Science

Article

Science is a recurring publication in the Astral Codex Ten archive, appearing 10 times across 10 issues between December 28, 2021 and October 17, 2025. The archive places it in contexts such as “has written pieces for Science”; “Nature , and Science . They both publish articles in all scientific fields”; “Science is only slightly younger, having been founded in 1880”. It most often appears alongside Nature, FDA, Scott.

Metadata

Category: Publications
Mention count: 10
Issue count: 10
First seen: December 28, 2021
Last seen: October 17, 2025

Appears In

- Nature (5 shared issues)
- FDA (4 shared issues)
- Scott (4 shared issues)
- ACX (3 shared issues)
- Cell (3 shared issues)
- China (3 shared issues)
- Substack (3 shared issues)
- Twitter (3 shared issues)
- Wikipedia (3 shared issues)
- ACX (2 shared issues)
- aducanumab (2 shared issues)
- Alzheimer’s (2 shared issues)

External Links

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.

ACX Grants Results

December 28, 2021 · Original source

The Segura Lab at Duke, $50,000, to continue work on materials that promote healthy tissue regrowth after stroke. They say their experiments are difficult to fund because regrowing dead brain tissue is a long shot that requires a lot of out of the box thinking and is hard to explain. If you want to learn more about their work, check out http://seguralab.duke.edu. If you’re a stroke survivor and want to share your story, they’d like you to check out their Patient Connection page. They’re also looking for help spreading their ideas. If you have knowledge of both science and writing/visual communication, apply to work with them here; if you want to donate, you can do so here.

Inline links: The Segura Lab, http://seguralab.duke.edu, Patient Connection page, here, here

Spencer Greenberg, $40,000, as seed money for his project to produce rapid replications of high-impact social science papers. Right now, when a new social science paper comes out, we often have to wait as long as several months to discover that it was false. Spencer and his team dream of a world where we can learn that almost immediately, soon enough that it's within the same news cycle and the journals involved feel kind of bad about it. This money will sponsor a pilot, after which he’ll be seeking additional funding - if you think you can help, you can reach him here. Spencer's been involved in rationality and EA about as long as either has existed, blogs at Optimize Everything, is the founder of ClearerThinking.org (which offers free digital tools related to rationality, decision-making and happiness) and runs the Clearer Thinking podcast, with guests including Daniel Kahneman, Tyler Cowen, and Sam Bankman-Fried.

Inline links: here, Optimize Everything, ClearerThinking.org, Clearer Thinking podcast, Daniel Kahneman, Tyler Cowen, Sam Bankman-Fried

Alfonso Escudero, $75,000, to create a platform for scientific collaborations. Alfonso and his team already made something like this for COVID research, which got 40,000 scientists to sign up, matched collaborator requests to experts willing to help, and resulted in some useful papers. Now they want to expand this model to other types of science. My father has been stalled on an important research project for years for lack of the right kind of statistician; Crowdfight (or whatever the final name turns out to be) aims to take requests like this and process them within 72 hours. I regret only being able to fund this at the minimum level, but I'm pretty sure that once they're up and running they'll be able to prove their value to richer people's satisfaction. You can also contribute by donating, by joining their community (if you want to be matched with scientists who might need your expertise) or, if you’re a professional scientist, by using their service to find a collaborator (it's free).

Inline links: something like this, some useful papers, donating, joining their community, using their service to find a collaborator

Your Book Review: Making Nature

May 20, 2022 · Original source

The world of scientific publishing is organized as a hierarchy of status, much like the hierarchy of angels in the Abrahamic religions. At the bottom are the non-peer-reviewed blog posts and Twitter threads. Slightly above are the preprint servers like arXiv, and then big peer-reviewed journals like PLOS One. Above those are all the field-specific journals, some with higher reputation than others. And at the top, near the divine presence, are the CNS journals: Cell, Nature, and Science.

