Astral Codex Ten

anorexia

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anorexia

Article

anorexia is a recurring concept in the Astral Codex Ten archive, appearing 3 times across 3 issues between July 21, 2021 and July 31, 2025. The archive places it in contexts such as “If you think of (anorexia and conversion disorder) as two ‘symptoms’ of some underlying nameless illness”; “maybe other things like anorexia . And maybe it works for some people”; “increased anorexia risk from raising IQ”. It most often appears alongside Scott, US, 23andMe.

Metadata

  • Category: Concepts
  • Mention count: 3
  • Issue count: 3
  • First seen: July 21, 2021
  • Last seen: July 31, 2025

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Highlights From The Comments On "Crazy Like Us"
July 21, 2021 · Original source
The part where this becomes confusing is I guess where you draw the boundaries of mental illness. If you think of (anorexia and conversion disorder) as two “symptoms” of some underlying nameless illness, then maybe some places will have conversion disorder (but no anorexia) and other places will have anorexia (but no conversion disorder), and then it will look like Westerners “brought” anorexia to a place that was previously anorexia-free. The only problem with this way of looking at things is that if true, you would expect some other illness (in this case, conversion disorder) to decrease at the same time anorexia increased, and I don’t know of any research on whether this happened or not.
Highlights From The Comments On Semaglutide
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)
Inline links: here, here, here, here, here, writes, Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, writes, writes, anorexia, writes, Education Realist, blog, https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro, writes, writes, from Walter, Why can’t people just diet and exercise?
Suddenly, Trait-Based Embryo Selection
July 31, 2025 · Original source
That serves as proof-of-concept that this technology can work, and means other companies’ claims are at least plausible. Scientific Objections: Antagonistic Pleiotropy This is a fancy term for “sometimes genes that are good in one way are bad in other ways”. For example, there is a gene that decreases the risk of lung cancer, but increases the risk of leukemia. If you selected against lung cancer, you might give your child higher leukemia risk. Several of the professional societies raise this concern, and Sasha Gusev gives several examples here, including a correlation between education/IQ and anorexia. When I think about these concerns, I consider the following thought experiment: suppose that I had a natural, unselected child, and that child became high school valedictorian and got into Harvard. Would my first reaction be “Oh no! This slightly raises her risk of anorexia!”? If not, why should this be our reaction to artificially increasing IQ? Genetic selection isn’t doing some different, magical thing. It’s just picking from within the natural IQ/anorexia variation. If you would be happy to have higher IQ (or lower breast cancer risk, or lower schizophrenia risk) naturally, you should be happy to get it through selection too. (Objection one: suppose that the genetic component of IQ is net negative, but the environmental component is net positive to an even greater degree. Then IQ itself might be net positive - so you could still celebrate your valedictorian child - but since the genetic component alone is bad you wouldn’t want to select for it. I have never heard anyone seriously claim this, most studies suggest that genetic components of good things are good in the expected ways, and most critics don’t get this far. I mention it for the sake of completeness only.) (Objection two: is the example above just saying that I value IQ more than non-anorexia? If so, couldn’t I give an alternate example of learning that my child isn’t anorexic, celebrating this seemingly-obviously-good fact, but actually this means they have lower IQ and based on my stated values I should be sad? I don’t think so. There is no claim that the increased anorexia risk from raising IQ is exactly as bad as the IQ increase is good - for example, you could imagine a world where going from moron to supergenius only raises anorexia risk 0.0001%. More generally - although not rigorously - selecting for X should usually increase X more than it increases tangentially-correlated construct Y. So selecting for IQ should be net positive, even though it might slightly increase anorexia risk, and selecting for anorexia should be net negative, even though it might slightly increase IQ. I think this is the intuition that drives parents to be happy both when they learn that their child is smart, and when they learn their child doesn’t have anorexia - not just an intuition that one trait matters more than the other) But also, here’s the table of correlated genetic risks for psychiatric disorders: …where blue means that lowering the risk of one disease also lowers the risk of the other, and red means the opposite (as in the IQ - anorexia example above). Here’s the same table for other conditions, courtesy of Genomic Prediction (except I flipped the colors from the original, to match the one above): Aside from two bright orange squares (gallstones vs. hypertension and hypothyroidism - I don’t know what’s up with this and it