptors is much less selective than that of benzodiazepines, which are relatively inactive at α4- or α6-containing GABA-A receptors. If you really like details about receptor subunits, this paper presents the full case. The skeptic’s answer is “who knows?” Psych drugs often work for reasons totally different than we thought. People thought tianeptine was an SSRE for years, until it turned out to be a mild opioid. People thought ketamine was NMDA-ergic for years, until it turned out to be [fill this part in 10 years from now]. Last year a bunch of very smart people tried to claim that SSRI effects had nothing to do with serotonin (I think they were wrong). Just because some guy found that Zulresso acts as a GABA-PAM in some test tube doesn’t mean that’s what’s having any of the relevant antidepressant effects. The troll’s answer is “who says it’s different?” Do benzodiazepines treat depression? Depends who you ask. If you ask benzodiazepine users, their answer is “yes, definitely”. If you ask drug warriors, their answer is “Addictive Substances May Make You Temporarily Feel Good, But They Are Not A Responsible Treatment Option”. If you ask the research literature, it gives vague indeterminate answers, as always. But nobody has ever said benzodiazepines instantly and miraculously cure depression, so how come allopregnanolone seems to do that? A true troll would point out that we probably give allopregnanolone at much higher doses - 2% of allopregnanolone patients were sedated so hard they lost consciousness, whereas this is exactly the sort of side effect I try to avoid when calculating benzodiazepine doses. Maybe if you gave postpartum women an infusion of 300 mg Valium, and maximized your placebo effect by calling it the hot new thing, they’d do pretty well too (several days later, after recovering consciousness). I think the troll answer would be hilarious but I don’t really want to defend it as correct; if I had to bet I’d say the official explanation is the right one. 7: Hold on, why can’t we just give people progesterone and let them metabolize it into allopregnanolone? This turned out to be an interesting enough rabbit hole that I’m going to spin it off into another post later this week. 8: Hold on, people have lots of allopregnanolone when they’re pregnant, right? And then post-partum depression happens when they give birth, and their allopregnanolone level drops. So if you give someone an infusion of allopregnanolone, and then take them off it, that’s a hormonal simulation of giving birth, ie the same thing that caused the problem in the first place? How is that good? Oh, you think you’re clever, do you? What you failed to consider is . . . I didn’t end that sentence because I can’t find anything in the literature addressing this question. But the difference might be that the infusion schedule ramps up gradually, peaks, and then ramps down gradually, which is more of a soft taper than the sudden crash of birth. If anyone knows more about this, please let me know. [EDIT: see this comment] 9: Is allopregnanolone addictive? No, because good luck getting addicted to a $35,000-per-dose chemical. We should probably expect allopregnanolone to be addictive, by analogy to other GABA-PAMs like benzodiazepines and alcohol. But nobody has ever received more than a single dose. You don’t get addicted to benzos after a single pill, or alcohol after a single beer, so in practice AFAIK nobody has ever gotten addicted to this. Or who knows, maybe it’s not addictive. Remember, allopregnanolone is naturally elevated during pregnancy; pregnancy isn’t addictive. And some scientists claim the brain endogenously uses allopregnanolone as a master regulator of depression and anxiety. In theory, if you could give yourself the same amount a non-anxious person’s brain gives them all the time, shouldn’t you be no worse off than that non-anxious person? I don’t know, and remember that your brain also has a lot of endogenous opioids; doesn’t make the exogenous kind any safer. The Drug Enforcement Administration has made Zulresso a Schedule IV controlled substance, which means they’re putting a few very weak restrictions on it but not worrying too much. 10: Does allopregnanolone work for depression that isn’t post-partum? If all psychiatric disorders are secretly allopregnanolone imbalances, then you might expect it to work on all depressions, not just post-partum. I’m sure pharmaceutical executives with dollar signs instead of pupils in their eyes have had this same thought, but I can’t find studies about it. Some of the same people behind the postpartum studies did a very small, very weak study on ganaloxone (a close allopregnanolone relative) for persistent depression; it seemed to work, but also caused a lot of sedation (more than in the postpartum trials? Hard to tell). Nobody’s looked into this further since then, maybe because that was around when the pharma companies realized that the 4-day hospital stay and $35,000 price tag made allopregnanolone a financial loser. The evidence from zuranolone (see below) suggests that allopregnanolone might not work very well against regular depression. 11: What is zuranolone? Wikipedia describes zuranolone as “a swirling, black vortex revered by the Mutsune Native Americans as a dire death god . . . also worshiped by mysterious servitors known as the Hidden Ones.” No! Sorry again! That’s Zushakon, another Great Old One. Zuranolone is Sage Therapeutics’ attempt to turn allopregnanolone into an accessible medication that might actually make them real money. Zuranolone is mostly just allopregnanolone with some extra stuff attached that changes the absorption. Zuranolone can be taken orally, so you don’t have to go to a hospital for four days to receive it IV. It’s potentially less likely to cause loss of consciousness and other undesirable side effects. And it’s under investigation as a potential treatment for postpartum depression, bipolar depression, regular depression, insomnia, and various movement disorders. (that might seem excessive, but benzodiazepines treat a lot of stuff, and if these neurosteroids are kind of like super-benzodiazepines, then this level of optimism might be warranted.) 12: Does zuranolone work? Sage Therapeutics answered this question the same way pharma companies answer every question: with a bunch of studies whose names form overly-cute acronyms. We’ll talk here about ROBIN, WATERFALL, MOUNTAIN, and CORAL - though I assure you there are others. ROBIN tested efficacy in postpartum depression. Results were positive and relatively impressive, about the same as the weaker allopregnanolone studies. WATERFALL, MOUNTAIN, and CORAL tested results in regular depression. WATERFALL was positive but weak. MOUNTAIN was negative. That scared the pharma company and they hacked CORAL to be more likely to give positive results. It did give positive results, but the FDA reads the same biotech magazines I do and knows perfectly well what they did, so I don’t know what Sage expects to gain from this. Overall these trials were disappointing. I think the most likely story is that allopregnanolone = zuranolone, both are moderately effective in postpartum depression, and both have much less efficacy in regular depression, probably not literally zero but also not enough to be worthwhile antidepressants (especially considering cost). Might zuranolone be an excellent anti-anxiety medication? You’d think so - it should be at least as good as benzodiazepines, which are excellent anti-anxiety medications. And researchers seem excited about allopregnanolone as a master regulator of brain anxiety. But the studies aren’t promising. ROBIN and WATERFALL incidentally assessed anxiety; ROBIN found good results in its postpartum population, but WATERFALL found poor-to-mediocre results in its regular population. Studies are hard, and sometimes even really effective drugs can have trouble showing strong results. But these aren’t encouraging. 13: So where do we go from here? Getting FDA approval for zuranolone for postpartum depression seems reasonable; it’ll probably be cheaper and easier than making people go to the hospital to get allopregnanolone. I’m uncertain about the financials of this for Sage, but since they did the study they hopefully think it’s worth it. Otherwise, I’m not sure. It would have been great if zuranolone had shown robust efficacy against regular depression and anxiety, but this is exactly the kind of great thing that never happens in psychopharmacology (motto: “Disappointing Doctors And Patients Since 1982”). It might be worth throwing it against anxiety disorders and PTSD to see if anything sticks, but I wouldn’t bet on it. The research into allopregnanolone as master regulator of brain anxiety states is fascinating, but as far as I know it hasn’t reckoned with the failure of zuranolone to really treat much anxiety. The cynical part of me predicts that once pharma’s done making money off neurosteroids then all of this will die down, and something else that pharma can make more money from will become the master regulator of everything. I expect that the main thing we get out of all this is somewhat better post-partum depression treatment, which might or might not ever become accessible for ordinary people. 14: Predictions In the next five years… Zuranolone gets FDA approval for major depression: 15%
Veldt

Veldt is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 21, 2023 and July 21, 2023. The archive places it in contexts such as "…Jo presumably believes Veldt is worth around 53.75". It most often appears alongside 2008 Financial Crisis, 2023 book review contest, 30-Year Mortgage.

Reference entry
Veldt
Mention count
1
Issue count
1
First seen
July 21, 2023
Last seen
July 21, 2023
July 21, 2023 · Original source
We need a framework for thinking about these trades. Lebron’s first law states that we must know ourselves and our motivations for trading before we trade. We tell ourselves many stories, but someone with intellectual honesty – the person with the most alignment between their motivations and actions – will take money from the person who didn’t go through the work to understand their own motivations. There is a reason that Citadel and other hedge funds pay millions of dollars to trade with retail. They know why they are trading: to maximize profit. And the dilettante who “trades for fun” will be eaten alive by a firm with a much better model of a) the world and b) the dilettante themself. Why did I write this book review? To test my intellectual mettle. I could easily have posted this book review elsewhere, but no, I wanted to see how I stack up against other ACX Book Review contest participants. Similarly, this is often the reason people get into trading. One motivation that Lebron explicitly calls out is intellectual validation. You can toil in obscurity for years as an academic. But in trading, there is a quick feedback loop. If your P&L showed $10M last year and the guy sitting next to you showed $8M, you have demonstrated who is “cleverer” and established a clear hierarchy. What lessons here transfer to our daily lives? Like Paul Graham, Lebron encourages us to keep our identities small. He gives the standard decision-making advice to write down your framework and reasoning for why you made a decision at a specific point in time, in order to avoid biases after the fact. This section of the book contained good general advice, but nothing that will be particularly new for the median ACX reader. 2: Adverse Selection You’re never happy with the amount you traded. Now we start to get into the good stuff. Financial markets are an information aggregation mechanism, relying on multiple parties’ beliefs and recursive Bayesian updates of an individual actor’s beliefs based on the beliefs of others2. Market mechanics demonstrate Bayesian beliefs in action. The following quote is quite long, so skip over it if you don’t want to dive deep into the psychology of making a market. I retained it in full because this is quite literally the best description I’ve ever seen of the Bayesian dance between two market makers: “You are a market maker in South African mining companies. Through years of effort and continual improvement, you have built a trading model for the company Veldt Resources. You walk into work one day, ready to set up your trading for the day. It's a stock that doesn't trade much, and usually there are only two market makers: you and another (we'll call her Jo). She's sharp, and she competes well to trade against customer orders that come in. Your model has Veldt valued at 54.35 ZAR (South African rand). You're going to start quoting the stock, so you're about to turn on your machine making a market 54.25 - 54.45 (1000x)3. Before you turn on, you check the current market and notice that Jo has already turned on and she's making her market 53.50 - 54.00 (2000x). If you were to turn on your machine, your market would cross her market, and you would buy 1000 shares from her for 54.00. You now need to make a decision. Whose model do you believe more, yours or Jo's? If you believe yours, you should turn on your machine, trade at 54.00, and expect to make money. If you believe Jo's model, you should adjust your own model parameters to match her market and turn on, making a similar market to hers. What to do? As with many dichotomies, this is a false one. And as with many decision processes, Bayesian reasoning lights the way… …Jo presumably believes Veldt is worth around 53.75 (the average of her bid and offer). But how confident is she in her belief? The width of her market can give you a clue. It's 0.50 ZAR, whereas yours was going to be 0.20 ZAR wide. All other things equal, you should think that Jo only has 40% (0.20/0.50) of the confidence in her fair value as you do in yours. On some absolute scale of confidence, you can say you had a belief-strength of 100 in your fair value of 54.35 (before seeing Jo's market), and Jo has a belief-strength of 40 in her fair value of 53.75 (before seeing yours). And it turns out the weighted average of these two beliefs is quite a reasonable way to combine them: 100/140 * 54.35 + 40/140 * 53.75 = 54.18. Your updated fair value, having seen Jo's market, is thus 54.18 ZAR. This procedure is a quick, heuristic, and reduced version of Bayesian belief-updating, and a good reference on the subject is A.L. Barker's 1995 paper. After updating, you now believe that the stock is worth 54.18. Assuming your trading costs, risk limits, and return requirements are satisfied, buying 1000 shares for 54.00 is a good trade. Naively, you might just put out a 54.00 bid for 1000 shares, trade with half the 2000 share offer, and hope to collect your expected-value ZAR. In practice, however, you might be able to make even more. If Jo is making a 0.50 wide market, maybe she'd be willing to sell lower than 54.00. It's conceivable that if you put out a 53.90 bid for 1000 shares, Jo will sell at that price, and you collect an extra 100 ZAR! Of course, Jo could react differently. She could see your bid and use that information to change her market, in much the same way you did before turning on. These are difficult decisions, ones where experience with the product and the market make a big difference in being able to eke out a little extra edge. Let's play it safe however and pay 54.00 for 1000 shares. You trade, and Jo reacts by immediately canceling her market. This is not an uncommon occurrence in illiquid stocks, especially in emerging markets, so you're not too surprised. You wait a couple of minutes, mentally visualizing Jo in front of her six monitors, evaluating her trade and her model. Finally, she turns back on. Her new market is 53.50 - 54.05 (10000x)! You reason that Jo has seen that someone (you) disagrees with her valuation of the stock. Jo is a good Bayesian like you, and so she has incorporated that information into her model and updated her beliefs about the fair value of the stock. Her updated belief is that she now wants to sell even more stock, at a marginally higher price. Clearly, she almost entirely discounts the information you've communicated to her with your trade. How should you react? It seems fairly clear that, assuming Jo is not a crazy or incompetent market maker (usually a fair assumption), your trade was a bad one. You bought 1000 shares, when in retrospect, you would have wanted to buy much less, probably zero. Imagine instead that Jo had turned back on with a market of 54.00 - 54.50 (1000x). Her reaction now clearly indicates the information you gave her with your trade is valuable, and she has adjusted her beliefs accordingly. Your trade was probably a good one. Don't you wish you had bought all 2000 shares on offer? No matter what Jo's reaction is, you will be unhappy with your trade. Note that Jo will be unhappy too, since retrospectively she should have either made her initial market bigger or smaller. Welcome to the joyous world of trading!” Whether or not you make money, you have regrets! If you profited, you could have made more. If you lost money, you shouldn’t have made the trade at all. Like death and taxes, you can’t avoid adverse selection. Lebron continues to highlight a few areas of trading that have adverse selection problems. First, IPOs. If you buy the stock in an IPO, you expect the share price to “pop” on the first day of trading. However, if others also have this expectation, the round will be oversubscribed. You can only get the quantity of shares that you bid for when the market doesn’t think the shares will go up. So if you are able to get the shares that you want, the IPO is likely a dud. See also: Venture Capital fundraising. Second, powerful entities that change the rules of the game while you’re playing. Exchanges nullify “erroneous” trades. Brokerages limit buying. Anyone who tried to buy GameStop stock on Robinhood on January 28, 2021, knows this form of adverse selection all too well. Lebron also highlights “special trades”, in which you should throw the “normal rules” out of the window. This advice generalizes to other areas of life: “The normal rules do not apply. If you remove yourself from our usual routine, if you think hard and clearly about the specific situation, maybe you can do something good. Perhaps even great. Others will be paralyzed by inaction, but perhaps you won’t be. Crises can be opportunities.” 3: Risk Take only the risks you’re being paid to take. Hedge the others. In trading, as in life, you can make the right call in expected value terms but still lose due to randomness. Some of that randomness is avoidable. Some of it is not — and can be accounted for by hedging. Here, Lebron encourages us to rely on multiple risk measures and actively seek to understand the risks that we might be subject to. That’s all well and good in the world of finance, with derivatives contracts. But how might this apply in other areas of life? If you work for a publicly traded company and are compensated in stock, sell your shares as soon as you receive them. This is not because I don’t expect the share price of Microsoft/Meta/Apple/etc. to go up. The stock may very well outperform the market. But you are not being compensated for the added risk that you take on here. Your employment prospects at Microsoft/Meta/Apple/etc. are highly correlated with the share price. When the share price is down is when layoffs happen. Former Enron employees can chime in here. Similarly, it makes sense to hedge anything that is outside of your control. Let’s say you’ve decided the crypto bear market of 2023 is a great time to start a new crypto company. Your success depends on things within your control, such as: Your idea
venlafaxine