For an actual hierarchy of journals based on citation data, see this paper, which puts Nature and Science at the top. Might be worth mentioning that it comes from a journal in the Nature Publishing Group family. Leaving aside Cell, a more specialized biology journal that seems to have gotten into the CNS acronym the same way Netflix got into the FAANG acronym, Nature and Science are very similar. They both publish articles in all scientific fields. They both date from the 19th century. They’re published weekly. They jointly won a fancy prize for services to humanity in 2007. And having your paper in either is one of the best things that can happen to a scientist’s career, thanks to their immense prestige. But how, exactly, did Nature and Science become so prestigious? This is the question I hoped Making Nature: The History of a Scientific Journal, a 2015 book by historian of science Melinda Baldwin, might answer. It focuses on Nature, but much of its lessons can likely be extrapolated to Science considering their similarity. I grew curious about this when I realized that most researchers treat journal prestige as a given. Everyone knows that Nature and Science matter enormously, yet few would be able to say why exactly. But this is important! Prestigious institutions, from universities to media companies to major sports competitions, have a huge impact on the world. It’s useful to understand how they came to be, beyond “being famous for being famous.” One reason this is more difficult than it sounds is that we often settle for superficial answers. Selectivity, for instance, is a common explanation: prestige simply comes from obtaining what is hard to obtain, such as a Harvard degree, an Olympic medal or a Nobel Prize. Nature is indeed highly selective, accepting less than 10% of submitted articles (and the vast majority of papers are not even deemed worthy of a submission to Nature by their authors). Yet harsh selectivity alone cannot explain prestige, or it would be trivial to launch a prestigious journal or university just by setting an artificially low acceptance rate. Another facile explanation is longevity. It’s true that prestigious institutions are often old, and indeed Nature has been around for more than 150 years since its birth in 1869. Science is only slightly younger, having been founded in 1880. But there are many older scientific journals: the oldest one, the Philosophical Transactions of the Royal Society, was created two hundred years before Nature, in 1665. Then there are more recent publications that are prestigious: Cell, for instance, was founded in 1974. The correlation between prestige and longevity is real, but imperfect. It also says nothing of causation: does longevity cause prestige, or does prestige cause longevity? What matters is not the span of time per se, but the specific events that happened — in other words, the history. Making Nature, while not specifically about prestige, gives us exactly that. We’ll first examine the origins of Nature and how it disrupted the publishing landscape of its time (Part I). Then we’ll study the factors that allowed it to build a reputation during its first century of existence (Part II). We’ll end with a focus on the 1970s, when selectivity and prestige suddenly became important to Nature and scientific publishing in general (Part III). I. On the Origins of Nature The story begins with Nature’s founder and first editor, Norman Lockyer. Lockyer had a cushy job as a civil servant in the British government, but dabbled in astronomy in his spare time. In the 19th century, dabbling in astronomy in your spare time could be an intellectually productive hobby: the line between professional and amateur science was blurrier then, and it wasn’t hard to contribute original research even without formal training. During the 1860s, Lockyer published several papers on astronomical observations, the most consequential of which might be the co-discovery and naming of the element helium, from his studies of the sun. His reputation grew among the “men of science” (as scientists called themselves then) of Victorian Britain, and he was soon elected to the Royal Society. But astronomy was an expense, not a source of income. Lockyer routinely supplemented his government job by writing nonspecialist scientific articles and books for a lay audience. Then, one day, he had an idea for a new kind of publication. It would be a weekly periodical to disseminate scientific knowledge to the broader public — but unlike the other periodicals that existed at the time, it would be written by the prominent men of science themselves. It would have a simple, evocative name: Nature. Lockyer summarized the two aims of Nature like this: FIRST, to place before the general public the grand results of Scientific Work and Scientific Discovery, and to urge the claims of Science to a more general recognition in Education and in Daily Life; And, SECONDLY, to aid Scientific men themselves, by giving early information of all advances made in any branch of Natural knowledge throughout the world, and by affording them an opportunity of discussing the various Scientific questions which arise from time to time. In other words (and getting rid of the old-fashioned capitalization of random adjectives and nouns), Nature was meant to do two things: communication from scientists to the public, and communication among scientists. It was an interesting idea. It was also a new one; until then the two aims had been separate. Recall that scientific journals have existed since 1665. During their first two hundred years, they primarily served to record the meetings of learned societies. The Philosophical Transactions of the Royal Society were originally just that: summaries of whatever “philosophical” questions were discussed at the Royal Society. Aside from journals, specialized books were common and were in fact the higher-status way to communicate science in Victorian Britain. Charles Darwin’s On the Origins of Species, published in 1859, is the most famous example. Informal correspondence between scientists was also a major, but private, channel: Darwin wrote more than 15,000 letters in his lifetime, enough to fill 30 volumes. With the exception of some books, none of the above were intended for laypeople. Educated non-scientists (professionals, clergymen, statesmen, etc.) instead got their science news from generalist or literary periodicals such as the Athenaeum magazine. The articles in those publications were not written by specialists, but by journalists and dilettantes. Lockyer’s view, shared with his close supporter Thomas Huxley — a biologist known for defending Darwinian evolution — was that they were riddled with errors and theological overtones. It would be better, they thought, if scientists did the work of communicating their research themselves. It was bold of Lockyer and Huxley to assume that scientists would be interested in doing this communication work. They weren’t. Almost immediately after Nature was founded, its contributors ignored the popularization part (“not a high-status undertaking,” Baldwin’s book says) and focused on the intra-science communication part. They did write summaries and abstracts of their own research, as Lockyer had intended, but they expected that their readers would be other men of science. Within three years, the educated laypeople who were Lockyer’s target audience were complaining that they could no longer understand the contents. Thus the first of Nature’s two aims was met mostly with failure. Fortunately, this was balanced out by unexpected success at the second aim. Scientists did actually enjoy writing for Lockyer’s magazine, in large part because it was published weekly. They found that writing a summary of their own research in Nature was an excellent way to share their results quickly and gain attention from other scientists. Books were slow; Darwin took many years to write and publish On the Origin of Species, for instance. The journals of scientific societies were slow; you had to wait for a meeting to take place and then for the meeting’s “transactions” to be published. Private correspondence was fast, but it wasn’t public. Through publication speed, as well as other factors as we’ll see below, Nature filled a niche in the ecosystem. It was the Twitter of 19th-century British science. Soon enough, this model would be copied, most notably by the journal Science in 1880. According to its first editor, Science was explicitly meant to, “in the United States, take the position which ‘Nature’ so ably occupies in England.” In just a few years, Nature had disrupted scientific publishing and established itself as a useful and unique institution of science, recognized by specialists both in the UK and abroad. First page of the first edition of Nature, 4 November 1869 II. One Hundred Years of Building a Reputation Despite its popularity, Nature didn’t become prestigious overnight. Far from it, in fact. Making Nature often reminds us that the journal spent most of its history as a low-grade publication where anything could be printed quickly, as long as it was factually correct. (This was ensured by basic checks from the editorial team; Nature articles were not consistently peer-reviewed until the 1970s.) As late as the 1960s, a researcher publishing a preliminary report in Nature was expected to follow up with a longer paper “in a more serious journal.” In other words, Nature delivered quick and cheap distribution, not luxury brand approval. This changed about fifty years ago, as we’ll see in Part III. But to understand what happened then, we first need to examine the characteristics of the journal in the roughly 100-year period from its early days until prestige took over, starting with a deeper look into publication speed. Publication Speed John Maddox, editor of Nature in the late 20th century, said that “one of Nature’s greatest early assets was the speed of the Royal Mail.” You could write to Nature, be published within a week, and read the replies to your communication within two weeks. This was state-of-the-art communication tech! Consider how many times publication speed is mentioned throughout the first half of the book (emphasis mine): What made Nature unique was, in large part, its ability to act as a venue for . . . discussions via its correspondence columns and its weekly publication schedule. (p. 8) Many British men of science found that one of the fastest ways to bring a scientific issue or idea to their fellow researchers’ attention was to send a communication to Nature. (p. 39) Unlike the literary periodicals, there was almost no delay between the submission of a piece and its appearance in the journal. (p. 63) A second reason Nature’s speed of publication would have been compelling to men of science is that getting one’s work into print quickly had become an increasingly essential part of establishing priority for a scientific finding or theory. (p. 65) Scientific weeklies [such as Nature] played a unique role in researchers’ publishing strategies at the end of the nineteenth century by offering researchers a forum where short articles could be printed quickly. (p. 105) Both the Proceedings [of the Royal Society of London] and the Philosophical Magazine had significant lag times between submission and publication . . ., which made Nature and its weekly turnaround uniquely valuable for the priority-conscious Rutherford. (p. 109) [Rutherford] sent his most interesting experimental results [to Nature] immediately, both as a way of keeping his colleagues updated on his work and as insurance against being scooped as he had in 1899. (p. 112) These quotes highlight two distinct reasons why speed was important. The first, as I hinted at earlier, was Nature’s role as the аcademic social media of its time. It was simply the best way to have discussions about scientific topics — or science itself — that could, unlike private correspondence, reach a large audience. More on this in the next section. The second reason, as shown by the mentions of physicist Ernest Rutherford, was establishing priority. Today we take for granted that being the first to publish new ideas or results is important, but in the 19th century this was less clear. To bring up Darwin as an example again, he kept his thoughts on evolution private for many years, because he wanted to make sure his argument was sound before he submitted it to the public (although he did eventually sense the urgency of publishing the theory before Alfred Russel Wallace did). But as science became professionalized, “not being scooped” became more and more crucial, and the weekly Nature was a good tool to avoid that. All this talk of speed may surprise anyone who has recently submitted a paper to Nature. In 2016, an analysis revealed that the median time for Nature to review a paper was 150 days, i.e. 5 months, up from 85 days a decade earlier. Nature itself reports, for the year 2020, a median time of 226 days between submission and acceptance. We’re a long way from “less than a week.” Why was there a decrease in publication speed? As we might expect, the reason was Nature’s growing popularity, especially among the international scientific community. At least, that’s what happened the first time there was a slowdown, in the mid-20th century. Early on, Nature was a journal for and by British scientists. But in the first half of the 20th century, science in general and Nature in particular began to involve much more collaboration between researchers across borders. It was a big deal, for instance, when a foreign government banned Nature, as Nazi Germany did in 1938; German researchers had been using it as an important source of scientific news. The ban was furthermore covered in non-British media, such as The New York Times, indicating that the journal was internationally newsworthy. Such an increase in international readership meant more letters and articles sent to the editors, and by the 1950s, there was such a backlog that submissions needed to be held for six months or more. In the 1960s, the new editor John Maddox recognized this as a problem. He began his editorship by clearing the backlog, and even printed the date of submission along with each scientific paper to show everyone how quick Nature was at reviewing articles (“often within a month,” Baldwin’s book says). Clearly, Maddox thought that restoring the speedy reputation of the journal was important. He seems to have succeeded, for a time. As late as 1989, during a controversy around cold fusion, a Wall Street Journal article said that Nature was still fast: it was able to print papers “in as little as three weeks instead of the more usual lead time of six to twelve months for other scientific publications.” Thus, despite a dip in the middle of the century due to its popularity and international reach, speedy publication was still an important characteristic of Nature in the 1970s. A second — and so far permanent — decrease occurred more recently, perhaps as a result of prestige and the competition of near-instantaneous online platforms, but that’s another story. Network Effects As of 2022, scientists argue in public on Twitter, blogs, and other online platforms, like ResearchHub. In the 19th century, Twitter and ResearchHub hadn’t been invented [citation needed]. Fortunately, Nature was there. A network effect occurs when the value of a product comes primarily from the people who use it. If there are two competing telephone systems, the most valuable one is whichever has the most users (or at least the users you want to talk to). If you create an improved Twitter clone, then all its amazing features won’t do much if you don’t somehow manage to capture Twitter’s network of several million people. Likewise, Nature became an interesting journal to read and contribute to because it gained the attention of Britain’s scientific elite as the place to discuss big science questions. This role as a forum was a constant in Nature’s history, as Making Nature shows with several detailed accounts of debates that took place within the journal’s pages. Some examples: Controversies over the age of the Earth in the 1880s.