doesn’t seem to be a widely-appreciated result) we see that most correlations are zero or positive - that is, selecting against one disease selects against another or at worst does nothing. In this ocean of blue, worrying about those few orange squares feels a bit motivated. Hans Jonas-ism says that no medical intervention may ever cause any harm, no matter how much benefit it produces. By this standard, perhaps slightly raising the risk of gallstones in the process of preventing various cancers and psychoses and other forms of human misery is unacceptable. To anyone with the more normal perspective where something with large benefits and tiny downsides is still pretty good, I don’t think the antagonistic pleiotropy argument carries much weight. Ethical Objection: Cost No way around this one: if these products work, they mean that rich people can have healthier/smarter/taller/prettier kids than poor people. One might object that at least they’re in good company: other products which help rich kids get healthier/smarter/taller/prettier than poor kids include private tutors, gyms, hair salons, health insurance, clothing, books, and food. Is this really the time to declare ourselves against this kind of thing? But maybe we should fight against expanding this already-bloated category. Or maybe there’s something more final about a genetic advantage. Maybe a stronger argument is that rich people get first crack at every new technology, but poor people usually follow close behind. The first cellphone, in 1982, cost $12,000 in today’s dollars. Now you can get something a thousand times better for $50, and Kenyan pastoralists use cell phones to call up the local shaman. The trajectory of genetics has been even more striking: sequencing a single genome cost about $100 million in 2000 and is somewhere around $100 today. Polygenic embryo selection has the potential to follow a similar path. There are two associated costs - sequencing the embryos, and running the analysis. Sequencing costs are decreasing and may eventually be comparable to the sorts of genetic screening (for e.g. Down Syndrome) that most families get anyway. Analysis costs are mostly the one-time expense of inventing the predictor; we might expect these to follow the same pattern as generic medications, where cutting-edge technology is jealously guarded and expensive, but last decade’s technology has made its way off patent and is cheap-to-free. A few groups have already created free open-source predictors; so far these are much worse than the private companies’ versions, but one of last year’s ACX Grantees is working on a better one. Also, it would be crazy for any forward-thinking government not to cover this; it could save hundreds of thousands of dollars in future health care expenses. In countries with public health care, this comes directly out of the government treasury; even in the US, it’s covered by Medicare after age 65. The government should be begging people to select embryos. The most persistent cost barrier is likely to be in vitro fertilization itself, a necessary precursor. In the US, 2-3% of babies are born through IVF. For those kids, this is a no-brainer - even if the cost never comes down, the cheaper products are only a fraction of total IVF expense. What about the other 98%? If those parents feel like they have to get embryo selection (and therefore IVF) to keep up, this could be a significant burden. IVF isn’t fun - it requires pumping a woman full of mind-altering hormones for weeks, extracting eggs in a minor surgery, and then implanting embryos in another minor surgery, all with a decent chance that some step will fail and you’ll have to do it all again. It also costs $15,000 in the US (less in poorer countries), and unlike the genetics, the cost has barely gone down in the past twenty-five years. Some countries, including Israel, offer free IVF for anybody who wants it. And universal basic IVF is surprisingly popular even in the usually government-phobic United States - Donald Trump made it part of his campaign platform. So there’s a plausible path to embryo selection for everyone who wants it. But it’s still going to take a while, it will hit different people at different times, and so far11 there’s no way around the month or two of various miserable medical procedures for women. Ethical Objection: Personhood Is it really correct to say that you have reduced someone’s risk of breast cancer by 46%, if what you’ve really done is closer to replacing them with a different person who is 46% less likely to have breast cancer? I cover this one in more depth here. Ethical Objection: Race This one is awkward: right now the technology works best for white people. Most genetic data available for research/commercial use comes from the UK, US, and Europe - areas which are mostly white. Asian biobanks, and those serving US minority communities, have been more reluctant to share data. So we know a lot about the genetics of white people, and only a limited amount about the genetics of anyone else. Companies are suitably embarrassed about this, and researchers in the field are working hard to wring every ounce of information out of the minority data they have. But for now, white people are the clear winner. Here’s data from Herasight: A European family with five embryos and no family history can cut their diabetes risk by 47%, and an African family 29%, with everyone else