venlafaxine is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 25, 2021 and May 25, 2021. The archive places it in contexts such as "I tend to avoid the other popular SNRI, venlafaxine". It most often appears alongside 2002 meta-analysis by Cochrane Collaboration, 5-HTP, 5-HTP.

Reference entry
venlafaxine
Mention count
1
Issue count
1
First seen
May 25, 2021
Last seen
May 25, 2021
May 25, 2021 · Original source
Duloxetine is an SNRI, which supposedly means it might have some advantages over SSRIs, although studies are not completely clear. It might be better for patients with chronic pain, since it sometimes helps this also. I tend to avoid the other popular SNRI, venlafaxine, because it has very difficult withdrawal and no obvious advantages over duloxetine.
I haven’t really been convinced there’s much role for thyroid hormone or lithium as a main strategy for unipolar depression unless you have some special reason to want to use these (for example, lithium to make someone less suicidal, or thyroid hormone to correct hypothyroidism). Venlafaxine has high withdrawal potential and few obvious advantages over duloxetine. Desvenlafaxine, vilazodone, and vortioxetine are expensive without having obvious advantages over much cheaper drugs, and I can rarely find a use for them. The seligiline patch is more expensive than, and probably worse than, other MAOIs, so I rarely use it.
Vensim

Vensim is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Think Airtable+Vensim+Roam+Kumu". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Vensim
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#6: System Dynamics Simulator I'm Oleksandr Nikitin, and I want to build a system dynamics simulator. Enable independent researchers to simulate, forecast, and visualize metabolic pathways, epidemic spread, mass transit, ecology, macroeconomics, etc. Show, don't tell. Without code. Think Airtable+Vensim+Roam+Kumu, integrated and working offline. Why offline? Why simulate? Why a new tool? Complex systems must be simulated. You miss emergent phenomena if you analyze parts separately or simplify the details. Offline sets you free from distractions and groupthink. Free to make your own breakthroughs. Take your references, notes and data with you, dive deep, then return with the verified, reproducible, interactive model. Research can take years. Tools should outlast devices and app stores. And it must be fast. Isn’t it insane for a productivity tool to make you wait? I spent years on prototypes and algorithms, tested in companies since 2013, and now I want to put these experiments together. Not as a startup. As a tool accessible to everyone. The plan: create a community of curious inquisitive makers, empower them with a small fast and robust core app, iterate and grow together, augment the human intelligence even more, and understand the world. I seek funding to focus on this project full-time, for two years. To launch and to guide people to the finished research. Sounds inspiring? Worth the money? Want more details? Ping me at oleksandr@tvori.info. Also see https://cortex.substack.com/
VERVE-102

VERVE-102 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between July 01, 2025 and July 01, 2025. The archive places it in contexts such as "New treatment may be able to permanently decrease cholesterol 69% after a single shot ... VERVE-102 aims to provide a one-time fix". It most often appears alongside Afrobarometer, AGI, AI 2027.

Reference entry
VERVE-102
Mention count
1
Issue count
1
First seen
July 01, 2025
Last seen
July 01, 2025
July 01, 2025 · Original source
52: New treatment may be able to permanently decrease cholesterol 69% after a single shot. “Instead of managing cholesterol over time like statins, VERVE-102 aims to provide a one-time fix by ‘switching off’ a specific gene, known as PCSK9, in the liver.”
Viagra

Viagra is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 24, 2022 and November 24, 2022. The archive places it in contexts such as "Semaglutide is now as searched-for on Google as ... Viagra"; "Semaglutide is now as searched-for on Google as Prozac or Viagra". It most often appears alongside ACE inhibitors, ACE inhibitors, Adderall.

Reference entry
Viagra
Mention count
1
Issue count
1
First seen
November 24, 2022
Last seen
November 24, 2022
November 24, 2022 · Original source
Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Victoza

Victoza is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 30, 2022 and November 30, 2022. The archive places it in contexts such as "I took victoza (=saxenda, but approved for diabetes)". It most often appears alongside Adam, AMG-133, amoxicillin suspension.

Reference entry
Victoza
Mention count
1
Issue count
1
First seen
November 30, 2022
Last seen
November 30, 2022
November 30, 2022 · Original source
First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use. I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs. I do expect the price to come down relatively quickly due to competition, which is a good thing. Education Realist (blog) writes: I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird. I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily. I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon. I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant. Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno. I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors. Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro Eliezer Yudkowsky writes: I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations. Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same. Lan writes: I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.) Walter Sobchak, Esq writes: I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda. I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem. I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020. I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal. I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years. I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000. I can afford it and it has been worth while. I call it a bargain, the best I've ever had. I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down. My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen. My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Victoza®

Victoza® is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2025 and March 12, 2025. The archive places it in contexts such as "Liraglutide (Victoza®, Saxenda®)". It most often appears alongside Denmark, DOGE, Eli Lilly.

Reference entry
Victoza®
Mention count
1
Issue count
1
First seen
March 12, 2025
Last seen
March 12, 2025
March 12, 2025 · Original source
Liraglutide (Victoza®, Saxenda®)
View Master

View Master is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 16, 2024 and August 16, 2024. The archive places it in contexts such as "View Master and the Magic-8 Ball". It most often appears alongside 20th Century Fox, Abomination, Abomination.