Inline links: this paper, a fancy prize for services to humanity, https://press.uchicago.edu/ucp/books/book/chicago/M/bo20298849.html, https://substackcdn.com/image/fetch/$s_!oY23!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F99a28e6f-d976-477a-8d14-f47510a23908_200x300.jpeg, https://substackcdn.com/image/fetch/$s_!glJ9!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F873e6e2d-15a6-4b31-954b-f24fcd5e0e23_794x1024.jpeg, more than 15,000 letters, https://en.wikipedia.org/wiki/The_Athenaeum_(British_magazine), took many years, https://substackcdn.com/image/fetch/$s_!GYj8!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fa4f03221-7d79-42f6-bf6c-35d90fe3f7e5_1142x1600.jpeg, revealed, reports, ResearchHub

Lockyer had a cushy job as a civil servant in the British government, but dabbled in astronomy in his spare time. In the 19th century, dabbling in astronomy in your spare time could be an intellectually productive hobby: the line between professional and amateur science was blurrier then, and it wasn’t hard to contribute original research even without formal training. During the 1860s, Lockyer published several papers on astronomical observations, the most consequential of which might be the co-discovery and naming of the element helium, from his studies of the sun. His reputation grew among the “men of science” (as scientists called themselves then) of Victorian Britain, and he was soon elected to the Royal Society. But astronomy was an expense, not a source of income. Lockyer routinely supplemented his government job by writing nonspecialist scientific articles and books for a lay audience. Then, one day, he had an idea for a new kind of publication. It would be a weekly periodical to disseminate scientific knowledge to the broader public — but unlike the other periodicals that existed at the time, it would be written by the prominent men of science themselves. It would have a simple, evocative name: Nature. Lockyer summarized the two aims of Nature like this: FIRST, to place before the general public the grand results of Scientific Work and Scientific Discovery, and to urge the claims of Science to a more general recognition in Education and in Daily Life; And, SECONDLY, to aid Scientific men themselves, by giving early information of all advances made in any branch of Natural knowledge throughout the world, and by affording them an opportunity of discussing the various Scientific questions which arise from time to time. In other words (and getting rid of the old-fashioned capitalization of random adjectives and nouns), Nature was meant to do two things: communication from scientists to the public, and communication among scientists. It was an interesting idea. It was also a new one; until then the two aims had been separate. Recall that scientific journals have existed since 1665. During their first two hundred years, they primarily served to record the meetings of learned societies. The Philosophical Transactions of the Royal Society were originally just that: summaries of whatever “philosophical” questions were discussed at the Royal Society. Aside from journals, specialized books were common and were in fact the higher-status way to communicate science in Victorian Britain. Charles Darwin’s On the Origins of Species, published in 1859, is the most famous example. Informal correspondence between scientists was also a major, but private, channel: Darwin wrote more than 15,000 letters in his lifetime, enough to fill 30 volumes. With the exception of some books, none of the above were intended for laypeople. Educated non-scientists (professionals, clergymen, statesmen, etc.) instead got their science news from generalist or literary periodicals such as the Athenaeum magazine. The articles in those publications were not written by specialists, but by journalists and dilettantes. Lockyer’s view, shared with his close supporter Thomas Huxley — a biologist known for defending Darwinian evolution — was that they were riddled with errors and theological overtones. It would be better, they thought, if scientists did the work of communicating their research themselves. It was bold of Lockyer and Huxley to assume that scientists would be interested in doing this communication work. They weren’t. Almost immediately after Nature was founded, its contributors ignored the popularization part (“not a high-status undertaking,” Baldwin’s book says) and focused on the intra-science communication part. They did write summaries and abstracts of their own research, as Lockyer had intended, but they expected that their readers would be other men of science. Within three years, the educated laypeople who were Lockyer’s target audience were complaining that they could no longer understand the contents. Thus the first of Nature’s two aims was met mostly with failure. Fortunately, this was balanced out by unexpected success at the second aim. Scientists did actually enjoy writing for Lockyer’s magazine, in large part because it was published weekly. They found that writing a summary of their own research in Nature was an excellent way to share their results quickly and gain attention from other scientists. Books were slow; Darwin took many years to write and publish On the Origin of Species, for instance. The journals of scientific societies were slow; you had to wait for a meeting to take place and then for the meeting’s “transactions” to be published. Private correspondence was fast, but it wasn’t public. Through publication speed, as well as other factors as we’ll see below, Nature filled a niche in the ecosystem. It was the Twitter of 19th-century British science. Soon enough, this model would be copied, most notably by the journal Science in 1880. According to its first editor, Science was explicitly meant to, “in the United States, take the position which ‘Nature’ so ably occupies in England.” In just a few years, Nature had disrupted scientific publishing and established itself as a useful and unique institution of science, recognized by specialists both in the UK and abroad. First page of the first edition of Nature, 4 November 1869 II. One Hundred Years of Building a Reputation Despite its popularity, Nature didn’t become prestigious overnight. Far from it, in fact. Making Nature often reminds us that the journal spent most of its history as a low-grade publication where anything could be printed quickly, as long as it was factually correct. (This was ensured by basic checks from the editorial team; Nature articles were not consistently peer-reviewed until the 1970s.) As late as the 1960s, a researcher publishing a preliminary report in Nature was expected to follow up with a longer paper “in a more serious journal.” In other words, Nature delivered quick and cheap distribution, not luxury brand approval. This changed about fifty years ago, as we’ll see in Part III. But to understand what happened then, we first need to examine the characteristics of the journal in the roughly 100-year period from its early days until prestige took over, starting with a deeper look into publication speed. Publication Speed John Maddox, editor of Nature in the late 20th century, said that “one of Nature’s greatest early assets was the speed of the Royal Mail.” You could write to Nature, be published within a week, and read the replies to your communication within two weeks. This was state-of-the-art communication tech! Consider how many times publication speed is mentioned throughout the first half of the book (emphasis mine): What made Nature unique was, in large part, its ability to act as a venue for . . . discussions via its correspondence columns and its weekly publication schedule. (p. 8) Many British men of science found that one of the fastest ways to bring a scientific issue or idea to their fellow researchers’ attention was to send a communication to Nature. (p. 39) Unlike the literary periodicals, there was almost no delay between the submission of a piece and its appearance in the journal. (p. 63) A second reason Nature’s speed of publication would have been compelling to men of science is that getting one’s work into print quickly had become an increasingly essential part of establishing priority for a scientific finding or theory. (p. 65) Scientific weeklies [such as Nature] played a unique role in researchers’ publishing strategies at the end of the nineteenth century by offering researchers a forum where short articles could be printed quickly. (p. 105) Both the Proceedings [of the Royal Society of London] and the Philosophical Magazine had significant lag times between submission and publication . . ., which made Nature and its weekly turnaround uniquely valuable for the priority-conscious Rutherford. (p. 109) [Rutherford] sent his most interesting experimental results [to Nature] immediately, both as a way of keeping his colleagues updated on his work and as insurance against being scooped as he had in 1899. (p. 112) These quotes highlight two distinct reasons why speed was important. The first, as I hinted at earlier, was Nature’s role as the аcademic social media of its time. It was simply the best way to have discussions about scientific topics — or science itself — that could, unlike private correspondence, reach a large audience. More on this in the next section. The second reason, as shown by the mentions of physicist Ernest Rutherford, was establishing priority. Today we take for granted that being the first to publish new ideas or results is important, but in the 19th century this was less clear. To bring up Darwin as an example again, he kept his thoughts on evolution private for many years, because he wanted to make sure his argument was sound before he submitted it to the public (although he did eventually sense the urgency of publishing the theory before Alfred Russel Wallace did). But as science became professionalized, “not being scooped” became more and more crucial, and the weekly Nature was a good tool to avoid that. All this talk of speed may surprise anyone who has recently submitted a paper to Nature. In 2016, an analysis revealed that the median time for Nature to review a paper was 150 days, i.e. 5 months, up from 85 days a decade earlier. Nature itself reports, for the year 2020, a median time of 226 days between submission and acceptance. We’re a long way from “less than a week.” Why was there a decrease in publication speed? As we might expect, the reason was Nature’s growing popularity, especially among the international scientific community. At least, that’s what happened the first time there was a slowdown, in the mid-20th century. Early on, Nature was a journal for and by British scientists. But in the first half of the 20th century, science in general and Nature in particular began to involve much more collaboration between researchers across borders. It was a big deal, for instance, when a foreign government banned Nature, as Nazi Germany did in 1938; German researchers had been using it as an important source of scientific news. The ban was furthermore covered in non-British media, such as The New York Times, indicating that the journal was internationally newsworthy. Such an increase in international readership meant more letters and articles sent to the editors, and by the 1950s, there was such a backlog that submissions needed to be held for six months or more. In the 1960s, the new editor John Maddox recognized this as a problem. He began his editorship by clearing the backlog, and even printed the date of submission along with each scientific paper to show everyone how quick Nature was at reviewing articles (“often within a month,” Baldwin’s book says). Clearly, Maddox thought that restoring the speedy reputation of the journal was important. He seems to have succeeded, for a time. As late as 1989, during a controversy around cold fusion, a Wall Street Journal article said that Nature was still fast: it was able to print papers “in as little as three weeks instead of the more usual lead time of six to twelve months for other scientific publications.” Thus, despite a dip in the middle of the century due to its popularity and international reach, speedy publication was still an important characteristic of Nature in the 1970s. A second — and so far permanent — decrease occurred more recently, perhaps as a result of prestige and the competition of near-instantaneous online platforms, but that’s another story. Network Effects As of 2022, scientists argue in public on Twitter, blogs, and other online platforms, like ResearchHub. In the 19th century, Twitter and ResearchHub hadn’t been invented [citation needed]. Fortunately, Nature was there. A network effect occurs when the value of a product comes primarily from the people who use it. If there are two competing telephone systems, the most valuable one is whichever has the most users (or at least the users you want to talk to). If you create an improved Twitter clone, then all its amazing features won’t do much if you don’t somehow manage to capture Twitter’s network of several million people. Likewise, Nature became an interesting journal to read and contribute to because it gained the attention of Britain’s scientific elite as the place to discuss big science questions. This role as a forum was a constant in Nature’s history, as Making Nature shows with several detailed accounts of debates that took place within the journal’s pages. Some examples: Controversies over the age of the Earth in the 1880s.