in between. As usual, all companies say that they adjust their scores based on the couple’s genetic ancestry. As usual, Herasight challenges them to publicly release data on exactly how they performed the adjustments and how well they work. All companies say they are working as hard as they can to improve cross-ancestry portability, but that progress will remain limited until governments collect/release better genetic data on non-white populations. Ethical Objection: Selection At some point, you’ve got to choose. Genomic Prediction and Herasight offer scores that aggregate overall health risks. Some people will follow them slavishly. Other people will try to second-guess them - would you prefer your child have lower cancer risk, or less chance of heart attacks? And this is the best case scenario! Herasight offers predictors for IQ, height and BMI; Nucleus offers those plus eye color and hair color12. A parent might encounter a situation where the embryo with their favorite eye color also has the highest cancer and schizophrenia risk, and choose to doom their child to cancer and schizophrenia because they really want pretty eyes. On average, even if everyone in the world selected for eye color, it wouldn’t raise cancer and schizophrenia risk. No not-deliberately-perverse polygenic selection choice can make your child worse off in expectation. Still, suppose you got cancer, and your mom admitted that she selected you for pretty eyes and didn’t even check the cancer column of the embryo selection report. How would you feel? And would you feel better or worse than someone whose parents didn’t do embryo selection at all, and spent the money on a Caribbean vacation? What if they selected your brother for everything great, then had you naturally? What if they selected you for IQ, but actually you are very stupid, and you were one of the 20% of cases where a predictor that’s right 80% of the time gets it wrong? Mark my words, one day there will be entire subfields of therapy dedicated to these issues. Going Nuclear Even as outsiders criticize the whole field, Herasight has launched a full-scale attack on competitor Nucleus. Herasight’s white paper compares its own predictors (favorably) to those of Orchid and Genomic Prediction… …but refuses to acknowledge Nucleus at all. In a supplementary note, the authors explain why: they accuse Nucleus of being so bad that it would “not yield a reliable or meaningful addition to our analysis”. They say Nucleus has inflated the accuracy of their scores. This is most dramatic for a few conditions like ADHD, where the leading published polygenic score is based on 2,300,000 variants but explains only ~1% of variance in the condition. Nucleus’ score is based on 12 variants13 and (implicitly) claims to explain 3-6%. This doesn’t make sense. Some of Nucleus’ other scores do use millions of variants. But many of these are 5-10 year old scores downloaded from open-source catalogs, whose accuracy statistics are easily available and far less than Nucleus claims. Here is what Herasight finds when they double-check Nucleus’ numbers: On their Substack, Herasight also criticizes Nucleus’ monogenic screening product. They point out cases where it fails to properly screen for the conditions it claims. For example, the Nucleus website advertises screening for spinal muscular atrophy: But on their gene list… …they don’t screen for SMN, which causes 95% of spinal muscular atrophy cases. They only screen for UBA1, which causes a distinct and much rarer condition called x-linked infantile spinal muscular atrophy. Professional organizations publish guidelines for what genes need to be screened in a screening product, and Nucleus does not appear to be following them. In further discussion, Herasight continued with exhaustive criticism of essentially everything Nucleus had ever done down to the smallest detail. Nucleus reports list the same baseline disease risk regardless of patient ancestry, but different ancestry groups should have different risks14. Nucleus’ physician reports sometimes list lower-than-average risk for patients with positive polygenic scores15. Nucleus’ age-based risk tables don’t distinguish between age and cohort effects (is this bad? see footnote16). My favorite critique is that Nucleus wrote a blog post criticizing competing company Orchid… …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. $53,250 Herasight cost). 9As part of researching this article, I asked all four major companies about their within-family validation strategies. Here are some details: Genomic Prediction discusses their strategy in this paper. The results are complicated to interpret - the within-family numbers often have such wide error bars that they overlap with both the across-family numbers and with zero - but looking qualitatively it seems like most scores on average lose about 25% of their risk reduction ability (though averages might not be the right way to do this, and some might be much more affected than others). Their website reports unadjusted, not within-family validated numbers; GP says they say this clearly on their site (which is true), Herasight counters that they still present their numbers as applicable to embryo selection (which is also true). To get the most applicable-to-embryo-selection numbers, you might want to adjust GP’s stated numbers down somewhat; it’s hard to say exactly how much, but maybe 20 - 25%?