Reference entry
View Master
Mention count
1
Issue count
1
First seen
August 16, 2024
Last seen
August 16, 2024
August 16, 2024 · Original source
Given Marvel Comics, why Silver Age (1961-1965)? I.a. Why Superhero Comic Books? The winner of last year’s Astral Codex Ten book review contest was Brandon Hendrickson. Brandon wrote about Kieran Egan’s The Educated Mind. One of the foundations of Egan’s educational philosophy is that people learn through stories. He believes early education should focus on teaching lessons through myths and legends. This matches my experience. My kids’ favorite podcast is Greeking Out – a very well produced, very entertaining, National Geographic podcast about Greek Legends. Aside #1: When my oldest daughter was three years old she would ask everyone she met “Do you know any myths? Can you tell me a myth?” She especially liked asking people from different places to get myths from their local cultures. Once, she asked the question to a friend of mine who grew up in South Africa, “Can you tell me any South African myths?” He struggled for a minute and then said, “Okay! I have one! Bread never falls butter side down!”. That was not the type of myth she was looking for; nor the type of myth we will be discussing in this review. Every culture has foundational myths. These stories are entertaining and engaging, but they also teach valuable lessons about both what is important in that culture, and how people in that culture are expected to behave (or at least the Platonic Ideal of how they should behave). In the modern, Western world, we have assimilated many of these foundational stories, particularly the Greek myths. My kids definitely know the Greek myths, but they also know elements of Norse mythology, Egyptian myths, stories about Anasi from West Africa and more. More fundamentally my wife and I, while not religious ourselves, have made a point of exposing the kids to the stories from the Bible. It is not politically correct to call Biblical stories “myths”, but they serve the same purpose – shared cultural understanding of the way the world works. My wife grew up without any religion, and when she was in high school, she struggled with the metaphors and religious allegories that were omnipresent in most of the Western canon. In our culture, familiarity with the Bible is important for an educated person – whether they are religious or not – because it is the foundation of so much of the rest of our culture. I believe the other set of mythological stories that are foundational to our culture are – and by this point I am sure you see where I am going here – comic book superheroes. If true, then having more than a surface-level understanding of the most important superhero stories is important in a similar way to that knowing the Bible stories is important. “Do unto others as you would have them do unto you” is an important idea to understand. So is, “With great power comes great responsibility”. I.b. Why Marvel? While there are many independent superheroes that are not owned by major conglomerates, the superheroes who have built our modern foundational myths are currently owned by two corporations. Warner Bros. Discover owns the DC library of superheroes including Superman, Batman and Wonder Woman. In 2009 Disney purchased Marvel Comics and took ownership of their characters, including Spiderman, X-men and the Avengers. Aside #2: Marvel has sold temporary film rights to many of their characters over the years. The most relevant sales started in 1994 when Marvel sold the film rights of X-men and mutants to 20th century Fox, then in 1996, when Marvel went bankrupt, Fox picked up the rights to the Fantastic Four (and New Line picked up Blade). In 1999 Marvel sold the film rights (and live action TV, and animated TV longer than 44 minutes) of Spider-man and related characters to Columbia Pictures (part of Sony) for $7MM. Marvel actually attempted to sell ALL of their remaining Marvel IP film rights to Sony for $25MM, but the top management at Sony was not interested. Sony’s management allegedly told their chief negotiator “Nobody gives a shi*t about any of the other Marvel characters. Go back and do a deal for only Spider-Man). Disney acquired Marvel in 2009, and then Fox in 2019, bringing the two separated packages of characters all back together under one roof (Blade reverted back to Marvel in 2012). Sony still owns the rights to Spider-man but has made a deal with Disney to include some of his films within the Marvel-Disney universe. Marvel sold the film rights of The Hulk to Universal in 1990 and the current status of that agreement is complicated (the consensus is that Marvel now controls the film rights to the character, but Universal owns distribution rights to any stand-alone Hulk film, which could be why Disney let's Hulk co-star in Thor movies, but not vice versa). In the early aughts Marvel wanted to build their own film franchise, but were limited to only using their remaining “B-list” characters – Spider-man, X-men, and the Fantastic Four were all off limits. Fortunately, Kevin Feige, president of production for Marvel at the time, saw a way forward. He convinced Ike Perlmutter, Marvel CEO, to allow for the production of a series of films with the remaining characters begining with Iron Man (2008). Jon Favreau directed and cast Robert Downey Jr as Tony Stark. The film blew away expectations. Kevin’s plan of a series of movies where the characters would interconnect was suddenly feasible. Iron Man was followed by The Incredible Hulk, Thor, and Captain America: The First Avenger. None managed the box office magic of Iron Man, but all were successful enough that the plan stayed on track. In 2012 the characters were all brought together in the first Avengers film, which opened to over $200MM domestically and went on to gross more than $1.5B (which made it the 3rd highest grossing film of all time). Marvel became the first studio to take the interconnected world of their comic books and make the model work on the big screen (for a much larger audience). Once the model was proven to work, other studios tried to duplicate it. Aside #3: Warner Bros’ stumbles with the DC shared universe of Batman, Superman and the Justice League are well known, but that was actually their SECOND attempt at a shared universe. Their first attempt tried to copy the Marvel method more closely. They chose their own B-list hero and set up his first film to allow for a wider mythology. Alas Green Lantern (2011) failed at the box office and we never got stand-alone films about Sinestro (Yellow Lantern), Carol Ferris (Star Sapphire, the Violet Lantern), John Stewart (African American Green Lantern), Kyle Rayner (1990s Green Lantern), Alan Scott (original Green Lantern), or the Blue, Red, and Orange Lantern Corps. At least so far, no studio has successfully created anything with close to the traction obtained by the Marvel Cinematic Universe (MCU). Warner’s DC Extended universe (DCEU) had trifling success, but is being shelved and rebooted for a fresh attempt next year. Universal’s attempt at a “Dark Universe” kicked off with Tom Cruise in The Mummy (2017), but was dead on arrival. Paramount’s attempt to link the Transformers Universe to GI Joe at the end of Transformers: Rise of the Beasts has been appropriately mocked. Sony’s Spider-man films linked to the MCU have been very successful, but their attempt at a stand-alone non-MCU Spider-man universe using Spider-man’s villains as anti-heroes has floundered (mostly succeeding only as a source of memes). Next Mattel will be attempting to build a universe off the success of last year’s Barbie and may include Polly Pocket, American Girl, Hot Wheels, and He-Man and the Masters of the Universe (no word yet on Thomas the Tank Engine, View Master and the Magic-8 Ball, but all are apparently in development). To date, only Marvel has successfully built a “Cinematic Universe”. One potential reason for the MCU’s success is that Kevin Feige built his cinematic universe on the back of the existing interconnected universe of the comics. But those comics were not the first interconnected universe of stories. For that we would need to go back to our foundational myths. The Bible stories mostly interconnect. Adam and Eve flows into Cain and Abel. David and Goliath leads to the Wisdom of Solomon. Greek Myths DEFINITELY interconnect. Supporting characters in one Greek myth have starring roles in their own stories. The Greek pantheon of tales even have their own version of the Avengers. In the Quest for the Golden Fleece, Jason brings together the Argonauts, who included in their number Theseus (who defeated the Minotaur), Orpheus (who braved the underworld) and Hercules himself – all A-list stars in their own “franchises”. Stand alone stories that exist within an interconnected universe are rare in modern media but were common in the ancient myths that have stood the test of time. Only Marvel has successfully created a shared universe that follows the pattern of ancient myths. Only Marvel films have stand-alone stories and protagonists who exist together in an interconnected world. Something about that method of storytelling is deeply pleasing for humans across many cultures. Marvel films are the first and most successful modern version of the mythological universe, and that it is worth spending more time exploring Marvel’s underlying mythology and where it came from. I.c. Why 1961? The origins of Christianity and Judaism (and Buddhism and Hinduism) are very murky. Even Islam is far enough in the past that we only have a very rough understanding of how it came to exist. When scholars want to understand in detail how a new religion is born they are far better to look at Mormonism or, if you accept it as a religion, Dianetics. Similarly, we have versions of Greek myths that have been passed down to us, but we can never know how those myths changed from their first telling to their “final” versions. Were the stories once unrelated, and only later became crafted into a single “universe”? Or were the stories built off each other one by one (“Dad that Golden Fleece story was amazing! Do you know any other stories about the Hercules guy?”)? Or was it something in between? Perhaps the stories all existed independently, but were later crafted together (“Remember that 12-labors story I told you? Actually that was the same guy who was on the Argo!”) Unlike Greek legends, we can know the origin of the Marvel Universe. We can see how it was constructed step-by-step. The people who did it (most importantly Stan Lee, Jack Kirby, and Steve Ditko) are dead now, but they have not been dead for long. We can read the original work, see how it changed over the last 60 years, and we can ask the creators “what were you thinking at the time” (or at least read their answers from old interviews). We can’t always trust what Stan Lee says, but at least we can hear his point of view. No one has a transcript of an interview with Homer, or knows exactly what he was thinking when he called it the “wine-dark sea”. Tl;dr: Why read about Marvel Comic superheroes 1961-1965? Because interconnected mythological stories are very important to cultures, Marvel is the leading contender of the most recent modern mythology, and it originated in the first half-decade of the 1960s. II. How did Marvel Superhero Comics happen? Timely Comics published their first comic book in 1939 and called it “Marvel Comics”. Their most popular World War II comics included Captain America, the Human Torch (an android unrelated to the modern Human Torch except in powers, appearance and name), and Namor, the Submariner. In the early 1950s superheroes became less popular, so Timely changed its name to Atlas Comics and focused on humor, western, horror, war and science fiction stories. But in 1956 DC Comics began re-introducing their Golden Age superheroes and, in the second half of the 1950s, the genre took off again – particularly Superman, whose title, Action Comics, became the number one selling comic in America. Stan Lee, editor and chief at Atlas at the time, wanted to get in on the superhero action. Unfortunately in 1957 Atlas lost its distributor and the company had to rely on “Independent News” to get its comics on newsstands. The complication was that Independent News was owned by “National Periodical Publications”, who also owned DC-comics and did not want Atlas to introduce superheroes to compete with Superman, Green Lantern and the Flash. Independent News agreed to distribute Atlas comics but limited the publisher to eight titles per month, and only in non-super hero genres (like horror, romance and science fiction). Blocked from creating and launching new superhero titles, Stan Lee got creative, and in August 1961 Atlas Comics published Fantastic Four #1. Aside #4: Fantastic Four #1 was on newsstands in August 8th, 1961, but the date on the cover was November 1961. The convention at the time was that the cover date was not the “publication date” but rather the “pull date”. The pull date was the time when the retailer could send back unsold copies back to the publisher for a refund. In fact the retailer did not need to send the entire issue back, just the cover, as it was assumed that comic books could not be sold without the cover, and it saved on postage. This was only relevant because it was great for my dad who was a child at the time. My dad was friends with the kid whose father owed the local pharmacy which meant he had access to every comic book published in the late 1950s as long as he was willing to wait a few months and read it without a cover. Going forward in this essay I will always use the pull dates rather than the publication dates for individual comic book issues as they are far easier to source. If you want to convert pull dates back into publication dates you can subtract roughly two months, but it is inconsistent and sometimes longer, as was the case with Fantastic Four #1. Check out the cover of Fantastic Four #1: To the modern eye this certainly looks like a superhero comic. Four heroes with super powers fighting a giant monster. But in the eyes of publishers in 1961 this looked more like a science fiction adventure comic than something that would go head to head with Superman. Here are the covers of Action Comics (the best selling superhero comic at the time) from the three months leading up to Fantastic Four #1: Notice what they have in common? “Super Rivals”, “Super revenge”, “Super Substitutes”. And all include Superman in his blue and red tights. Fantastic Four’s cover featured super powers, but never used the word “super” and no one was wearing superhero costumes. Fantastic Four, as a superhero story, slipped under the radar because it wasn’t really a superhero story at all. It was a story about four close friends who attempted to fly into space, but then something goes wrong and they crash back to Earth. The experience changes them and they decide they now need to use their new abilities to help the rest of humanity – specifically against monsters who are invading from under the Earth. It is a fantastical science fiction story – not a superhero story. Later in his career Jack Kirby, the illustrator of the issue and co-creator of the Fantastic Four, was asked about his inspiration for the Fantastic Four heroes. He did NOT say Superman – or any superhero. He said Challengers of the Unknown. Challengers of the Unknown was an adventure story co-created by Kirby in Showcase #6 in February 1957. Here is how Wikipedia describes the Challengers origin: When acquaintances miraculously survive a plane crash unscathed, they conclude that since they are "living on borrowed time" they should band together for hazardous adventures. The four—pilot Kyle "Ace" Morgan, daredevil Matthew "Red" Ryan, strong and slow-witted Leslie "Rocky" Davis, and scientist Walter Mark "Prof" Haley—became the Challengers of the Unknown. Showcase #6, and the first appearance of the Challengers of the Unknown, by Jack Kirby Visually the Challengers and the Fantastic Four were similar. Both wore skin tight uniforms with belts and minimal decoration. The Fantastic Four’s relatively simple characterizations were practically pulled from Challengers. Reed takes on the traits of both Kyle, the leader, and Walter, the scientist. Johnny, the Human Torch is the daredevil. The Thing is “strong and slow-witted”. Sue, the only woman on the team, seems like a new addition, but is likely based on June Robbins who joined the Challengers team in Showcase #7, as an “honorary” or “girl-Challenger”. After surviving their respective “miraculous” crashes, both the Challengers and the Fantastic Four band together to help the world. They both travel through space and other dimensions, fighting mad scientists and monsters. The Fantastic Four’s early antagonists were not traditional super villains. In the first few issues they fight monsters from under the Earth (Issue #1), shape changing aliens (#2), and a charlatan who uses hypnotism to steal from his audience (#3). In issue #4 Kirby and Lee re-introduce Namor, the Submariner, one of Marvel’s top IP from the 1940s, and have him kidnap Sue. Only in Issue #5 and #6 (June and August 1962) and do we get a more standard-supervillain when Dr Doom attempts to steal the Fantastic Four headquarters and throw it into space. The next superhero Lee created was even less heroic than the Fantastic Four. In April 1962 (pull date), Marvel published The Incredible Hulk. If it was even a superhero story in disguise it was a very good disguise. The story was a scientific-filtered version of Dr Jekyl and Mr Hyde. It was a pure monster-story with nothing very super about it. Nothing on the cover suggests this has anything to do with superheroes: It is not clear if even Lee at the time thought the Hulk would be a superhero. In Fantastic Four #5 Johnny is reading a “great new comic mag” and mocks the Thing by comparing him to the Hulk. It seems pretty clear at this point that in the Fantastic Four’s world, the Hulk is just a fictional comic book, like in ours (more on that later): The other two superheroes the Marvel introduces in this period have even more subtle introductions. At the time Marvel had a number of generic-sounding titles and told science fiction and fantasy stand-alone stories: Tales to Astonish
Viibryd

Viibryd is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 31, 2021 and March 31, 2021. The archive places it in contexts such as "vilazodone ("Viibryd") seems to increase serotonin a lot more than any traditional SSRI"; ""vilazodone (\"Viibryd\") seems to increase serotonin a lot more than any traditional SSRI"". It most often appears alongside ASRI, Celexa, Cipriani.

Reference entry
Viibryd
Mention count
1
Issue count
1
First seen
March 31, 2021
Last seen
March 31, 2021
March 31, 2021 · Original source
This is pretty cool and could potentially explain why Lexapro seems to work a bit better than other antidepressants. But I don't want to fall for it too quickly. Attempts to map the exact degree of serotonin increase to antidepressant effectiveness are fraught; vilazodone ("Viibryd") seems to increase serotonin a lot more than any traditional SSRI, but doesn't work any better. It's all pretty mysterious. But maybe Viibryd increases serotonin in a mysteriously-bad way and Lexapro increases serotonin in a mysteriously-good way.
vilazodone

vilazodone is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 31, 2021 and March 31, 2021. The archive places it in contexts such as "vilazodone ("Viibryd") seems to increase serotonin a lot more than any traditional SSRI"; ""vilazodone (\"Viibryd\") seems to increase serotonin a lot more than any traditional SSRI"". It most often appears alongside ASRI, Celexa, Cipriani.

Reference entry
vilazodone
Mention count
1
Issue count
1
First seen
March 31, 2021
Last seen
March 31, 2021
March 31, 2021 · Original source
This is pretty cool and could potentially explain why Lexapro seems to work a bit better than other antidepressants. But I don't want to fall for it too quickly. Attempts to map the exact degree of serotonin increase to antidepressant effectiveness are fraught; vilazodone ("Viibryd") seems to increase serotonin a lot more than any traditional SSRI, but doesn't work any better. It's all pretty mysterious. But maybe Viibryd increases serotonin in a mysteriously-bad way and Lexapro increases serotonin in a mysteriously-good way.
ViraCoin

ViraCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 04, 2022 and May 04, 2022. The archive places it in contexts such as "You know ViraCoin? 'New crypto. You mine it by promoting about it.'". It most often appears alongside 1000, 1200, 1400.