Inline links: more than 15,000 letters, https://en.wikipedia.org/wiki/The_Athenaeum_(British_magazine), took many years, https://substackcdn.com/image/fetch/$s_!GYj8!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fa4f03221-7d79-42f6-bf6c-35d90fe3f7e5_1142x1600.jpeg, revealed, reports, ResearchHub

Your Book Review: Viral

July 30, 2022 · Original source

A lot of these technical points are over my head, so I encourage you to read the pre-prints (as well as the critiques of them) yourself. Here are some more sources to check out about these recent pre-prints and the debate around them [1, 2, 3].

Inline links: 1, 2, 3

Virus sample sequences from early COVID patients in China were originally uploaded to an online database, but later removed in an apparent attempt at obfuscation. However, evolutionary biologist Jesse Bloom came up with a clever way to recover this data.

Inline links: However, evolutionary biologist Jesse Bloom came up with a clever way to recover this data.

Posterior: Both hypotheses seem viable and a thorough, open investigation is needed. Conclusion 2: Evaluating claims from experts and institutions There was a lesson I took away from this book that I’m not exactly sure how to feel about. Reading through the history of the investigation into the pandemic’s origins, it’s notable that many of the breakthroughs were made by either complete amateurs, or by scientists in fields outside of virology working in their free time. For example, one of the main characters in this story is The Seeker, an anonymous Twitter user, later revealed to be a former science teacher in India with no formal research experience. Again and again, amateur internet researchers like The Seeker caught things that the professional virology community missed or ignored, including the origins of RaTG13 and the eight other coronavirus samples from the Mojiang mine. I don’t really know how to feel about it. On the one hand, it’s pretty cool that science is now open source in a way that lets random, curious people comb through data to make interesting discoveries. But on the other hand, what the hell is going on if some random Twitter users are consistently correcting world-renowned virology institutes on various mistakes and omissions? This is especially frustrating when the random guy on the internet turns out to be right. When people talk about “trusting the experts”, I think they mean trusting people with technical expertise over people without technical expertise. This makes sense a lot of the time. Probably almost all the time. If you need your car fixed, have a weird rash on your skin, or have a leaking pipe in your house, you consult a mechanic, a dermatologist, or a plumber because they have the technical expertise you need on those issues. You don’t ask a random guy on Twitter for help. But what if you have a question about investment banking on Wall Street, and how it should be regulated. Should you put the question to a bunch of investment bankers? After all, they do have the most technical expertise on this subject, right? They probably know more about investment banking than you or me, or a lot of the people pushing for more financial regulations. Now we’ve run into an issue: they do have technical expertise, but it’s bundled together and intertwined with a bunch of incentives that could lead to biased judgment, so we can’t take what they’re saying as some pure, objective truth. Of course, their technical expertise is still valuable, so we shouldn’t necessarily throw out everything they say either. The proper response is to listen to what they’re saying and weigh the information accordingly after considering the incentives they’re facing, and possible biases. I guess what I’m trying to say here is that scientific institutions, though probably not as bad as Wall Street, are still made up of human beings who are susceptible to all kinds of cognitive biases, including group think, confirmation bias, and the good ol’ Not Wanting To Be Wrong. So what should we do about this? Well, the easy option is to just become an insane person, like Alex Jones, and assume the experts are lying all the time about everything. This strategy has the advantage of letting us feel edgy and rebellious, but it’s not very helpful if we actually want to figure these issues out. On the other hand, if we want to seriously try to discern truth from expert claims on controversial topics, that’s a messy challenge that involves considering their technical expertise, as well as potential biases they might have, as well as our own potential biases. Conclusion 3: Some optimism about science I know this has probably been a bit of a depressing post to read, but my final conclusion is actually one of optimism about the state of science. What differentiates science from other ways of knowing is its self-correction mechanisms. It’s all about changing our minds and reevaluating our beliefs based on new evidence and clearer understanding of things. This is basically what we’ve seen in the way the scientific community has changed positions on the lab leak hypothesis. Harsh critics might refer to this as a “flip flop”, or point out that the lab leak hypothesis never should have been dismissed in the first place, but I see it as a commendable error correction. What’s even cooler is that much of this reevaluation was the result of amateurs and semi-amateurs making discoveries based on freely accessible genomic sequence data, and open source online sequence analysis tools. Plus the fact that, despite their lack of official credentials, their analysis was taken seriously (eventually), when it became evident that they were making good points. This is a credit to the scientific community. Further sources to check out Natural Origins Proponents The most comprehensive post I’ve found making the case for natural origins is Philipp Markolin’s Substack post, which attempts to apply Bayesian reasoning to the question. Definitely recommend.

Inline links: https://substackcdn.com/image/fetch/$s_!DmBD!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fc3f437a1-b9a0-4e0a-9f6b-87872bf32576_1210x1190.png, The most comprehensive post I’ve found making the case for natural origins is Philipp Markolin’s Substack post

How Trustworthy Are Supplements?

October 05, 2022 · Original source

Both used a similar technique called DNA barcoding, where scientists check samples (in this case, herbal supplements) for fragments of DNA (in this case, from the herbs the supplements supposedly came from). Both found abysmal results. Newmaster found that a third of herbal supplements tested lacked any trace of the relevant herb, instead seeming to be some other common plant like rice. Schneiderman’s study was even more damning, finding that eighty percent of herbal supplements lacked the active ingredient. These results were extensively and mostly uncritically signal-boosted by mainstream media, for example the New York Times (1, 2) and NPR (1, 2), mostly from the perspective that supplements were a giant scam and needed to be regulated by the FDA.

Inline links: 1, 2, 1, 2

Meanwhile, Dr. Steven Newmaster, lead author of the original study, has had one of his other DNA barcoding papers retracted for suspected fraud. Science magazine did an investigative report on him, claiming that:

An investigation by Science found the problems in Newmaster’s work go well beyond the three papers. They include apparent fabrication, data manipulation, and plagiarism in speeches, teaching, biographies, and scholarly writing. A review of thousands of pages of Newmaster’s published papers, conference speeches, slide decks, and training and promotional videos, along with interviews with two dozen current and former colleagues or independent scientists and 16 regulatory or research agencies, revealed a charismatic and eloquent scientist who often exaggerated, fabulized his accomplishments, and presented other researchers’ data as his own.

Open Thread 255

December 19, 2022 · Original source

We launched a new project (which received an ACX Grant) to help improve the replication crisis in psychology: Transparent Replications by Clearer Thinking! We're aiming to vastly increase the probability of studies in top journals being replicated in order to change researcher incentives. As soon as new psychology and behavior papers come out in Nature and Science (the two most prestigious general science journals), our plan is to replicate a study from nearly every one of them. Additionally, we'll be replicating randomly selected studies from PNAS, JPSP, and PSci shortly after they are released. You can check out our first three replications now!

Inline links: Transparent Replications by Clearer Thinking, first three replications

And here’s a Vox article about their work.

Inline links: a Vox article about their work

Conventional wisdom is that intelligence-related studies replicate better than other fields, and Clearer Thinking is testing that now by trying to replicate 40 intelligence-related claims. They’re looking for experimental subjects to take their online tests; click here if you want to help. They promise you a breakdown of your cognitive strengths and weaknesses at the end, but be aware they won’t tell you your IQ and will only tell you percentile values relative to the other (highly selected) people who took their tests. Also, the Science Comprehension test is much more intense than the previous few; be prepared to put in a lot of thought if you don’t skip that one. Don’t exhaust yourself so much that you refuse to take the ACX Survey in a few weeks!