Inline links: here, here’s, https://substackcdn.com/image/fetch/$s_!G_Lu!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F7049550b-4253-4900-9fe1-9f2df009e829_446x432.png, Here’s the same table for other conditions, https://substackcdn.com/image/fetch/$s_!jscV!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F9a3ad311-4745-4f16-b82a-7ccdb297c670_1239x1600.png, Hans Jonas-ism, somewhere around $100 today., Donald Trump made it part of his campaign platform, 11, here, https://substackcdn.com/image/fetch/$s_!1Alk!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F1af69f39-f353-4aa6-acb9-d8c3b05c7bac_728x895.jpeg, 12, Herasight’s white paper, https://substackcdn.com/image/fetch/$s_!S7lY!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F738260ba-8fe2-4647-8ca2-eeb4d13e0fce_605x341.png, 13, https://substackcdn.com/image/fetch/$s_!u7YE!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F451c286b-c677-47af-8c07-f0d993a14384_612x345.png, their Substack, the Nucleus website, https://substackcdn.com/image/fetch/$s_!XmL4!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff77915b4-3b36-4908-8f9f-032b7cf865ff_562x432.png, https://substackcdn.com/image/fetch/$s_!bxjb!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2df9ffe5-17a3-4448-9a20-e9b27ac9a519_1250x795.png, publish guidelines, 14, 15, 16, a blog post criticizing competing company Orchid, https://substackcdn.com/image/fetch/$s_!MZCB!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2cf9cbf4-825b-4373-9052-80e43c36febf_718x1035.png, 17, GLP-1RAs, O-ring technologies, things in the pipeline, everybody, nobody, 1, 2, their risk calculator, everything, here, https://substackcdn.com/image/fetch/$s_!jtkY!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fd645c392-fed1-4f02-9a2e-878b8c7ef7f2_909x878.png, 3, 4, 5, 6, 7, https://substackcdn.com/image/fetch/$s_!Vimq!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fca0f1f15-268d-465a-a70f-b7f1173c6111_566x166.png, https://substackcdn.com/image/fetch/$s_!3B0A!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Faccc7a65-b142-4bf6-927d-53eb607d71ef_552x155.png, 8, 9
…where blue means that lowering the risk of one disease also lowers the risk of the other, and red means the opposite (as in the IQ - anorexia example above). Here’s the same table for other conditions, courtesy of Genomic Prediction (except I flipped the colors from the original, to match the one above): Aside from two bright orange squares (gallstones vs. hypertension and hypothyroidism - I don’t know what’s up with this and it doesn’t seem to be a widely-appreciated result) we see that most correlations are zero or positive - that is, selecting against one disease selects against another or at worst does nothing. In this ocean of blue, worrying about those few orange squares feels a bit motivated. Hans Jonas-ism says that no medical intervention may ever cause any harm, no matter how much benefit it produces. By this standard, perhaps slightly raising the risk of gallstones in the process of preventing various cancers and psychoses and other forms of human misery is unacceptable. To anyone with the more normal perspective where something with large benefits and tiny downsides is still pretty good, I don’t think the antagonistic pleiotropy argument carries much weight. Ethical Objection: Cost No way around this one: if these products work, they mean that rich people can have healthier/smarter/taller/prettier kids than poor people. One might object that at least they’re in good company: other products which help rich kids get healthier/smarter/taller/prettier than poor kids include private tutors, gyms, hair salons, health insurance, clothing, books, and food. Is this really the time to declare ourselves against this kind of thing? But maybe we should fight against expanding this already-bloated category. Or maybe there’s something more final about a genetic advantage. Maybe a stronger argument is that rich people get first crack at every new technology, but poor people usually follow close behind. The first cellphone, in 1982, cost $12,000 in today’s dollars. Now you can get something a thousand times better for $50, and Kenyan pastoralists use cell phones to call up the local shaman. The trajectory of genetics has been even more striking: sequencing a single genome cost about $100 million in 2000 and is somewhere around $100 today. Polygenic embryo selection has the potential to follow a similar path. There are two associated costs - sequencing the embryos, and running the analysis. Sequencing costs are decreasing and may eventually be comparable to the sorts of genetic screening (for e.g. Down Syndrome) that most families get anyway. Analysis costs are mostly the one-time expense of inventing the predictor; we might expect these to follow the same pattern as generic medications, where cutting-edge technology is jealously guarded and expensive, but last decade’s technology has made its way off patent and is cheap-to-free. A few groups have already created free open-source predictors; so far these are much worse than the private companies’ versions, but