Reference entry
ViraCoin
Mention count
1
Issue count
1
First seen
May 04, 2022
Last seen
May 04, 2022
May 04, 2022 · Original source
“You know ViraCoin?”
“New crypto. You mine it by promoting about it. Once every eight minutes, a decentralized algorithm searches for tweets containing the word ‘ViraCoin’ with a positive sentiment score, weights them by number of likes, and then picks one at random to award a ViraCoin to.”
“No, you don’t understand. This is just the first step. Once we make it super-big, we’ll introduce other things into the algorithm. Charities. Political causes. We’ll have millions of people competing to praise UNICEF in order to get that next million-dollar ViraCoin drop. If you think about it, all problems are caused by lack of awareness. We’re an at-scale solution to awareness. Solve that, and you solve poverty, inequality, racism…”
Virgin Galactic

Virgin Galactic is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2025 and October 24, 2025. The archive places it in contexts such as "The section heading would have been “Virgin Galactic”". It most often appears alongside A Ordem, Abraham Lincoln, ACX.

Reference entry
Virgin Galactic
Mention count
1
Issue count
1
First seen
October 24, 2025
Last seen
October 24, 2025
October 24, 2025 · Original source
But if He does try to trick people, He should succeed. I can’t say either of these two things with confidence. Doesn’t the Biblical God sort of try to trick Abraham into thinking he’s going to have to sacrifice his son? And what is God, anyway? Isn’t the whole world a product of God? Does the existence of mirages in the desert count as “God trying to trick people”? Does that fact that we know there are mirages imply that God failed? Still, Ethan’s take on the “sun” miracle of Fatima seems like an unusually clear-cut case of God trying to trick people and failing, and I’m uncomfortable with it. You can always add more overfitting. God’s goal was for the crowds at Fatima to be fooled, but then for Dalleur (2021) to figure it out, and so He achieved His goal perfectly. Okay. But speaking of overfitting… If I understand Ethan right, Fatima was an objective omnidirectional light show, plus a unidirectional heat ray. Ghiaie was a spotlight-shaped unidirectional lightshow. Benin City was a subjective omnidirectional light show limited to a single field, plus an objective unidirectional heat ray. God implemented all of these miracles in completely different ways. Why? Inscrutable God reasons. This isn’t a terrible answer. People often do things for reasons I can’t explain - if I could predict Trump’s behavior, my stock market returns would be much higher. And surely God, as a being with motives and knowledge far beyond my ken, should be even more incomprehensible. But there was an interesting recent Notes debate about a Bentham Bulldog’s post. BB said that atheists had many problems - how was the world created? how do you overcome skepticism? what happened at Fatima? - whereas theism only has one problem - the problem of evil. Evil is a big problem, but it’s at least nice to only have one. Some of the commenters - and I can no longer find the comment I liked anymore, but don’t take this as an original insight from me - pointed out that this is cheap. If you are an atheist, you need to answer many how questions. How did the miracle at Fatima happen? If you try to explain it with natural laws - for example, gravity - it’s fair for an interlocutor to point out that gravity can’t do that; it can only make things fall. If you’re a theist, you have a free option to convert any how question to a why question. How? Because God did it! Your interlocutor can’t object, because we know God can do anything. But in exchange, you now have a why question - why did God do that, and not something else? The sum of all why question - the fact that the real world doesn’t look like it was optimized for some specific plausible motive like goodness - is the problem of evil. Thus, it is exactly equivalent to all the inconvenient “how” questions you hoped you’d avoided. The commenter sarcastically compared this to an attempt to sweep all scientific anomalies under the rug as “the problem of uncharacteristicness”. How did Fatima happen? “Well, it must have been produced by laws of physics, so there!” But the sun spinning and dancing through the sky is hardly what you would expect from the laws of physics. “Yeah, whatever, that’s just the ‘problem of uncharacteristicness’, we’ve already priced that one in, at least we only have one problem!” This made me more attuned to questions of God’s motives. Yeah, it is kind of weird that God would create the same miracle three different ways, and we don’t know why. Yeah, it is kind of weird that God would try to trick people into thinking a non-sun-object was the sun, then let a few smart people working years later see through the deception. Are these problems of motive exactly as problematic for the theist as 70,000 people seeing the sun do impossible things is for the atheist? My gut answer is no. Should I trust my gut? Dylan: In Defense Of Evan Harkness-Murphy Evan wrote the original response to Ethan, before I got involved in the debate. I was a bit harsh on him, saying that his part about the child-seers was fine, but calling his investigation of the sun miracle superficial and unfairly dismissive. Dylan of Chaotic Neutral writes In Defense Of Evan Harkness-Murphy, and Evan additionally defends himself here. Before getting to Dylan’s post - yeah, I was unfair to Evan (partly this is because my brain has trouble remembering that Ethan Muse and Evan Murphy are two different people). In particular, I described his hypothesis on the child-seers as being that they “confabulated” their visions, a term that Evan took great pains to disclaim in his actual post. I was thinking of a broader definition of “confabulation” that includes hallucination-like phenomena - but Evan was right that if I had read his post carefully, I wouldn’t have used the specific word he said he was against. I mostly just skimmed it to see if he had a really good explanation for the sun miracle thing, then got annoyed when he didn’t. But Dylan has additional complaints. He writes: Evan DID give this miracle the attention it deserved. He spent 18 hours researching and writing his article, presenting much of the same evidence and coming to many of the same conclusions that Scott did, and he did it as an ordinary citizen with a “day job” and in a household that “does not possess a dishwashing machine.” What more could you ask of a skeptical individual!? Unlike myself and the other lazy skeptics, he actually did respect this miracle claim enough to do a proper investigation. And towards the end, yes, he decided to wrap up early […] To criticize Evan’s conduct here in this miracle debate is to set an extremely high bar that cannot possibly be met by the overwhelming majority of the skeptical community. Such exacting standards will ultimately only serve to discourage diligent skepticism like Evan’s and incentivize lazy skepticism like mine. I have two partial defenses of my own actions. First, I think the majority of those 18 hours were spent on the child-seer section, which I acknowledged was good. I didn’t care about that part. To me, the trouble of explaining how three children can say in a convincing and honest-sounding and semiconsistent way that they saw the Virgin Mary is a rounding error compared to the trouble of explaining how 70,000 people can say in a convincing and honest-sounding and semiconsistent way that they saw the sun fall from the sky. But second, I think Dylan is arguing that Evan should get an A for effort. I agree. He put in a lot of work, he adhered to good scholarly principles, and he hit all of the beats that a skeptical explanation is supposed to hit. The only thing he didn’t do, from my perspective, is defuse the fact that the Fatima miracle is extremely creepy, and I have no idea what to do with it, and I can’t fit it into my ontology. Evan’s only attempt to defuse the miracle was that it was a hallucination or illusion or something. This is a reasonable conjecture, but for me it was already priced in - as soon as you hear about a miracle, the obvious next step is “well, maybe it was a hallucination or illusion or something”. I didn’t feel like his piece added anything extra. Generously, some of his tangential points - like that Garrett and Almeida weren’t the perfect skeptics they are sometimes portrayed as - might have defused 1% of my discomfort. I think a reasonable conclusion for this would have been “I’ve rehearsed the obvious arguments for why it is possible to be skeptical of anything, I’ve found some tangential facts that maybe remove 1% of the mystery, but man, I don’t know, this really needs lots more investigation”. My research hardly provided any kind of brilliant omni-solution, but I think that learning about the Ghiaie/Benin/Lubbock/Medjugorge followup miracles and the Redditor testimonies each defused about 15% of my reluctance to accept Fatima as natural, and the fire kasina + Khomeini stuff defused another 10%, to the point where I’m only about 60% as confused and unhappy as when I started. I hope I correctly signposted this level of success/failure to the reader. On Miracles Other responses tried to assert a general point that we should always disbelieve miracles. I. Eugene Earnshaw writes that We Do Not Need To Care About Miracles. If I understand his argument right: there are many examples of anomalous phenomena (eg crop circles) and stage magic (eg sawing a woman in half). When we don’t know how these are done, they seem impossible, and (almost) no amount of armchair reasoning can produce a plausible explanation. But in many cases, we have eventually figured them out - some “white hat” crop circlers explain how they make their seemingly-impossible patterns, and some magicians publish explanations of their tricks. After the fact, we can see how these seemingly-impossible things followed natural law after all. So we shouldn’t worry too much each time we encounter a new miracle that hasn’t yet been explained. Okay, but - suppose that the Pope said “I’m tired of convincing you people the normal ways, I’m going to start blowing up mountains”, and pointed his papal staff at Mt. Everest, and it exploded. And then we asked him to repeat the performance, and he did so as many times as we asked him, again and again. Would we shrug and say “Nothing to see here, I’m sure there’s some reasonable explanation”? If the miracle were sufficiently convincing, we would either believe it, or at least think it pointed at something interesting (maybe the Vatican obtained super-nukes and is hiding them under mountains and choreographing their detonations - but this would be pretty important and very different from “nothing to see here”). Ben Landau-Taylor gives a related answer, reminding us that meteorites used to be dismissed on exactly these grounds. The science of the day didn’t allow for non-planet objects to be in space, so rocks falling from the sky was every bit as weird as the sun dancing and changing colors. “When President Jefferson was told that Professors Silliman and Kingsley had described a fall of stones from the sky at Weston, in Connecticut, he remarked: ‘It is easier to believe that two Yankee professors will lie than to believe that stones will fall from heaven.’” In the end, I think we just get back to regular Bayesianism. We have two hypotheses: First, that the world acts entirely according to natural law. Second, that sometimes it includes divine intervention (or very surprising natural laws that we wouldn’t have predicted beforehand). We start with a high prior on the first hypothesis based on our long history of seeing only natural events. When we see evidence that is more likely on the second hypothesis than the first, we update in favor of it. We should remember that “more likely on the second hypothesis than the first” is full of pitfalls - on the first hypothesis, it’s likely that there will be many skilled fraudsters and stage magicians, so even very strange-seeming anomalies might not be very unlikely under it. Still, at the point where the Pope starts blowing up mountains, maybe you think it’s pretty unlikely that stage magic could accomplish this, and you update a little. II. Omne Bonum makes a different point: there are many possible miracles. Most do not occur. Yes, a few of them do. But can we be sure it’s above the background rate? Even if there are no true miracles, you’ll get one-in-a-million coincidences one-millionth of the time. If you’re not good at accounting for the 999,999 failures - and people aren’t - this will look impressive. Against this, what is the base rate for the sun changing color and dropping out of the sky, at the precise time that child-seers prophecied a miracle would occur? Seems lower than one in a million. Impossible things should never happen. Something as simple as my pen vanishing from my desk, in plain sight, while I am looking straight at it, should completely demolish all of my priors against miracles and make me near-certain that something beyond normal physical law is going on - or that I’m crazy, or dreaming, or something other than just “well it was a coincidence”. III. FLWAB takes on Hume’s argument against miracles (see also Kenny Easwaran here), which - sorry, I realize it’s suspicious to say this about a famous philosopher - is extremely bad. Hume argues that a miracle is a violation of natural law. And a natural law is something that is always true. But since it’s always true, it can’t be violated. And if we eventually confirmed that it was violated, then we were wrong about it being a natural law. Which means its violation wasn’t even a real miracle anyway. This seems to be a purely semantic argument. We know that the Red Sea usually stays in one place. But suppose Moses lifts his staff and parts the Red Sea, and that all of this is very convincing (we witness it personally, we measure the sea with various instruments, etc). I think Hume would have to say that we have disproven the natural law “the Red Sea usually stays in one place” - but only in favor of a new natural law “the Red Sea stays in one place except when Moses raises his staff”. And since we have never observed a violation of this new natural law, no miracle has occurred! Against this, we can call the way things work 99.999% of the time, when God isn’t acting directly, and when everything is proceeding via predictable material patterns “natural law”, and the very rare deviations that only occur in the presence of God or other extremely holy figures “miracles”. If for some reason you hate that terminology, come up with a new word, “shmiracle”, for the abnormal phenomena that only occur secondary to God’s direct intervention, and then we can argue whether shmiracles exist. IV. Why am I insisting on this so hard? This question of miracles is no different from every other question, where confirmation bias is a part of normal Bayesian reasoning. If you believe that vaccines don’t cause autism, then any given study showing that they do is likely to be a fraud or a mistake - especially given the history of such frauds, and the political pressures for producing them. But you gained your belief that vaccines don’t cause autism through some normal amount of evidence, and if the evidence that they did cause it ever become truly overwhelming, you would switch sides. The key skill of rationality is to know when to update your beliefs how much. These arguments feel like sleights-of-hand arguing that you can avoid ever updating on this question. I don’t think Bayesian reasoning provides an excuse for this. I think some of these arguments attempt to make an objection that the prior probability of miracles is zero, and so no matter how much evidence you get, you can never update towards them. But the prior probability of miracles isn’t zero unless either the prior probability of God’s existence is zero, or the probability that God intervenes in the universe is zero. I don’t know any infinitely-convincing argument for either of these points, so I think miracles have a prior probability above zero, which means we have to treat them the same as any other hypothesis. Yes, we will need many extra guardrails and cautions and good heuristics to prevent ourselves from getting bamboozled by the pitfalls that lurk in this area in particular. But that’s true of everything! You also need extra guardrails and cautions and heuristics to prevent yourself from getting bamboozled by scientific studies! There’s no substitute for doing the work. Actual Highlights From The Actual Comments Josh (blog) writes: I’d add that we have at least one verified case where a sun miracle was occuring, and an actual group of fedora wearing atheists were present with a modified telescope, and did not see anything interesting. >> “At the Conyers site, the Georgia Skeptics group set up a telescope outfitted with a vision-protecting Mylar solar filter, and on one occasion I participated in the experiment. Becky Long, president of the organization, stated that more than two hundred people had viewed the sun through one of the solar filters and not a single person saw anything unusual (Long 1992, 3; see figure 1).” https://centerforinquiry.s3.amazonaws.com/wp-content/uploads/sites/29/2009/11/22164423/p14.pdf Funny, but they don’t provide information like whether people were seeing sun miracles at the exact moment the telescope was being used, or whether anyone who could see a sun miracle without the telescope switched to using the telescope and then it stopped. They just say they brought a telescope to a Marian site where some people had seen sun miracles at some point. Even if they clarified that some people had used the telescope while seeing a sun miracle and had it immediately stop miracle-ing, I don’t think this would update me very much. We know it’s not the real sun (Ethan says fake sun, I say subjective phenomenon), and we know the non-Fatima miracles aren’t objective (Ethan says only Fatima was objective, I say none of them were objective). John Schilling writes: Twenty-nine *thousand* words on this subject, and none of them are “unidentified”, “flying”, or “object”. Well, OK, there are a few uses of that last, but in the strained phrasing of “UFO-like object”, as if we are preemptively discounting the possibility that sun miracles are actually UFOs. Sun miracles are actually UFOs, full stop. Not “flying saucers”, not “alien spaceships”, maybe “divine miracles”, but definitely “unidentified flying objects”. We invented that last phrase for a reason, and this is exactly that reason. Which means, the thing I learned from this is that the younglings have completely forgotten all that was learned in the Before Times about UFOs. And that, in this context, Scott is a youngling - UFOs seem to have faded from pop culture in the 1990s. Thanks for making me feel old, Scott :-) With the benefit of age and experience, I read the first few paragraphs, made the tentative conclusion that this was almost certainly [see section 6], but figured Scott wouldn’t be doing this deep a dive if it was that simple. And here we are. It probably is just that simple, and now we can back that up with a fairly exhaustive look at the alternatives. For which, unironically, thank you Scott. It’s good to sometimes double-, triple-, and quadruple-check the obvious conclusion. But for those of us who grew up in the 1980s, who were “rationalists” when rationalism hadn’t been invented and we had to call ourselves “skeptics”, UFOs were as important a subject of rationalist/skeptical inquiry as is AI risk today (and for about the same reason). People learned an awful lot in those days. One of those things is that most people don’t spend much time really looking at the sky and will consistently fail to recognize even slightly-unusual phenomena, like the sun partially veiled by clouds. And the other, more important thing is that when presented with an image they don’t recognize, people will very predictably see what their culture has taught them to expect to see. In 1880s-1890s America, any weird thing in the sky was clearly a fantastic airship, built by some mad scientist out of a Jules Verne novel, and was perceived with a wealth of surrounding detail all aligned with that model. 1950s-1980s America, the same things were clearly “flying saucers”, fantastic alien spaceships piloted by little green or grey men, with the same level of impossible detail. And anywhere you’ve got ten thousand devout Catholics fervently hoping to see a Miracle involving the Sun, and the weather makes the sun look a bit wonky... For an old-school skeptical experiment at understanding this effect, https://centerforinquiry.s3.amazonaws.com/wp-content/uploads/sites/29/1980/04/22165441/p34.pdf TL, DR, a gathering of UFO enthusiasts expecting to see a flying saucer in the night sky, are presented with thirty seconds of a monochromatic point source of light at ground level, stationary and unchanging except for one brief interruption. What is perceived, is an object high in the sky with finite angular size and geometric shape, of multiple colors, and conspicuously moving, all consistent with the pop-culture concept of a flying saucer and not some prankster with a spotlight. I considered discussing the UFO angle (the section heading would have been “Virgin Galactic”), but in the end I couldn’t justify it. Yes, the phenomenon is trivially a UFO (in the sense of a thing in the sky we don’t understand). But does this help us? When I think of UFOs, I think of people arguing about whether something was the planet Venus, or a weather balloon, or aliens. But Fatima obviously wasn’t Venus or a balloon (though, uh, see here for a dissenting take). And if it was aliens, you’d have to explain why they pretended to be the Virgin Mary and discussed a bunch of Catholic inside-baseball with a trio of child-seers for several months. So what’s left? When I asked John, he answered: UFOs, are just people seeing something they don’t understand and trying to interpret it by an overweighted, culturally-transmitted prior. Which differs from culture to culture. And that’s something we know a lot about. Which you seem to have independently rediscovered, but I can’t help thinking you’d have got there a lot faster if you’d had a proper map of the territory. A map which includes no aliens outside of the imaginary sort. Maybe one way to rescue the UFO connection is to say that there’s so much weirdness that we should be less willing to take any given example of weirdness on its own terms. I asked in the comments for other examples of miracles as compelling as Fatima. People suggested some of the better-verified reincarnation accounts, some of the better-verified UFO sightings, and some of the more spectacular psi phenomena. I don’t know if these are all exactly as strong as Fatima, but I think many of them are closer to Fatima than to the traditional skeptical conception of an alcoholic liar asserting with zero evidence that he dun saw dem aliens one night. When viewing all of these anomalies as a gestalt, we can go four different directions: Individualized natural explanations. The UFOs were swamp gas and weather balloons. The reincarnation stories are toddlers who are naturally gifted at cold reading. Fatima was entoptic phenomena. Sea serpents are really big oarfish.
Virgin Records