Inline links: click here

Highlights From The Comments On The Lab Leak Debate

April 09, 2024 · Original source

We've been studying Ebola for over 40 years and have yet to determine the animal reservoir. It took 20 years to identify the reservoir for HIV-1's progenitor. Sometimes finding the reservoir is easy, sometimes it's hard. Typically it is easy when you have lots of cases and the virus is not very efficient at human-to-human transmission, because that necessitates lots of separate zoonotic events, which necessitates lots of infected animals. For something that spreads fast (i.e., the kind of virus likely to start a pandemic), you don't need a big reservoir, so you have a smaller target. For example, we did find the reservoir for the 2009 flu pandemic, but it took 7 years: https://elifesciences.org/articles/16777

Inline links: https://elifesciences.org/articles/16777

Before going further, I recommend reading page 8 of the supplementary text of Worobey’s paper, titled “Robustness Of Statistical Test Results To Ascertainment Bias”, or pages 14-17, “Additional Data Related To Case Ascertainment Biases”, which explain all the reasons he thinks this isn’t true. I promise you aren’t the first person to think that maybe Worobey could be contaminated by ascertainment bias. If that still doesn’t help, Worobey talks more about his strategy for avoiding ascertainment bias here. Most important, he counted only cases from December; the market connection was discovered December 30 and added to diagnostic criteria January 3. This doesn’t mean bias is impossible - some of these points are people who caught COVID on December 31, but only got diagnosed January 4 after the new diagnostic criteria were added. But most cases are pre-criteria. And Worobey looked at various subsets of pre-criteria cases and found they were all at least as market-focused as the overall set. For example, he looked at the earliest COVID records in one Wuhan hospital system: 10 of these hospitals’ 19 earliest COVID-19 cases were linked to Huanan Market (∼53%), comparable both to Jinyintan’s 66% (of 41 cases) (4) and to the WHO-China report’s 33% of 168 retrospectively identified cases within Wuhan across December 2019 (1). Regarding cases at the Wuhan Central Hospital and HPHICWM, patients with a history of exposure at Huanan Market could not have been “cherry picked” before anyone had identified the market as an epidemiologic risk factor. Hence, there was a genuine preponderance of early COVID-19 cases associated with Huanan Market. Likewise, a study conducted January 2 (so not impacted at all by the January 3 criteria) found that 27 of 41 known patients had market links. Likewise, the first five cases were all detected in the market, and it doesn’t even make sense to talk about ascertainment bias for these. What is the Weissman paper that observeralt is talking about? It argues: if the pandemic started at the market, each seemingly non-market-linked case must ultimately derive from a market-linked case. Therefore, we should expect non-market-linked cases to require more steps than market-linked cases. Therefore, they should be further away. But if we look at the map above, we see that not-market-linked cases are closer to the market than market-linked cases. So something must be wrong, and that something might be ascertainment bias. (at least this is my interpretation of Weissman’s argument, which is more mathematical; read the paper to make sure I’m getting it right). This is a weirdly spherical-cow view of an epidemic, worthy of a physicist. It’s easy to think of reasons the linked-cases-should-be-closer rule might not hold. For example, suppose that on their lunch break, market vendors go have lunch at restaurants surrounding the market. They infect people in these restaurants, who then infect their friends and family. But these people never went to the market themselves. Now there are a bunch of non-market-linked cases immediately surrounding the wet market. But also - of all markets in Wuhan, Huanan sold the most weird wildlife. Suppose someone in the boonies gets a craving for raccoon-dog one day, their local convenience store doesn’t have it, so they hop on a bus and go downtown to the city’s main wet market. Then they get infected with COVID. Now there’s a wet-market-linked case in the boonies. In other words, we should expect two modes of spread: general geographic diffusion from the epicenter, and people from far away who made specific trips. If this still doesn’t seem obvious to you, consider - usually when COVID first arrived in America or Brazil or wherever, they were able to trace it back to a specific person from Wuhan who visited the country. If I was the first person in America to get COVID, I could usually say “Oh, it must have been my business meeting with Mr. Chin from Wuhan”. At the same time, if someone from the next town over from Wuhan got COVID, they probably couldn’t trace it back to a specific Wuhanite - everyone from Wuhan is coming and going so often that my town is just full of COVID in general. So I don’t think Weissman’s paper proves anything, and I think the general pattern of blue and orange dots suggests ascertainment bias wasn’t playing a role. So why does George Gao say that there was ascertainment bias? I looked for the direct source of the Gao quote and couldn’t find it; if someone else is able to, please let me know, since I’d be interested in exactly what he thinks about this. 1.10: Connor Reed / Gwern on cats Gwern wrote: Yes, I don't understand this (paraphrased) claim by Peter: > He also told the Mail that his cat got the coronavirus too, which is impossible. 'Impossible', thus implying the man was lying? I was under the impression that, quite aside from cats having tons of coronaviruses in general (FCoV being a particularly serious threat to young cats, which also seems to be a remarkable case study of the harms of the FDA), that it was not just not 'impossible' for domestic pet cats to get the coronavirus too, it was routine for them to get COVID-19, and even other cat species in *zoos* have tested positive and this was true very early in the COVID-19 pandemic and quite well publicized and well known (eg April 2020 https://www.nationalgeographic.com/animals/article/tiger-coronavirus-covid19-positive-test-bronx-zoo ). This was a topic of interest to me at the time because I like cats and have a cat and was wondering what the implications of me being inevitably infected might be for my cat, and so I remember this quite well despite my general attempt to remain ignorant of as many COVID-19 matters as possible... And double-checking now to see if all of these reports were somehow false positives or faked, I continue to see everyone like the CDC stating that it is still totally possible and routine for cats in close contact with infected humans (you know, like a *pet* cat) to be infected with COVID-19: https://www.cdc.gov/healthypets/covid-19/pets.html Given that Peter has supposedly spent years autistically researching every last detail and this detail in particular in order to discredit that British dude, I'm experiencing sudden Gell-Man Amnesia here about the rest of his claims, as well as the supposed experts evaluating Peter's claims if they didn't flag that (I have not checked). This is in the context of Connor Reed, a British man who claimed to have gotten COVID on November 25 - which, if true, would be surprisingly (though not impossibly) early according to the zoonosis narrative. Peter argued his story didn’t hold up, and one of his points centered around his claim that his cat might have caught COVID from him and died. Unfortunately, I mis-quoted Peter. I said Peter argued it was impossible for his cat to get COVID-19 (false). His actual statement was that it’s extremely rare for a cat to die of COVID-19. Peter, Gwern, and I then proceeded to get very confused about the exact claims and timeline, which I think is because Connor said totally different things in different interviews: In an interview with Wales Online on 2/4/2020, he said that "my kitten caught the feline coronavirus and developed pneumonia and died, but I don't think I caught it from her. I think that was just coincidence.”

Inline links: here, 4, 1, a study, the Weissman paper, https://www.nationalgeographic.com/animals/article/tiger-coronavirus-covid19-positive-test-bronx-zoo, https://www.cdc.gov/healthypets/covid-19/pets.html, an interview with Wales Online