one of last year’s ACX Grantees is working on a better one. Also, it would be crazy for any forward-thinking government not to cover this; it could save hundreds of thousands of dollars in future health care expenses. In countries with public health care, this comes directly out of the government treasury; even in the US, it’s covered by Medicare after age 65. The government should be begging people to select embryos. The most persistent cost barrier is likely to be in vitro fertilization itself, a necessary precursor. In the US, 2-3% of babies are born through IVF. For those kids, this is a no-brainer - even if the cost never comes down, the cheaper products are only a fraction of total IVF expense. What about the other 98%? If those parents feel like they have to get embryo selection (and therefore IVF) to keep up, this could be a significant burden. IVF isn’t fun - it requires pumping a woman full of mind-altering hormones for weeks, extracting eggs in a minor surgery, and then implanting embryos in another minor surgery, all with a decent chance that some step will fail and you’ll have to do it all again. It also costs $15,000 in the US (less in poorer countries), and unlike the genetics, the cost has barely gone down in the past twenty-five years. Some countries, including Israel, offer free IVF for anybody who wants it. And universal basic IVF is surprisingly popular even in the usually government-phobic United States - Donald Trump made it part of his campaign platform. So there’s a plausible path to embryo selection for everyone who wants it. But it’s still going to take a while, it will hit different people at different times, and so far11 there’s no way around the month or two of various miserable medical procedures for women. Ethical Objection: Personhood Is it really correct to say that you have reduced someone’s risk of breast cancer by 46%, if what you’ve really done is closer to replacing them with a different person who is 46% less likely to have breast cancer? I cover this one in more depth here. Ethical Objection: Race This one is awkward: right now the technology works best for white people. Most genetic data available for research/commercial use comes from the UK, US, and Europe - areas which are mostly white. Asian biobanks, and those serving US minority communities, have been more reluctant to share data. So we know a lot about the genetics of white people, and only a limited amount about the genetics of anyone else. Companies are suitably embarrassed about this, and researchers in the field are working hard to wring every ounce of information out of the minority data they have. But for now, white people are the clear winner. Here’s data from Herasight: A European family with five embryos and no family history can cut their diabetes risk by 47%, and an African family 29%, with everyone else in between. As usual, all companies say that they adjust their scores based on the couple’s genetic ancestry. As usual, Herasight challenges them to publicly release data on exactly how they performed the adjustments and how well they work. All companies say they are working as hard as they can to improve cross-ancestry portability, but that progress will remain limited until governments collect/release better genetic data on non-white populations. Ethical Objection: Selection At some point, you’ve got to choose. Genomic Prediction and Herasight offer scores that aggregate overall health risks. Some people will follow them slavishly. Other people will try to second-guess them - would you prefer your child have lower cancer risk, or less chance of heart attacks? And this is the best case scenario! Herasight offers predictors for IQ, height and BMI; Nucleus offers those plus eye color and hair color12. A parent might encounter a situation where the embryo with their favorite eye color also has the highest cancer and schizophrenia risk, and choose to doom their child to cancer and schizophrenia because they really want pretty eyes. On average, even if everyone in the world selected for eye color, it wouldn’t raise cancer and schizophrenia risk. No not-deliberately-perverse polygenic selection choice can make your child worse off in expectation. Still, suppose you got cancer, and your mom admitted that she selected you for pretty eyes and didn’t even check the cancer column of the embryo selection report. How would you feel? And would you feel better or worse than someone whose parents didn’t do embryo selection at all, and spent the money on a Caribbean vacation? What if they selected your brother for everything great, then had you naturally? What if they selected you for IQ, but actually you are very stupid, and you were one of the 20% of cases where a predictor that’s right 80% of the time gets it wrong? Mark my words, one day there will be entire subfields of therapy dedicated to these issues. Going Nuclear Even as outsiders criticize the whole field, Herasight has launched a full-scale attack on competitor Nucleus. Herasight’s white paper compares its own predictors (favorably) to those of Orchid and Genomic Prediction… …but