Virgin Records is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 01, 2025 and October 01, 2025. The archive places it in contexts such as "Bibliography: Virgin Records". It most often appears alongside 1910s Portugal, 1999 British eclipse, 2017 US eclipse.

Reference entry
Virgin Records
Mention count
1
Issue count
1
First seen
October 01, 2025
Last seen
October 01, 2025
October 01, 2025 · Original source
I know that everyone who sees hallucinations says they look completely real, and if someone says the sun miracle looks completely real with 0% chance it’s just an optical illusion I probably won’t update at all - but I still have a perverse urge to interview someone who saw the miracle and ask them “so, did it really look completely real?” in a hundred different phrasings, and see if that helps in some way. Again, please don’t research this by staring at the sun. Bibliography: Virgin Records In the process of writing this post, I collected a trove of Fatima data. Some of it came from long Googling or GPT queries; others from setting up a pipeline of PDF splitters, OCR software, and machine translation. In case it helps future researchers, I’m including the some of the most precious and hardest-to-find resources below. My spreadsheet of ~60 eyewitness accounts with chain-of-transmission.
VPN

VPN is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 07, 2024 and November 07, 2024. The archive places it in contexts such as "you have to get a VPN". It most often appears alongside 538, Bayes’ Theorem, Betfair.

Reference entry
VPN
Mention count
1
Issue count
1
First seen
November 07, 2024
Last seen
November 07, 2024
November 07, 2024 · Original source
Why not? In order for an American to use Polymarket, you have to get a VPN, a Coinbase account, and a Metamask wallet, use the VPN, get crypto on the Coinbase account, transfer it to the Metamask wallet, connect the Metamask wallet to Polymarket, and buy the shares you want. Ability to do this rules out 99% of the US population.
VR headset

VR headset is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 07, 2023 and November 07, 2023. The archive places it in contexts such as "maybe if I didn’t donate, I would buy the new VR headset that just came out". It most often appears alongside Aceso Under Glass, ACX Grant, America.

Reference entry
VR headset
Mention count
1
Issue count
1
First seen
November 07, 2023
Last seen
November 07, 2023
November 07, 2023 · Original source
That’s probably a bit counter intuitive - what could be most costly than my literal time and resources? That’s all I have! Here’s my thinking: after donations, I still live a life of extreme wealth and comfort compared to the average human, so the opportunity costs of donation are kinda trivial (like, maybe if I didn’t donate, I would buy the new VR headset that just came out, but I don’t suffer greatly because I haven’t done so). As for my job choices, these have coincidentally (suspiciously I might add, in my moments of doubt) been things I find challenging and interesting and rewarding in and of themselves. On top of that, there’s the point you mention that lots of my preferred ways to do good aren’t actually seen as good at all by plenty of critics (and, like, many everyday people too). I’m somewhat prone to imposter syndrome, and it’s easy for me to doubt my own motivations and impact on the world.
VSCode

VSCode is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 10, 2022 and February 10, 2022. The archive places it in contexts such as "Cursorless, the state-of-the-art open-source voice editing framework for VSCode". It most often appears alongside 2018, @BendiniUK, @benyeohben.

Reference entry
VSCode
Mention count
1
Issue count
1
First seen
February 10, 2022
Last seen
February 10, 2022
February 10, 2022 · Original source
#95: Make Programming By Voice More Practical I'm Michael Arntzenius (rntz.net) and I'd like $5-40K to work on making programming by voice more practical. Many programmers at some point suffer from repetitive strain injuries (RSI) that make typing difficult; I'm one. To mitigate this I use a tool called Talon that lets me control my computer by voice. Thanks to recent advances, voice control is increasingly practical, and voice programmers form a small but rapidly growing community. However, idioms and tools for coding by voice are in their infancy. I believe now is the right time to push hard on voice-oriented editing: the underlying voice recognition tech is ready, we have a creative, dedicated community willing to experiment with new approaches, and mature editor technology like language servers and online error-robust parsing (eg. tree-sitter) supports editing commands at a higher level than character-by-character. Specifically, this money could support me working part-time for 6 months ($5k) up to full time for 2 years ($40K). I could work on: contributing to Cursorless, the state-of-the-art open-source voice editing framework for VSCode; porting cursorless to other editors to increase its reach; incorporating ideas from recent research on structural editing and typed holes; and on my duties as co-maintainer of the de-facto default Talon script-set. If you're interested, contact me at daekharel@gmail.com.
W88

W88 is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between January 07, 2022 and January 07, 2022. The archive places it in contexts such as "we can throw in enough 475 kT W88 warheads". It most often appears alongside ACX Discord, Aerojet XLR-132, Aimable.

Reference entry
W88
Mention count
1
Issue count
1
First seen
January 07, 2022
Last seen
January 07, 2022
January 07, 2022 · Original source
Except, this assumes we can Thanos-fingersnap the warheads into existence right next to the comet as soon as Plucky Male Astronomer and Plucky Female Astronomer discover it. More realistically, assume we spend three months building the hardware(*), and two months flying it out to meet the comet with our clumsy slow rockets, conducting the diversion effort only one month before impact. Now we need 1100 warheads minimum. I don't think we've actually got 1100 B83's, but we can throw in enough 475 kT W88 warheads to make up the difference. We're not spacing these out by hours each, obviously, so cross your fingers and hope your models were right.
Warhammer

Warhammer is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 03, 2023 and June 03, 2023. The archive places it in contexts such as "the price of a Warhammer starter set". It most often appears alongside 2023 book review contest, AGI, Alan Turing.

Reference entry
Warhammer
Mention count
1
Issue count
1
First seen
June 03, 2023
Last seen
June 03, 2023
June 03, 2023 · Original source
Why Machines Will Never Rule the World is 301 pages before you hit the appendices. You can buy the paperback from the publisher or on Amazon for $48.95, almost exactly the price of a Warhammer starter set or 800 grams of Dutch baby formula.
Waymo

Waymo is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2024 and October 24, 2024. The archive places it in contexts such as "companies like Waymo and [I can’t remember which other ones he named]". It most often appears alongside 1960: The Year The Singularity Was Cancelled, 1960s, 1973.

Reference entry
Waymo
Mention count
1
Issue count
1
First seen
October 24, 2024
Last seen
October 24, 2024
October 24, 2024 · Original source
After a few disappointing years, these are finally coming into their own. The expert I talked (EDIT: I try to mostly preserve anonymity in this post, but this person has kindly allowed me to identify him as Andrew Miller of Changing Lanes) to said Tesla had made some bad decisions and was no longer in the top tier, but that companies like Waymo and [I can’t remember which other ones he named] were near the finish line. They’re already safer than humans in most situations and operating successfully in several cities. The remaining challenges to scaling up are mostly regulatory, not technical. Here the regulatory challenges are less about specific laws than general nervousness on the corporations’ part to be seen expanding too quickly. They want to build a strong record in friendly cities before venturing further.
Weeve

Weeve is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 10, 2023 and November 10, 2023. The archive places it in contexts such as "an Irish company called Weeve does this (almost) exactly as described". It most often appears alongside #EEGManyLabs, 23andme, @freeshreeda.