I’m not a virologist, but I question how this comparison works. Surely HKU1 got its insert on some specific day. If you take the virus the day before, and then the other virus the day after, there will be no differences except the insert, and it will look just like COVID (ie an insert without many other mutations). The fact that the COVID comparison has few mutations, and the HKU1 insert has many mutations, just shows that whatever older virus we chose to compare HKU1 to is more distant from HKU1 than BANAL-52 (or whatever) is from COVID. Or am I missing something here? [The evidence that China tried to cover up zoonosis from the start] is untrue. They clearly said from the start this is a zoonotic spillover at HSM, and at least part of the government went to immense efforts to identify the animal, close farms, etc. (and of course couldn’t find any infected animal). Only in late 2020 did they start suspecting an import from cold-chain products after having multiple outbreaks that seem related to cold-chain products. From a Vox article from March 2023: From the start, the Chinese government interfered with efforts by both Chinese and international experts to study the pandemic, including its origins. Reporting by the AP found that even as WHO officials were publicly praising China’s cooperation, behind the scenes they were complaining about lack of access and a refusal to share data. Within months of the beginning of the pandemic, the Chinese government imposed restrictions on academic research into the origins of the novel coronavirus … China’s intransigence wasn’t unusual — countries are rarely eager to confirm that they’re the source of a deadly disease — but it went beyond the norm. International investigators weren’t permitted to see the market until more than a year after the pandemic began and a WHO-affiliated team was allowed a highly choreographed and controlled visit. The resulting report that came out of the Wuhan visit, which dismissed the possibility of a lab origin, pointed the finger at some kind of zoonotic spillover while concluding that it was unlikely that the spread started at the market, which surprised many experts. It also found that it was “possible” that the virus had been introduced via contaminated frozen food products from abroad. While few experts took that possibility seriously, it fit a narrative the Chinese government had been pushing, against nearly all evidence, that the pandemic had in fact not originated in China. “China just doesn’t want to look bad,” Filippa Lentzos, a biosecurity expert at King’s College London, told Science last August. “They need to maintain an image of control and competence. And that is what goes through everything they do.” […] it seems clear that with more cooperation, scientists could have been looking at raccoon dogs a year or more ago. “The big issue right now is that this data exists and that it is not readily available to the international community,” Maria Van Kerkhove, the WHO’s Covid-19 technical lead, told reporters on Friday. “This is first and foremost absolutely critical, not to mention that it should have been made available years earlier, but that data needs to be made accessible to individuals who can access it, who can analyze it and who can discuss it with each other.” The irony is that by making it so difficult to properly investigate a zoonotic origin of Covid, the Chinese government has created a vacuum that has been filled by claims on all sides, including the much more damning accusation that the pandemic was the result of a lab error at the Wuhan Institute of Virology. For what it’s worth, my timeline of Chinese denials and coverups looks like this: December: COVID doesn't exist, it's all lies Early January: Fine, it exists, but it’s just some wet market thing that can't spread from person to person Late January: Fine, it can spread from person to person, but we’ve got it under control now. February: Fine, it’s out of control, but you would not believe how great our response was. We're basically heroes. March: COVID was a US bioweapon, or possibly came from Italy. April: Chinese people are banned from researching the origins of COVID without government permission. 2: Comments Arguing Against Lab Leak 2.1: Is the pandemic starting near WIV reverse correlation? randomstringofcharacters wrote: Isn't [the pandemic starting near the lab] a reverse correlation issue? The lab is situated there because it's an area where coronaviruses were found in the past. Many people had this question, but Wuhan Institute of Virology was founded in 1956, didn’t originally focus on coronaviruses, and isn’t in a coronavirus hot spot. Most of WIV’s coronavirus samples come from Yunnan, about a thousand miles away. COVID’s closest relatives were found in Laos, almost two thousand miles away. During the debate, both Saar and Peter calculated the odds of a natural pandemic arising in Wuhan by dividing the population of Wuhan by the total urban population of East Asia (Saar) or South China (Peter). Saar got 1.5%, Peter got 3% (he later said this could be as high as 10% because it was a central hub in the wildlife trade). This isn’t an Official Position and I don’t think anyone else shares it, but during the debate Peter pointed out a few times that there are plenty of disease-ridden bats in Hubei (the province Wuhan is in), and that it’s not impossible that a bat virus currently known only in Laos could be active in Hubei. Still, this is the minority viewpoint and most scientists just think it involved something about the wildlife trade. 3: Other Points That Came Up 3.1: Apology to Peter re: extreme odds quiet_NaN wrote: Hot take: Peter clearly failed to convince anyone. The lab leak odds, in log10 (i.e. orders of magnitude are): Peter -20.7 Saar 2.7 Eric -3.1 Will -2.5 Scott -1.2 Daniel -1.4 One of these numbers is clearly an outlier. Scott mentions it and calls it "trolling", I would argue that it is debating in bad faith. 2e-21 is a ratio which is just silly. For one thing, the gain of function at WiV pathway is not the only pathway towards a lab leak. The WIV could also have released a naturally occurring coronavirus at the wet market. At 2e-21 odds, we would probably have to consider the possibility that the WIV built a time machine and went back in time to infect the wet market. I might have screwed up here - or at least I should have emphasized the “trolling” part. Peter complained about my presentation of his extreme-odds slide, saying: This is basically accurate. During the debate, Saar gave lots of different numbers. I don’t want to say exactly what the different numbers meant, because in earlier drafts of my post, Saar said I misunderstood them. My impression were that some of his numbers were conservative, others were central, others were extreme, others were adjusted-for-out-of-model-error, others were not-adjusted, etc. In an early draft of the post, I gave higher numbers for Saar. Saar asked me to replace them with the numbers I ended up using. I decided to agree, because I wanted to represent Saar fairly with the numbers he most centrally believed, but also because these were closest to the numbers on his Rootclaim site so it wasn’t like he was making them up just to fool me. Peter didn’t argue quite as hard, and also he didn’t have anything like the Rootclaim site, so I just took his first set of numbers. Trying to piece things together, I think a reasonable summary would be: During the debate, Saar mentioned 700-million-to-one odds in favor of lab leak, not because he thought this was plausible, but just as a discussion of where the situation would end up if you didn’t adjust for human fallibility.

Inline links: a Vox article, wrote, wrote, https://twitter.com/tgof137/status/1773797640607850745