refuses to acknowledge Nucleus at all. In a supplementary note, the authors explain why: they accuse Nucleus of being so bad that it would “not yield a reliable or meaningful addition to our analysis”. They say Nucleus has inflated the accuracy of their scores. This is most dramatic for a few conditions like ADHD, where the leading published polygenic score is based on 2,300,000 variants but explains only ~1% of variance in the condition. Nucleus’ score is based on 12 variants13 and (implicitly) claims to explain 3-6%. This doesn’t make sense. Some of Nucleus’ other scores do use millions of variants. But many of these are 5-10 year old scores downloaded from open-source catalogs, whose accuracy statistics are easily available and far less than Nucleus claims. Here is what Herasight finds when they double-check Nucleus’ numbers: On their Substack, Herasight also criticizes Nucleus’ monogenic screening product. They point out cases where it fails to properly screen for the conditions it claims. For example, the Nucleus website advertises screening for spinal muscular atrophy: But on their gene list… …they don’t screen for SMN, which causes 95% of spinal muscular atrophy cases. They only screen for UBA1, which causes a distinct and much rarer condition called x-linked infantile spinal muscular atrophy. Professional organizations publish guidelines for what genes need to be screened in a screening product, and Nucleus does not appear to be following them. In further discussion, Herasight continued with exhaustive criticism of essentially everything Nucleus had ever done down to the smallest detail. Nucleus reports list the same baseline disease risk regardless of patient ancestry, but different ancestry groups should have different risks14. Nucleus’ physician reports sometimes list lower-than-average risk for patients with positive polygenic scores15. Nucleus’ age-based risk tables don’t distinguish between age and cohort effects (is this bad? see footnote16). My favorite critique is that Nucleus wrote a blog post criticizing competing company Orchid… …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. $53,250 Herasight cost). 9As part of researching this article, I asked all four major companies about their within-family validation strategies. Here are some details: Genomic Prediction discusses their strategy in this paper. The results are complicated to interpret - the within-family numbers often have such wide error bars that they overlap with both the across-family numbers and with zero - but looking qualitatively it seems like most scores on average lose about 25% of their risk reduction ability (though averages might not be the right way to do this, and some might be much more affected than others). Their website reports unadjusted, not within-family validated numbers; GP says they say this clearly on their site (which is true), Herasight counters that they still present their numbers as applicable to embryo selection (which is also true). To get the most applicable-to-embryo-selection numbers, you might want to adjust GP’s stated numbers down somewhat; it’s hard to say exactly how much, but maybe 20 - 25%?
Inline links: Here’s the same table for other conditions, https://substackcdn.com/image/fetch/$s_!jscV!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F9a3ad311-4745-4f16-b82a-7ccdb297c670_1239x1600.png, Hans Jonas-ism, somewhere around $100 today., Donald Trump made it part of his campaign platform, 11, here, https://substackcdn.com/image/fetch/$s_!1Alk!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F1af69f39-f353-4aa6-acb9-d8c3b05c7bac_728x895.jpeg, 12, Herasight’s white paper, https://substackcdn.com/image/fetch/$s_!S7lY!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F738260ba-8fe2-4647-8ca2-eeb4d13e0fce_605x341.png, 13, https://substackcdn.com/image/fetch/$s_!u7YE!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F451c286b-c677-47af-8c07-f0d993a14384_612x345.png, their Substack, the Nucleus website, https://substackcdn.com/image/fetch/$s_!XmL4!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff77915b4-3b36-4908-8f9f-032b7cf865ff_562x432.png, https://substackcdn.com/image/fetch/$s_!bxjb!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2df9ffe5-17a3-4448-9a20-e9b27ac9a519_1250x795.png, publish guidelines, 14, 15, 16, a blog post criticizing competing company Orchid, https://substackcdn.com/image/fetch/$s_!MZCB!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F2cf9cbf4-825b-4373-9052-80e43c36febf_718x1035.png, 17, GLP-1RAs, O-ring technologies, things in the pipeline, everybody, nobody, 1, 2, their risk calculator, everything, here, https://substackcdn.com/image/fetch/$s_!jtkY!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fd645c392-fed1-4f02-9a2e-878b8c7ef7f2_909x878.png, 3, 4, 5, 6, 7, https://substackcdn.com/image/fetch/$s_!Vimq!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fca0f1f15-268d-465a-a70f-b7f1173c6111_566x166.png, https://substackcdn.com/image/fetch/$s_!3B0A!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Faccc7a65-b142-4bf6-927d-53eb607d71ef_552x155.png, 8, 9