Reference entry
Weeve
Mention count
1
Issue count
1
First seen
November 10, 2023
Last seen
November 10, 2023
November 10, 2023 · Original source
4 (Language learning technique): Several people linked to groups that are already trying this. I was most excited by Weeve, but there’s also Prismatext, The Adventures Di Pinocchio, and DonQuixote.fun. If any of you try any of those, let me know how it goes.
Re: language learning, an Irish company called Weeve does this (almost) exactly as described.
https://shop.weeve.ie/pages/shop
Wellbutrin

Wellbutrin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between April 14, 2021 and April 14, 2021. The archive places it in contexts such as "bupropion (“Wellbutrin”), the fourth-most prescribed antidepressant in the US". It most often appears alongside Alaska, America, Amisulpride.

Reference entry
Wellbutrin
Mention count
1
Issue count
1
First seen
April 14, 2021
Last seen
April 14, 2021
April 14, 2021 · Original source
Likewise, Próspera has 100% drug approval reciprocity. If a drug has been approved in an OECD country (eg by the FDA), it’s approved in Próspera. Again, close to my heart. Amisulpride is a great antipsychotic, probably better then most of the ones we use here. It’s approved in Europe, the UK, Australia, Israel, etc, where many studies have shown it’s safe and effective. Because none of those studies were done in the US, the FDA refuses to approve it here, and has demanded several hundred million dollars worth of more studies, which the company involved has chosen not to do (an injectable version was recently approved for nausea, but can’t be easily used for psychosis). Meanwhile, bupropion (“Wellbutrin”), the fourth-most prescribed antidepressant in the US, isn’t approved for depression in Britain; the subset of patients who respond to this medication and nothing else are out of luck. Próspera will be one of the only places in the world where patients will have access to amisulpride, bupropion, and all the other medications that one country or another is restricting because “it wasn’t invented here”.
WhatsApp

WhatsApp is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between November 08, 2021 and November 08, 2021. The archive places it in contexts such as "villagers an almost hour-long voice message over WhatsApp"; "voice message over WhatsApp". It most often appears alongside America, Apolo Group, Ashkenazi.

Reference entry
WhatsApp
Mention count
1
Issue count
1
First seen
November 08, 2021
Last seen
November 08, 2021
  • 21 November 08, 2021
November 08, 2021 · Original source
In June 2020, Brimen, who was stuck in the U.S. due to Covid travel restrictions, sent villagers an almost hour-long voice message over WhatsApp. Próspera would never seek or accept expropriated land, he said. Brimen cataloged all that Próspera’s foundation had done for Crawfish Rock, finally turning to the water supply, for which Próspera had agreed to stop billing during the pandemic. His tone veered from disappointment to veiled threats. “Wow,” he said, in a breathy whisper of faux-astonishment, “how terrible, eh? To live in this modern age and lack running water.” He went on: “Running water to your home, such a basic yet transformative and essential service.” A pause for effect. “Who did that?”
Windows

Windows is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 18, 2023 and September 18, 2023. The archive places it in contexts such as "Musk's expertise was with Windows and not Oracle". It most often appears alongside 787, adderallposting, ADL.

Reference entry
Windows
Mention count
1
Issue count
1
First seen
September 18, 2023
Last seen
September 18, 2023
September 18, 2023 · Original source
And yet, Levchin began to marvel at the counterexamples [to his generally low opinion of Musk], such as when Musk astounded him by knowing things. At one point, Levchin and his engineers were wrestling with a difficult problem involving the Oracle database they were using. Musk poked his head in the room, and even though his expertise was with Windows and not Oracle, immediately figured out the context of the conversation, gave a precise and technical answer, and walked out without waiting for confirmation. Levchin and his team went back to their Oracle manuals and looked up what Musk had described. "One by one, we all said, 'S**t, he's right," Levchin recalled. "Elon will say crazy stuff, but every once in a while he'll surprise you by knowing way more than you do about your own specialty. I think a huge part of the way he motivates people are these displays of sharpness, which people just don't expect from him, because they mistake him for a bullsh***er or goofball."
WordTwist

WordTwist is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between August 09, 2021 and August 09, 2021. The archive places it in contexts such as "The game was WordTwist, which you can find here (warning: potentially addictive)". It most often appears alongside Amazon, Berkeley, KPier.

Reference entry
WordTwist
Mention count
1
Issue count
1
First seen
August 09, 2021
Last seen
August 09, 2021
August 09, 2021 · Original source
The game was WordTwist, which you can find here (warning: potentially addictive). You get a 5x5 square of letters and you have to find as many words as possible (of four letters or more) within three minutes. You can move up, down, right, left, or diagonal, and get more points for harder words. A typical board looks like this:
WorldCoin

WorldCoin is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2024 and March 12, 2024. The archive places it in contexts such as "Sam Altman’s WorldCoin has quadrupled in value this month". It most often appears alongside Asterisk, Bard, Berkeley.

Reference entry
WorldCoin
Mention count
1
Issue count
1
First seen
March 12, 2024
Last seen
March 12, 2024
  • 24 March 12, 2024
March 12, 2024 · Original source
4: Also in crypto: Sam Altman’s WorldCoin has quadrupled in value this month. Some of this is the general crypto rally, but it also seems to go up whenever OpenAI does something cool, suggesting it’s more of a “how popular is Sam Altman and his company right now” memecoin than anything else. This ties back to some of our old discussion on using memecoins to track people and companies that can’t or won’t sell you real stocks. This isn’t investment advice, but WorldCoin might be in some sense a shadow OpenAI stock right now.
Xanadu

Xanadu is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2025 and September 19, 2025. The archive places it in contexts such as "In 2014, a primitive Xanadu demo was released on the Web". It most often appears alongside 1987, 1988, Adleman.