Your Book Review: How Language Began

July 19, 2024 · Original source

This is what he looks like. According to Wikipedia, the context for this picture is: “Noam Chomsky speaks about humanity's prospects for survival” Since around 1957, Chomsky has dominated linguistics. And this matters because he is kind of a contrarian with weird ideas. Is language for communicating? No, it’s mainly for thinking: (What Kind of Creatures Are We? Ch. 1, pg. 15-16) It is, indeed, virtual dogma that the function of language is communication. ... there is by now quite significant evidence that it is simply false. Doubtless language is sometimes used for communication, as is style of dress, facial expression and stance, and much else. But fundamental properties of language design indicate that a rich tradition is correct in regarding language as essentially an instrument of thought, even if we do not go as far as Humboldt in identifying the two. Should linguists care about the interaction between culture and language? No, that’s essentially stamp-collecting: (Language and Responsibility, Ch. 2, pg. 56-57) Again, a discipline is defined in terms of its object and its results. Sociology is the study of society. As to its results, it seems that there are few things one can say about that, at least at a fairly general level. One finds observations, intuitions, impressions, some valid generalizations perhaps. All very valuable, no doubt, but not at the level of explanatory principles. … Sociolinguistics is, I suppose, a discipline that seeks to apply principles of sociology to the study of language; but I suspect that it can draw little from sociology, and I wonder whether it is likely to contribute much to it. … You can also collect butterflies and make many observations. If you like butterflies, that’s fine; but such work must not be confounded with research, which is concerned to discover explanatory principles of some depth and fails if it has not done so. Did the human capacity for language evolve gradually? No, it suddenly appeared around 50,000 years ago after a freak gene mutation: (Language and Mind, third edition, pg, 183-184) An elementary fact about the language faculty is that it is a system of discrete infinity, rare in the organic world. Any such system is based on a primitive operation that takes objects already constructed, and constructs from them a new object: in the simplest case, the set containing them. Call that operation Merge. Either Merge or some equivalent is a minimal requirement. With Merge available, we instantly have an unbounded system of hierarchically structured expressions. The simplest account of the “Great Leap Forward” in the evolution of humans would be that the brain was rewired, perhaps by some slight mutation, to provide the operation Merge … There are speculations about the evolution of language that postulate a far more complex process … A more parsimonious speculation is that they did not, and that the Great Leap was effectively instantaneous, in a single individual, who was instantly endowed with intellectual capacities far superior to those of others, transmitted to offspring and coming to predominate. At best a reasonable guess, as are all speculations about such matters, but about the simplest one imaginable, and not inconsistent with anything known or plausibly surmised. It is hard to see what account of human evolution would not assume at least this much, in one or another form. I think all of these positions are kind of insane for reasons that we will discuss later. (Side note: Chomsky’s proposal is essentially the hard takeoff theory of human intelligence.) Most consequential of all, perhaps, are the ways Chomsky has influenced (i) what linguists mainly study, and (ii) how they go about studying it. Naively, since language involves many different components—including sound production and comprehension, intonation, gestures, and context, among many others—linguists might want to study all of these. While they do study all of these, Chomsky and his followers view grammar as by far the most important component of humans’ ability to understand and produce language, and accordingly make it their central focus. Roughly speaking, grammar refers to the set of language-specific rules that determine whether a sentence is well-formed. It goes beyond specifying word order (or ‘surface structure’, in Chomskyan terminology) since one needs to know more than just where words are placed in order to modify or extend a given sentence. Consider a pair of sentences Chomsky uses to illustrate this point in Aspects of the Theory of Syntax (pg. 22), his most cited work: (1a) I expected John to be examined by a specialist. (2a) I persuaded John to be examined by a specialist. The words “expected” and “persuaded” appear in the same location in each sentence, but imply different ‘latent’ grammatical structures, or ‘deep structures’. One way to show this is to observe that a particular way of rearranging the words produces a sentence with the same meaning in the first case (1a = 1b), and a different meaning in the second (2a != 2b): (1b) I expected a specialist to examine John. (2b) I persuaded a specialist to examine John. In particular, the target of persuasion is “John” in the case of (2a), and “the specialist” in the case of (2b). A full Chomskyan treatment of sentences like this would involve hierarchical tree diagrams, which permit a precise description of deep structure. You may have encountered the famous sentence: “Colorless green ideas sleep furiously.” It first appeared in Chomsky’s 1957 book Syntactic Structures, and the point is that even nonsense sentences can be grammatically well-formed, and that speakers can quickly assess the grammatical correctness of even nonsense sentences that they’ve never seen before. To Chomsky, this is one of the most important facts to be explained about language. A naive response to Chomsky’s preoccupation with grammar is: doesn’t real language involve a lot of non-grammatical stuff, like stuttering and slips of the tongue and midstream changes of mind? Of course it does, and Chomsky acknowledges this. To address this point, Chomsky has to move the goalposts in two important ways. First, he famously distinguishes competence from performance, and identifies the former as the subject of any serious theory of language: (Aspects of the Theory of Syntax, Ch. 1, pg. 4) The problem for the linguist, as well as for the child learning the language, is to determine from the data of performance the underlying system of rules that has been mastered by the speaker-hearer and that he puts to use in actual performance. Hence, in the technical sense, linguistic theory is mentalistic, since it is concerned with discovering a mental reality underlying actual behavior. Observed use of language or hypothesized dispositions to respond, habits, and so on, may provide evidence as to the nature of this mental reality, but surely cannot constitute the actual subject matter of linguistics, if this is to be a serious discipline. Moreover, he claims that grammar captures most of what we should mean when we talk about speakers’ linguistic competence: (Aspects of the Theory of Syntax, Ch. 1, pg. 24) A grammar can be regarded as a theory of a language; it is descriptively adequate to the extent that it correctly describes the intrinsic competence of the idealized native speaker. Another way Chomsky moves the goalposts is by distinguishing E-languages, like English and Spanish and Japanese, from I-languages, which only exist inside human minds. He claims that serious linguistics should be primarily interested in the latter. In a semi-technical book summarizing Chomsky’s theory of language, Cook and Newson write: (Chomsky’s Universal Grammar: An Introduction, pg. 13) E-language linguistics … aims to collect samples of language and then describe their properties. … I-language linguistics, however, is concerned with what a speaker knows about language and where this knowledge comes from; it treats language as an internal property of the human mind rather than something external … Not only should linguistics primarily be interested in studying I-languages, but to try and study E-languages at all may be a fool’s errand: (Chomsky’s Universal Grammar: An Introduction, pg. 13) Chomsky claims that the history of generative linguistics shows a shift from an E-language to an I-language approach; ‘the shift of focus from the dubious concept of E-language to the significant notion of I-language was a crucial step in early generative grammar’ (Chomsky, 1991b, pg. 10). … Indeed Chomsky is extremely dismissive of E-language approaches: ‘E-language, if it exists at all, is derivative, remote from mechanisms and of no particular empirical significance, perhaps none at all’ (Chomsky, 1991b, pg. 10).1 I Am Not A Linguist (IANAL), but this redefinition of the primary concern of linguistics seems crazy to me. Is studying a language like English as it is actually used really of no particular empirical significance? And this doesn’t seem to be a one-time hyperbole, but a representative claim. Cook and Newson continue: (Chomsky’s Universal Grammar: An Introduction, pg. 14) The opposition between these two approaches in linguistics has been long and acrimonious, neither side conceding the other’s reality. … The E-linguist despises the I-linguist for not looking at the ‘real’ facts; the I-linguist derides the E-linguist for looking at trivia. The I-language versus E-language distinction is as much a difference of research methods and of admissible evidence as it is of long-term goals. So much for what linguists ought to study. How should they study it? The previous quote gives us a clue. Especially in the era before Chomsky (BC), linguists were more interested in description. Linguists were, at least in one view, people who could be dropped anywhere in the world, and emerge with a tentative grammar of the local language six months later. (A notion like this is mentioned early in this video.) Linguists catalog the myriad of strange details about human languages, like the fact that some languages don’t appear to have words for relative directions, or “thank you”, or “yes” and “no”. After Chomsky's domination of the field (AD), there were a lot more theorists. While you could study language by going out into the field and collecting data, this was viewed as not the only, and maybe not even the most important, way to work. Diagrams of sentences proliferated. Chomsky, arguably the most influential linguist of the past hundred years, has never done fieldwork. In summary, to Chomsky and many of the linguists working in his tradition, the scientifically interesting component of language is grammar competence, and real linguistic data only indirectly reflects it. All of this matters because the dominance of Chomskyan linguistics has had downstream effects in adjacent fields like artificial intelligence (AI), evolutionary biology, and neuroscience. Chomsky has long been an opponent of the statistical learning tradition of language modeling, essentially claiming that it does not provide insight about what humans know about languages, and that engineering success probably can’t be achieved without explicitly incorporating important mathematical facts about the underlying structure of language. Chomsky’s ideas have motivated researchers to look for a “language gene” and “language areas” of the brain. Arguably, no one has yet found either—but more on that later. How Chomsky attained this stranglehold on linguistics is an interesting sociological question, but not our main concern in the present work2. The intent here is not to pooh-pooh Chomsky, either; brilliant and hard-working people are often wrong on important questions. Consider that his academic career began in the early 1950s—over 70 years ago!