Reference entry
Xanadu
Mention count
1
Issue count
1
First seen
September 19, 2025
Last seen
September 19, 2025
September 19, 2025 · Original source
compilable "Command Meta Language" Live on stage, in the year 1968, Engelbart started up the NLS, opened a document, and typed some words into it. The words, he said, constituted a statement. And statements made up a file. Engelbart copied, manipulated, saved, and loaded his words and statements and files, zipping around with his newly-invented mouse. He demonstrated his ability to embed documents in one another—images with links to statements, words nested and categorized by one another, files filled with metadata. And then he paused, and the screen went blank. He explained that he and his colleagues at the ARC had been using this system to do their daily work for the last six months. He mentioned that they had, now, six consoles up and running. He showed the crowd a real document, then navigated to a statement within it. “This presentation is devoted to the AHIRC.” “What is the AHIRC?” he asked. Engelbart “froze” the initial statement, clicked on the acronym, and below the words “Augmented-Human-Intellect Research Center” appeared. He kept clicking and freezing, and a trail of nested and related information appeared—a list of funders, a graph of staffing over time, a mission statement. This was hypermedia. These were hyperlinks, he explained. NLS was a hypertext system. The presentation went on for 90 minutes longer, and became known as The Mother of All Demos.2 At around the 75-minute mark, Engelbart shows that two different NLS users could edit a single document simultaneously. While this was extremely impressive functionality, it was achieved with time-sharing—computation was done on a single machine, switching rapidly between tasks—and became infeasible the very next year, when ARPANET was released and the number of machines you could connect to one system grew rapidly. Engelbart’s hypertext system was impressive in its own right, even without collaborativity. And still, little came of it—Andy van Dam, an attendee and revolutionary computer scientist himself, would reflect decades later: “Everybody was blown away … and nothing else happened. There was almost no further impact.” Engelbart’s ideas were just a little too out there. ARC quickly faded into obscurity. In 1972, Engelbart joined an organization called Erhard Seminars Training. EST, or “est” as it was marketed, offered a 60-hour self-improvement course for tech entrepreneurs modeled loosely on Zen Buddhism. Critics suggested that the est course was a mind-control method aimed at raising an authoritarian army. It was quite credibly branded a cult. The founder of est, Werner Erhard, was accused of tax fraud (he fought the claims and won $200,000 from the IRS) and incest (by his daughter, who later recanted). Engelbart served, for many years, on est’s board of directors. His researchers all left for greener, less cult-y pastures, and ARC died with hardly a whimper. No one really wanted to associate with Engelbart. His crackpot theories about an internet modeled after the memex fell into disrepute, and, if he was remembered at all, it was for the invention of the mouse. No one cared anymore about the memex, or hypertext. 3. Hyper-dreams of Hyper-everything Well, one man cared. Ted Nelson was born in 1937 to two twenty-year-olds, Ralph Nelson and Celeste Holm. His parents divorced in 1939, leaving him to be raised by his grandparents. Both Nelson (the elder) and Holm would go on to extremely-successful film careers: the former became an Emmy-winning director; the latter an Oscar-winning actress. And, at first, Ted seemed to be following in their footsteps. As a philosophy major at Swarthmore College, he produced a film called The Epiphany of Slocum Furlow, which he described as “a short comedy about loneliness at college and the meaning of life.”3 Nelson also claims to have “[d]irected [and written] book and lyrics for what was apparently the first rock musical” in his junior year at Swarthmore. Thankfully, his interest in a career as an entertainer soon waned, and Nelson went off to study sociology in grad school—first at the University of Chicago, then at Harvard. Nelson took a computer class at Harvard, in 1960, and “[his] world exploded.”4 He realized the incredible power of computing, quickly intuited that these new machines could be generally applied to everything, and founded Project Xanadu.5 Initially, Xanadu’s scope was pretty limited. Word processors weren’t around yet, but Nelson wanted to build something strikingly similar: he wanted to write a program that could store and display documents, with version histories and edits all stored and displayed at the same time too. Later, Nelson would call this version-history feature “intercomparison.” (Strange coinages will be a… theme; I’m just trying to get you ready.) Nelson began working on an implementation, but his feature wishlist grew quickly, and he didn’t really know what he was doing, so in 1965, he sought help. He prepared a talk for the Association for Computing Machinery, and dropped, quite frankly, a bomb on the audience: The kinds of file structures required if we are to use the computer for personal files and as an adjunct to creativity are wholly different in character from those customary in business and scientific data processing. They need to provide the capacity for intricate and idiosyncratic arrangements, total modifiability, undecided alternatives, and thorough internal documentation. The original idea was to make a file for writers and scientists, much like the personal side of Bush's Memex, that would do the things such people need with the richness they would want. But there are so many possible specific functions that the mind reels. These uses and considerations become so complex that the only answer is a simple and generalized building-block structure, user-oriented and wholly general-purpose. The resulting file structure is explained and examples of its use are given. Ted Nelson was building the memex. Of course, he wasn’t a very technical guy, and so his talk mostly focused on the philosophy of Xanadu, not its implementation. He commented (emphasis mine): There are three false or inadequate theories of how writing is properly done. The first is that writing is a matter of inspiration. While inspiration is useful, it is rarely enough in itself. “Writing is 10% inspiration, 90% perspiration,” is a common saying. But this leads us to the second false theory, that “writing consists of applying the seat of the pants to the seat of the chair.” Insofar as sitting facilitates work, this view seems reasonable, but it also suggests that what is done while sitting is a matter of comparative indifference; probably not. The third false theory is that all you really need is a good outline, created on prior consideration, and that if the outline is correctly followed the required text will be produced. For most good writers this theory is quite wrong. Rarely does the original outline predict well what headings and sequence will create the effects desired: the balance of emphasis, sequence of interrelating points, texture of insight, rhythm, etc. We may better call the outlining process inductive: certain interrelations appear to the author in the material itself, some at the outset and some as he works. He can only decide which to emphasize, which to use as unifying ideas and principles, and which to slight or delete, by trying. Outlines in general are spurious, made up after the fact by examining the segmentation of a finished work. If a finished work clearly follows an outline, that outline probably has been hammered out of many inspirations, comparisons and tests. Between the inspirations, then, and during the sitting, the task of writing is one of rearrangement and reprocessing, and the real outline develops slowly. The original crude or fragmentary texts created at the outset generally undergo many revision processes before they are finished. Intellectually they are pondered, juxtaposed, compared, adapted, transposed, and judged; mechanically they are copied, overwritten with revision markings, rearranged and copied again. This cycle may be repeated many times. The whole grows by trial and error in the processes of arrangement, comparison and retrenchment. Nelson recognized that the creation of knowledge is cyclical, recursive, self-referential. And he figured that our computer systems should accept and reflect that process: If a writer is really to be helped by an automated system, it ought to do more than retype and transpose: it should stand by him during the early periods of muddled confusion, when his ideas are scraps, fragments, phrases, and contradictory overall designs. And it must help him through to the final draft with every feasible mechanical aid—making the fragments easy to find, and making easier the tentative sequencing and juxtaposing and comparing. How do you design such a system? To navigate intuitively within complex file systems, between document versions, and across source materials—to access all the scraps and fragments writers need to write—you would need to establish what Vannevar Bush called “tracks.” You would need to connect and save different ideas, linking them together. That was it—you needed links. Nelson went further, though—it wouldn’t do to simply have links to all the other files, a writer needed to see the other files before him, needed them to be brought up and displayed alongside his current work on demand. The links needed to contain their targets within themselves—so Nelson called them hyperlinks. And he called text embedded with hyperlinks hypertext, and movies embedded in his structure became hyperfilms, and so on. Nelson wanted us using computers to write and create self-referential, intricately-interconnected (“intertwingled,” as he’d later put it), eminently-accessible hypermedia. And recall, in 1965, state-of-the-art computing looked like this. Ted Nelson was thinking far, far ahead. Maybe too far ahead. Conference attendees were initially excited about his idea, but when he revealed himself to know very little about the technical task of building Xanadu—or even whether it was possible at all—interest evaporated. 4. Failing to Develop Xanadu But Nelson was all in. He would later write, “This is not a technical issue, but rather moral, aesthetic and conceptual.” Nelson loved knowledge and connection and abstraction—mere technical details wouldn’t stop him from building the best possible computer system for producing and consuming information. He met Doug Engelbart in the mid 60s, forming a friendship with the only other man taking hypertext seriously at the time, and hopped around unhappily between various academic and scientific appointments. At one point, he and Andy van Dam worked together and produced the Hypertext Editing System—released in 1967, just before Engelbart’s NLS. It was the first computer application to ever have an “undo” button—Nelson claims to this day that he invented it (and the “back” button). Shortly thereafter, Nelson’s wife left him. In his 2010 autobiography, he writes, “She, reasonably, wanted a Nice Life; women want that sort of thing.” They had a son, whom Nelson continued to visit regularly. “Debbie has been a friend and great support all these years,” Nelson adds. “[S]he believed in me.” Nelson gave a talk at Union Theological Seminary in 1968 that included this slide, which Nelson considers “the first depiction of what the personal computer turned out to be.” “About six years later they started building computers like this at Xerox PARC.” Around the same time, Nelson claims to have called Vannevar Bush and told him about Project Xanadu. Bush “wanted very much to discuss it with” Nelson, but Nelson “hated him instantly [because] he sounded like a sports coach” and never contacted him again. This, of course, proved to be extremely self-destructive (though I can’t honestly say I would’ve done otherwise). Because Xanadu was as good as dead. No one would give him the money he needed to work on it, especially not after Doug Engelbart poisoned the idea of hypertext. Nelson went where there was funding, working briefly on an early word processor called Juggler of Text (JOT). …And then he lost investment, stopped working on the project, and moved to Chicago, where he’d been offered a job teaching at the University of Illinois, to start work on a book. He would call it Computer Lib. In fact, he started work on another book at the same time, called Dream Machines. By the time he completed each of them, in 1974, ARPANET had been released, and his vision for Project Xanadu had evolved. He published the two works together—Computer Lib was his lamentation over the industry’s disdain for hypertext, and Dream Machines was Xanadu’s manifesto. Nelson designed and printed the book himself. Its pages mostly look like this: Self-referential, multimedia, creative, and fun—they were a blueprint for the internet he was building. In the Dream Machines half, Nelson writes, “The real dream is for ‘everything’ to be in the hypertext. Everything you read, you read from the screen (and can always get back to right away; everything you write, you write at the screen (and can cross-link to whatever you read).” In one section Nelson asks himself, “Can It Be Done?” His answer: “I dunno.” Remember, Xanadu wouldn’t only involve links between works—it required hyperlinks, which as Nelson understood them, would need to contain the targets in themselves. (Eventually, Nelson would give these embeddings a new name—“transclusions”—and hyperlink came to simply mean “link between hypertext files.”) Every link would run both ways, each hypertext file would know exactly which other files were linked to it and how. This introduced a few problems, in the new interconnected ARPANET age: How do you keep track? Where’s the metadata stored? Can you afford enough space for it all?
Ted Nelson was thinking far, far ahead. Maybe too far ahead. Conference attendees were initially excited about his idea, but when he revealed himself to know very little about the technical task of building Xanadu—or even whether it was possible at all—interest evaporated. 4. Failing to Develop Xanadu But Nelson was all in. He would later write, “This is not a technical issue, but rather moral, aesthetic and conceptual.” Nelson loved knowledge and connection and abstraction—mere technical details wouldn’t stop him from building the best possible computer system for producing and consuming information. He met Doug Engelbart in the mid 60s, forming a friendship with the only other man taking hypertext seriously at the time, and hopped around unhappily between various academic and scientific appointments. At one point, he and Andy van Dam worked together and produced the Hypertext Editing System—released in 1967, just before Engelbart’s NLS. It was the first computer application to ever have an “undo” button—Nelson claims to this day that he invented it (and the “back” button). Shortly thereafter, Nelson’s wife left him. In his 2010 autobiography, he writes, “She, reasonably, wanted a Nice Life; women want that sort of thing.” They had a son, whom Nelson continued to visit regularly. “Debbie has been a friend and great support all these years,” Nelson adds. “[S]he believed in me.” Nelson gave a talk at Union Theological Seminary in 1968 that included this slide, which Nelson considers “the first depiction of what the personal computer turned out to be.” “About six years later they started building computers like this at Xerox PARC.” Around the same time, Nelson claims to have called Vannevar Bush and told him about Project Xanadu. Bush “wanted very much to discuss it with” Nelson, but Nelson “hated him instantly [because] he sounded like a sports coach” and never contacted him again. This, of course, proved to be extremely self-destructive (though I can’t honestly say I would’ve done otherwise). Because Xanadu was as good as dead. No one would give him the money he needed to work on it, especially not after Doug Engelbart poisoned the idea of hypertext. Nelson went where there was funding, working briefly on an early word processor called Juggler of Text (JOT). …And then he lost investment, stopped working on the project, and moved to Chicago, where he’d been offered a job teaching at the University of Illinois, to start work on a book. He would call it Computer Lib. In fact, he started work on another book at the same time, called Dream Machines. By the time he completed each of them, in 1974, ARPANET had been released, and his vision for Project Xanadu had evolved. He published the two works together—Computer Lib was his lamentation over the industry’s disdain for hypertext, and Dream Machines was Xanadu’s manifesto. Nelson designed and printed the book himself. Its pages mostly look like this: Self-referential, multimedia, creative, and fun—they were a blueprint for the internet he was building. In the Dream Machines half, Nelson writes, “The real dream is for ‘everything’ to be in the hypertext. Everything you read, you read from the screen (and can always get back to right away; everything you write, you write at the screen (and can cross-link to whatever you read).” In one section Nelson asks himself, “Can It Be Done?” His answer: “I dunno.” Remember, Xanadu wouldn’t only involve links between works—it required hyperlinks, which as Nelson understood them, would need to contain the targets in themselves. (Eventually, Nelson would give these embeddings a new name—“transclusions”—and hyperlink came to simply mean “link between hypertext files.”) Every link would run both ways, each hypertext file would know exactly which other files were linked to it and how. This introduced a few problems, in the new interconnected ARPANET age: How do you keep track? Where’s the metadata stored? Can you afford enough space for it all?
“About six years later they started building computers like this at Xerox PARC.” Around the same time, Nelson claims to have called Vannevar Bush and told him about Project Xanadu. Bush “wanted very much to discuss it with” Nelson, but Nelson “hated him instantly [because] he sounded like a sports coach” and never contacted him again. This, of course, proved to be extremely self-destructive (though I can’t honestly say I would’ve done otherwise). Because Xanadu was as good as dead. No one would give him the money he needed to work on it, especially not after Doug Engelbart poisoned the idea of hypertext. Nelson went where there was funding, working briefly on an early word processor called Juggler of Text (JOT). …And then he lost investment, stopped working on the project, and moved to Chicago, where he’d been offered a job teaching at the University of Illinois, to start work on a book. He would call it Computer Lib. In fact, he started work on another book at the same time, called Dream Machines. By the time he completed each of them, in 1974, ARPANET had been released, and his vision for Project Xanadu had evolved. He published the two works together—Computer Lib was his lamentation over the industry’s disdain for hypertext, and Dream Machines was Xanadu’s manifesto. Nelson designed and printed the book himself. Its pages mostly look like this: Self-referential, multimedia, creative, and fun—they were a blueprint for the internet he was building. In the Dream Machines half, Nelson writes, “The real dream is for ‘everything’ to be in the hypertext. Everything you read, you read from the screen (and can always get back to right away; everything you write, you write at the screen (and can cross-link to whatever you read).” In one section Nelson asks himself, “Can It Be Done?” His answer: “I dunno.” Remember, Xanadu wouldn’t only involve links between works—it required hyperlinks, which as Nelson understood them, would need to contain the targets in themselves. (Eventually, Nelson would give these embeddings a new name—“transclusions”—and hyperlink came to simply mean “link between hypertext files.”) Every link would run both ways, each hypertext file would know exactly which other files were linked to it and how. This introduced a few problems, in the new interconnected ARPANET age: How do you keep track? Where’s the metadata stored? Can you afford enough space for it all?
Xanadu editor

Xanadu editor is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between September 19, 2025 and September 19, 2025. The archive places it in contexts such as "How ugly is that design! ... to write in a Xanadu editor". It most often appears alongside 1987, 1988, Adleman.

Reference entry
Xanadu editor
Mention count
1
Issue count
1
First seen
September 19, 2025
Last seen
September 19, 2025
September 19, 2025 · Original source
Maybe it looks a little unnatural, what you see when you squint at Xanadu—what a pain it would be to write in a Xanadu editor, you think. How ugly is that design!
xHamster

xHamster is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2021 and June 23, 2021. The archive places it in contexts such as "Porn site xHamster surveys 15,000 viewers". It most often appears alongside Arizona, Atlanta Black Crackers, Atlanta Crackers.

Reference entry
xHamster
Mention count
1
Issue count
1
First seen
June 23, 2021
Last seen
June 23, 2021
June 23, 2021 · Original source
38: Porn site xHamster surveys 15,000 viewers to learn about the intersection between politics, sex, and porn. Again, the headlines write themselves:
Yankee Candle

Yankee Candle is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 03, 2021 and March 03, 2021. The archive places it in contexts such as "by measuring average number of stars in Yankee Candle reviews". It most often appears alongside 9-11, Argentina, Austin Allred.

Reference entry
Yankee Candle
Mention count
1
Issue count
1
First seen
March 03, 2021
Last seen
March 03, 2021
March 03, 2021 · Original source
33: Coronavirus can cause loss of smell. A post on Tumblr claims you can track the course of the coronavirus pandemic by measuring average number of stars in Yankee Candle reviews - during peaks in infection, there are lots of bad reviews saying the candles have no scent.
Yuri

Yuri is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between February 03, 2022 and February 03, 2022. The archive places it in contexts such as "Yuri is a portable urinal that sits next to a bed"; "I am a programmer-turned-maker working on Yuri full-time". It most often appears alongside 538, 55-gal drum, 750k horny men.

Reference entry
Yuri
Mention count
1
Issue count
1
First seen
February 03, 2022
Last seen
February 03, 2022
February 03, 2022 · Original source
#39: Portable Urinal For Disabled Adults 1 in 3 adults over 30 wake two or more times to pee each night, and 70% of them are bothered by this. 1 in 7 US adults have a mobility disability. Yuri is a portable urinal that sits next to a bed, couch, or desk to eliminate wakeful or painful walks to the bathroom. It is a funnel, drain trap, and vented holding tank on wheels, and it does not smell. Emptying is infrequent, and is done by a graywater pump that connects to the tank and empties into an existing drain, like a sink, toilet, or shower. Yuri could help a lot of people who don’t move well in the 70%+ of voidings that are urine-only. My name is Matt Voda, and I am a programmer-turned-maker working on Yuri full-time. I’ve prototyped five versions of it so far and am close to an MVP. Future paths include a scaled-up, ruggedized version built around a 55-gal drum for places and people without plumbing, and a Roomba-esque wheelbase and docking station capable of pumping itself empty. Seeking mentors who can advise on the industrial design of the unit, how to engineer it for manufacturing, and the development and compliance of medical devices. Please also reach out if you or a loved one want to receive a unit at-cost in exchange for feedback on how to improve it. Email m@ttvoda.com
Zbioti

Zbioti is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 07, 2023 and December 07, 2023. The archive places it in contexts such as "Some are almost as creative as Lumina: Zbioti". It most often appears alongside Aaron, Aaron Silverbook, Aella.

Reference entry
Zbioti
Mention count
1
Issue count
1
First seen
December 07, 2023
Last seen
December 07, 2023
December 07, 2023 · Original source
The FDA has lower standards for probiotics than for drugs. And technically, a bacterium which you take in order to change your natural microbiome is a probiotic. The genetic modifications are no disqualification; a few genetically-modified probiotics have already been approved. Some are almost as creative as Lumina: Zbiotics is a genetically engineered Bacillus species which sits in your stomach and (supposedly; I have not investigated this claim) prevents hangovers by metabolizing alcohol byproducts for you.
Zbiotics

Zbiotics is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between December 07, 2023 and December 07, 2023. The archive places it in contexts such as "Zbiotics is a genetically engineered Bacillus species which sits in your stomach". It most often appears alongside Aaron, Aaron Silverbook, Aella.

Reference entry
Zbiotics
Mention count
1
Issue count
1
First seen
December 07, 2023
Last seen
December 07, 2023
December 07, 2023 · Original source
The FDA has lower standards for probiotics than for drugs. And technically, a bacterium which you take in order to change your natural microbiome is a probiotic. The genetic modifications are no disqualification; a few genetically-modified probiotics have already been approved. Some are almost as creative as Lumina: Zbiotics is a genetically engineered Bacillus species which sits in your stomach and (supposedly; I have not investigated this claim) prevents hangovers by metabolizing alcohol byproducts for you.
Zepbound®

Zepbound® is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 12, 2025 and March 12, 2025. The archive places it in contexts such as "Tirzepatide (Mounjaro®, Zepbound®)". It most often appears alongside Denmark, DOGE, Eli Lilly.

Reference entry
Zepbound®
Mention count
1
Issue count
1
First seen
March 12, 2025
Last seen
March 12, 2025
March 12, 2025 · Original source
Tirzepatide (Mounjaro®, Zepbound®)
Zillow

Zillow is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between June 23, 2022 and June 23, 2022. The archive places it in contexts such as "one from Kiplinger, one from Zillow". It most often appears alongside 1978, 2016 essay, A Resounding Success Or Disastrous Failure: Re-examining The Interpretation Of Evidence On The Portuguese Decriminalisation Of Illicit Drugs.

Reference entry
Zillow
Mention count
1
Issue count
1
First seen
June 23, 2022
Last seen
June 23, 2022
June 23, 2022 · Original source
I was suspicious of using a state-based analysis to talk about cities, so I repeated her work with the 50 biggest US cities, using two different sets of price data - one from Kiplinger, one from Zillow. I found the Zillow numbers a little more plausible; here they are: This was slightly lower, r^2 = 0.42, but still pretty good! I also don’t think my city homelessness data were perfect (people report homelessness data not by city but by “continuum of care area”, and it’s complicated to figure out what the overall population of each area is), so it wouldn’t surprise me if that’s responsible for most of the decay from Alyssa’s analysis to mine. Here you can see that San Francisco has a pretty high homelessness rate, but no worse than some other big cities like DC, Boston, and New York (Shellenberger, to his credit, mentions this in the book). So how come everyone talks about SF all the time? Alyssa gives two main reasons. First, SF homeless tend to concentrate in a few areas downtown; this is also where a lot of the tourists and businesspeople are, so the average tourist or businessperson in San Francisco sees a lot more homeless people than they would if they were evenly distributed throughout the city. And second, SF homeless are less likely to be sheltered than homeless people elsewhere; Shellenberger notes that “over 99% of New York’s homeless have access to shelter. In San Francisco, just 42% do” (see here for other cities). Source is here; I think “street homeless” means the same as “unsheltered” We’ll talk more in Part 4 about why this might be, but one common theory is climate: San Francisco has year-round above-freezing temperatures, so there’s less urgency to shelter everyone. Alyssa shows that the relationship between temperature and percent unsheltered is strong: That regression line looks suspicious, but I hear computers are never wrong. So one possible conclusion is that SF has around the amount of homelessness you would predict from its very high housing prices, and around the percent unsheltered you would predict from its balmy winter weather, and there’s nothing further to be explained. Shellenberger does not like this conclusion. San Francisco’s mild climate alone cannot explain why it has more homeless people than other cities. Miami, Phoenix, and Houston have year-round warm weather and far fewer homeless than San Francisco per capita. Per capita homelessness in San Francisco, Greater Miami, Greater Phoenix, and Greater Houston in 2020 was 9.3, 1.3, 1.6, and 0.8 per 1,000 residents, respectively. And Greater Miami, Greater Phoenix, and Greater Houston saw their per capita homeless population decline from 2005 to 2020 by 39, 17, and 74 percent while San Francisco saw its rise 30 percent. Nor can housing prices explain the discrepancy. Palo Alto and Beverly Hills have mild climates and expensive housing but don’t have San Francisco’s homeless problem. As for the Zillow study that was reported to find a correlation between rising rents and homelessness, a deeper look at the research reveals a more nuanced finding. Homelessness and affordability are correlated only in the context of certain “local policy efforts [and] social attitudes,” concluded researchers. This feels like kind of a shell game. San Francisco’s mild climate alone can’t explain why it has more homeless people per capita than Miami or Houston. But as the graph above shows, housing prices do explain about 75% of the difference between SF and those two cities. But because the book talks about the Miami-SF discrepancy in the paragraph about climate instead of the paragraph about prices, it makes it sound like a mystery that neither prices nor climate can explain. The Zillow article mentioned is Homelessness Rises Faster Where Rents Exceed A Third Of Incomes, which is based on this study. Shellenberger’s summary is not really the researchers’ conclusion. The article does mention “local attitudes” and “social policy” once, but only to explain that the paper includes a term representing “latent factors” that they’re not going to bother distinguishing from each other in their model, and some of those terms could be local policy or social attitudes. Later they mention there are some outliers in their model (eg Houston), and it would be reasonable to assume that the latent factors help explain the outliers, but they don’t give us any reason to think that this is more interesting than the fact that every model ever will have outliers. But also, this is one study by Zillow. Alyssa and I both tried the same analysis, and found the same thing, with a correlation that’s unusually high for this kind of work. Sure, there are outliers, but San Francisco isn’t one of them. San Francisco is only a couple of percent off where the regression line would predict. That leaves the point about Palo Alto and Beverly Hills. They “have mild climates and expensive housing but don’t have San Francisco’s homeless problem”. At first I felt like this was cheating - yeah, rich suburbs don’t have lots of homelessness, come on. But “rich” and “high property values” are pretty close to synonyms. If you’re going to say that high property values cause homelessness, isn’t it in fact pretty surprising that rich suburbs don’t have it? In fact, if you’re a homeless person, why wouldn’t you want to live in a suburb? Quieter (so probably easier to sleep at night) more places out of sight to pitch tents, less crime (important if you’re living on the street!), and potentially lower cost of living in terms of food and goods. I tried looking into this issue and found explanations like: Usually it’s poor people who become homeless. Cities have more poor people than suburbs, because they have more rental units, small apartments, public transportation, and blue-collar jobs. Suburbs, by natural consequence of their layout, enforce a certain wealth minimum before people can live there, and people above that wealth minimum rarely lose everything and become homeless. It’s strange that poor people tend to live in cities (ie places with very high land values), and you have to wonder whether there are ways that could be different, but it does seem true.
That regression line looks suspicious, but I hear computers are never wrong. So one possible conclusion is that SF has around the amount of homelessness you would predict from its very high housing prices, and around the percent unsheltered you would predict from its balmy winter weather, and there’s nothing further to be explained. Shellenberger does not like this conclusion. San Francisco’s mild climate alone cannot explain why it has more homeless people than other cities. Miami, Phoenix, and Houston have year-round warm weather and far fewer homeless than San Francisco per capita. Per capita homelessness in San Francisco, Greater Miami, Greater Phoenix, and Greater Houston in 2020 was 9.3, 1.3, 1.6, and 0.8 per 1,000 residents, respectively. And Greater Miami, Greater Phoenix, and Greater Houston saw their per capita homeless population decline from 2005 to 2020 by 39, 17, and 74 percent while San Francisco saw its rise 30 percent. Nor can housing prices explain the discrepancy. Palo Alto and Beverly Hills have mild climates and expensive housing but don’t have San Francisco’s homeless problem. As for the Zillow study that was reported to find a correlation between rising rents and homelessness, a deeper look at the research reveals a more nuanced finding. Homelessness and affordability are correlated only in the context of certain “local policy efforts [and] social attitudes,” concluded researchers. This feels like kind of a shell game. San Francisco’s mild climate alone can’t explain why it has more homeless people per capita than Miami or Houston. But as the graph above shows, housing prices do explain about 75% of the difference between SF and those two cities. But because the book talks about the Miami-SF discrepancy in the paragraph about climate instead of the paragraph about prices, it makes it sound like a mystery that neither prices nor climate can explain. The Zillow article mentioned is Homelessness Rises Faster Where Rents Exceed A Third Of Incomes, which is based on this study. Shellenberger’s summary is not really the researchers’ conclusion. The article does mention “local attitudes” and “social policy” once, but only to explain that the paper includes a term representing “latent factors” that they’re not going to bother distinguishing from each other in their model, and some of those terms could be local policy or social attitudes. Later they mention there are some outliers in their model (eg Houston), and it would be reasonable to assume that the latent factors help explain the outliers, but they don’t give us any reason to think that this is more interesting than the fact that every model ever will have outliers. But also, this is one study by Zillow. Alyssa and I both tried the same analysis, and found the same thing, with a correlation that’s unusually high for this kind of work. Sure, there are outliers, but San Francisco isn’t one of them. San Francisco is only a couple of percent off where the regression line would predict. That leaves the point about Palo Alto and Beverly Hills. They “have mild climates and expensive housing but don’t have San Francisco’s homeless problem”. At first I felt like this was cheating - yeah, rich suburbs don’t have lots of homelessness, come on. But “rich” and “high property values” are pretty close to synonyms. If you’re going to say that high property values cause homelessness, isn’t it in fact pretty surprising that rich suburbs don’t have it? In fact, if you’re a homeless person, why wouldn’t you want to live in a suburb? Quieter (so probably easier to sleep at night) more places out of sight to pitch tents, less crime (important if you’re living on the street!), and potentially lower cost of living in terms of food and goods. I tried looking into this issue and found explanations like: Usually it’s poor people who become homeless. Cities have more poor people than suburbs, because they have more rental units, small apartments, public transportation, and blue-collar jobs. Suburbs, by natural consequence of their layout, enforce a certain wealth minimum before people can live there, and people above that wealth minimum rarely lose everything and become homeless. It’s strange that poor people tend to live in cities (ie places with very high land values), and you have to wonder whether there are ways that could be different, but it does seem true.
Zoloft

Zoloft is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between March 31, 2021 and March 31, 2021. The archive places it in contexts such as "The most effective dose of every SSRI would be: Zoloft: 75 mg". It most often appears alongside ASRI, Celexa, Cipriani.

Reference entry
Zoloft
Mention count
1
Issue count
1
First seen
March 31, 2021
Last seen
March 31, 2021
March 31, 2021 · Original source
Prozac: 30 mg Paxil: 30 mg Zoloft: 75 mg Celexa: 30 mg Lexapro: 15 mg
Zolpidem

Zolpidem is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between May 31, 2023 and May 31, 2023. The archive places it in contexts such as "Zolpidem ("Ambien") has effect size around 0.39". It most often appears alongside anticholinergics, benzodiazepines, bisphosphonates.

Reference entry
Zolpidem
Mention count
1
Issue count
1
First seen
May 31, 2023
Last seen
May 31, 2023
May 31, 2023 · Original source
This doesn’t even include some of my favorites. Zolpidem (“Ambien”) has effect size around 0.39 for getting you to sleep faster. Ibuprofen (“Advil”, “Motrin”) has effect sizes between from about 0.20 (for surgical pain) to 0.42 (for arthritis). All of these are around the 0.30 effect size of antidepressants. There’s no anti-ibuprofen lobby trying to rile people up about NSAIDs, so nobody’s pointed out that this is “clinically insignificant”. But by traditional standards, it is!
Statisticians have tried to put effect sizes in context by saying some effect sizes are “small” or “big” or “relevant” or “miniscule”. I think this is a valiant effort. But it makes things worse as often as it makes them better. Some effect sizes are smaller than we think; others are larger. Consider a claim that the difference between treatment and control groups was “only as big, in terms of effect size, as the average height difference between men and women - just a couple of inches” (I think I saw someone say this once, but I’ve lost the reference thoroughly enough that I’m presenting it as a hypothetical). That drug would be more than four times stronger than Ambien! The difference between study effect sizes, population effect sizes, and individual effect sizes only confuses things further.
Zoox

Zoox is a recurring brand in the Astral Codex Ten archive, appearing 1 times across 1 issues between October 24, 2024 and October 24, 2024. The archive places it in contexts such as "Amazon’s self-driving car, Zoox, looks like this". It most often appears alongside 1960: The Year The Singularity Was Cancelled, 1960s, 1973.

Reference entry
Zoox
Mention count
1
Issue count
1
First seen
October 24, 2024
Last seen
October 24, 2024
October 24, 2024 · Original source
Amazon’s self-driving car, Zoox, looks like this (source). It’s not private pods yet, but it’s proof that self-driving gives you the opportunity to experiment with form. Here the person I talked to wasn’t as concerned about fighting destructive regulation (which mostly has yet to materialize) as using legislation to guide the technology on the right path. Self-driving taxis have a big advantage over self-driving self-owned-cars: they can operate 24-7 and never have to park. If you can switch half the car-using population to robotaxis, you can convert half the parking lots into green space or homes. Nobody wants to ban self-driving car ownership, but some people do want to nudge the marginal commuter into robotaxis so they can reclaim slightly-more-than-half of the parking lots instead of slightly-less.