—when our understanding of language, anthropology, biology, neuroscience, and artificial intelligence, among many other things, was substantially more rudimentary. Where are we going with this? All of this is context for understanding the ideas of a certain bomb-throwing terrorist blight on the face of linguistics: Daniel Everett. How Language Began is a book he wrote about, well, what language is and how it began. Everett is the anti-Chomsky. II. THE MISSIONARY We all love classic boy-meets-girl stories. Here’s one: boy meets girl at a rock concert, they fall in love, the boy converts to Christianity for the girl, then the boy and girl move to the Amazon jungle to dedicate the rest of their lives to saving the souls of an isolated hunter-gatherer tribe. Daniel Everett is the boy in this story. The woman he married, Keren Graham, is the daughter of Christian missionaries and had formative experiences living in the Amazon jungle among the Sateré-Mawé people. At seventeen, Everett became a born-again Christian; at eighteen, he and Keren married; and over the next few years, they started a family and prepared to become full-fledged missionaries like Keren’s parents. First, Everett studied “Bible and Foreign Missions” at the Moody Bible Institute in Chicago. After finishing his degree in 1975, the natural next step was to train more specifically to follow in the footsteps of Keren’s parents. In 1976, he and his wife enrolled in the Summer Institute of Linguistics (SIL) to learn translation techniques and more viscerally prepare for life in the jungle: They were sent to Chiapas, Mexico, where Keren stayed in a hut in the jungle with the couple’s children—by this time, there were three—while Everett underwent grueling field training. He endured fifty-mile hikes and survived for several days deep in the jungle with only matches, water, a rope, a machete, and a flashlight. Everett apparently had a gift for language-learning. This led SIL to invite Everett and his wife to work with the Pirahã people (pronounced pee-da-HAN), whose unusual language had thwarted all previous attempts to learn it. In 1977, Everett’s family moved to Brazil, and in December they met the Pirahã for the first time. As an SIL-affiliated missionary, Everett’s explicit goals were to (i) translate the Bible into Pirahã, and (ii) convert as many Pirahã as possible to Christianity. But Everett’s first encounter with the Pirahã was cut short for political reasons: (Don’t Sleep There Are Snakes, Ch. 1, pg. 13-14) In December of 1977 the Brazilian government ordered all missionaries to leave Indian reservations. … Leaving the village under these forced circumstances made me wonder whether I’d ever be able to return. The Summer Institute of Linguistics was concerned too and wanted to find a way around the government’s prohibition against missionaries. So SIL asked me to apply to the graduate linguistics program at the State University of Campinas (UNICAMP), in the state of São Paulo, Brazil. It was hoped that UNICAMP would be able to secure government authorization for me to visit the Pirahãs for a prolonged period, in spite of the general ban against missionaries. … My work at UNICAMP paid off as SIL hoped it would. Everett became a linguist proper sort of by accident, mostly as an excuse to continue his missionary work. But he ended up developing a passion for it. In 1980, he completed Aspects of the Phonology of Pirahã, his master’s thesis. He continued on to get a PhD in linguistics, also from UNICAMP, and in 1983 finished The Pirahã Language and Theory of Syntax, his dissertation. He continued studying the Pirahã and working as an academic linguist after that. In all, Everett spent around ten years of his life living with the Pirahã, spread out over some thirty-odd years. As he notes in Don’t Sleep, There Are Snakes: (Prologue, pg. xvii-xviii) I went to the Pirahãs when I was twenty-six years old. Now I am old enough to receive senior discounts. I gave them my youth. I have contracted malaria many times. I remember several occasions on which the Pirahãs or others threatened my life. I have carried more heavy boxes, bags, and barrels on my back through the jungle than I care to remember. But my grandchildren all know the Pirahãs. My children are who they are in part because of the Pirahãs. And I can look at some of those old men (old like me) who once threatened to kill me and recognize some of the dearest friends I have ever had—men who would now risk their lives for me. Everett interviewing some Pirahã people. (source) Everett did eventually learn their language, and it’s worth taking a step back to appreciate just how hard that task was. No Pirahã spoke Portuguese, apart from some isolated phrases they used for bartering. They didn’t speak any other language at all—just Pirahã. How do you learn another group’s language when you have no languages in common? The technical term is monolingual fieldwork. But this is just a fancy label for some combination of pointing at things, listening, crude imitation, and obsessively transcribing whatever you hear. For years. It doesn’t help that the Pirahã language seems genuinely hard to learn in a few different senses. First, it is probably conventionally difficult for Westerners to learn since it is a tonal language (two tones: high and low) with a small number of phonemes (building block sounds) and a few unusual sounds3. Second, there is no written language. Third, the language has a variety of ‘channels of discourse’, or ways of talking specialized for one or another cultural context. One of these is ‘whistle speech’; Pirahãs can communicate purely in whistles. This feature appears to be extremely useful during hunting trips: (Don’t Sleep, There Are Snakes, Ch. 11, pg. 187-188) My first intense contact with whistle speech came one day when the Pirahãs had given me permission to go hunting with them. After we’d been walking for about an hour, they decided that they weren’t seeing any game because I, with my clunking canteens and machete and congenital clumsiness, was making too much noise. “You stay here and we will be back for you later.” Xaikáibaí said gently but firmly. … As I tried to make the best of my solitary confinement, I heard the men whistling to one another. They were saying, “I’ll go over there; you go that way,” and other such hunting talk. But clearly they were communicating. It was fascinating because it sounded so different from anything I had heard before. The whistle carried long and clear in the jungle. I could immediately see the importance and usefulness of this channel, which I guessed would also be much less likely to scare away game than the lower frequencies of the men’s normal voices. Fourth, important aspects of the language reflect core tenets of Pirahã culture in ways that one might not a priori expect. Everett writes extensively about the ‘immediacy of experience principle’ of Pirahã culture, which he summarizes as the idea that: (Don’t Sleep, There Are Snakes, Ch. 7, pg. 132) Declarative Pirahã utterances contain only assertions related directly to the moment of speech, either experienced by the speaker or witnessed by someone alive during the lifetime of the speaker. One way the language reflects this is that the speaker must specify how they know something by affixing an appropriate suffix to verbs: (Don’t Sleep, There Are Snakes, Ch. 12, pg. 196) Perhaps the most interesting suffixes, however (though these are not unique to Pirahã), are what linguists call evidentials, elements that represent the speaker’s evaluation of his or her knowledge of what he or she is saying. There are three of these in Pirahã: hearsay, observation, and deduction. To see what these do, let’s use an English example. If I ask you, “Did Joe go fishing?” you could answer, “Yes, at least I heard that he did,” or “Yes, I know because I saw him leave,” or “Yes, at least I suppose he did because his boat is gone.” The difference between English and Pirahã is that what English does with a sentence, Pirahã does with a verbal suffix. Everett also convincingly links this cultural principle to the lack of Pirahã number words and creation myths. On the latter topic, Everett recalls the following exchange: (Don’t Sleep, There Are Snakes, Ch. 7, pg. 134) I sat with Kóhoi once and he asked me, after hearing about my god, “What else does your god do?” And I answered, “Well, he made the stars, and he made the earth.” Then I asked, “What do the Pirahãs say?” He answered, “Well, the Pirahãs say that these things were not made.” And all of this is to say nothing of the manifold perils of the jungle: malaria, typhoid fever, dysentery, dangerous snakes, insects, morally gray river traders, and periodic downpours. If Indiana Jones braved these conditions for years, we would consider his stories rousing adventures. Everett did this while also learning one of the most unusual languages in the world. People on the bank of the Maici river. (source) By the way, he did eventually sort of achieve his goal of translating the Bible. Armed with a solid knowledge of Pirahã, he was able to translate the New Testament’s Gospel of Mark. Since the Pirahã have no written language, he provided them with a recorded version, but did not get the reaction he expected: (Don’t Sleep, There Are Snakes, Ch. 17, pg. 267-268) When we returned to the village, I recorded Mark’s gospel in my own voice for the Pirahãs to listen to. I then brought in a wind-up tape recorder to play the recording, and I taught the Pirahãs how to use it, which, surprisingly enough, some of the children did. Keren and I left the village and returned a few weeks later. The people were still listening to the gospel, with children cranking the recorder. I was initially quite excited about this, until it became clear that the only part of the book that they paid attention to was the beheading of John the Baptist. “Wow, they cut off his head. Play that again!” One reaction to hearing the gospel caught Everett even more off-guard: (Don’t Sleep, There Are Snakes, Ch. 17, pg. 269) "The women are afraid of Jesus. We do not want him." "Why not?" I asked, wondering what had triggered this declaration. "Because last night he came to our village and tried to have sex with our women. He chased them around the village, trying to stick his large penis into them." Kaaxaóoi proceeded to show me with his two hands held far apart how long Jesus's penis was—a good three feet. But the Pirahã had an even more serious objection to Jesus: (Don’t Sleep, There Are Snakes, Ch. 17, pg. 265-266) Part of the difficulty of my task began to become clear to me. I communicated more or less correctly to the Pirahãs about my Christian beliefs. The men listening to me understood that there was a man named Hisó, Jesus, and that he wanted others to do what he told them. "The Pirahã men then asked, "Hey Dan, what does Jesus look like? Is he dark like us or light like you?" I said, "Well, I have never actually seen him. He lived a long time ago. But I do have his words." "Well, Dan, how do you have his words if you have never heard him or seen him?" They then made it clear that if I had not actually seen this guy (and not in any metaphorical sense, but literally), they weren't interested in any stories I had to tell about him. Period. This is because, as I now knew, the Pirahãs believe only what they see. Sometimes they also believe in things that someone else has told them, so long as that person has personally witnessed what he or she is reporting. In the end, Everett never converted a single Pirahã. But he did even worse than converting zero people—he lost his own faith after coming to believe that the Pirahã had a good point. After keeping this to himself for many years, he revealed his loss of faith to his family, which led to a divorce and his children breaking contact with him for a number of years afterward. But Everett losing his faith in the God of Abraham was only the beginning. Most importantly for us, he also lost his faith in the God of Linguistics—Noam Chomsky. III. THE WAR In 2005, Everett’s paper “Cultural constraints on grammar and cognition in Pirahã: Another look at the design features of human language” was published in the journal Cultural Anthropology. An outsider might expect an article like this, which made a technical observation about the apparent lack of a property called ‘recursion’ in the Pirahã language, to receive an ‘oh, neat’ sort of response. Languages can be pretty different from one another, after all. Mandarin lacks plurals. Spanish sentences can omit an explicit subject. This is one of those kinds of things. But the article ignited a firestorm of controversy that follows Everett to this day. Praise for Everett and his work on recursion in Pirahã: He became a pure charlatan, although he used to be a good descriptive linguist. That is why, as far as I know, all the serious linguists who work on Brazilian languages ignore him. Noam Chomsky, MIT professor and linguist

Inline links: Wikipedia, hard takeoff, grammar, 1, this video, don’t appear to have words for relative directions, “thank you”, “yes” and “no”, long been an opponent, 2, Daniel Everett, Sateré-Mawé people, prepared, Bible and Foreign Missions, 1975, SIL, viscerally prepare, Pirahã people, https://substackcdn.com/image/fetch/$s_!42Ji!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F5c899185-e1a2-4358-ae6a-e9298f6c7cdb_1600x1002.jpeg, source, 3, number words, https://substackcdn.com/image/fetch/$s_!yx-R!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F77975f2c-ef0f-47d7-9ed9-f22bbe04f78b_1024x768.jpeg, source, Cultural constraints on grammar and cognition in Pirahã: Another look at the design features of human language

bedobi, Redditor Apparently he struck a nerve. And there is much more vitriol like this; see Pullum for the best (short) account of the beef I’ve found, along with sources for each quote except the last. On the whole affair, he writes: Calling it a controversy or debate would be an understatement; it was a campaign of vengeance and career sabotage. I’m not going to rehash all of the details, but the conduct of many in the pro-Chomsky faction is pretty shocking. Highly recommended reading. Substantial portions of the books The Kingdom of Speech and Decoding Chomsky are also dedicated to covering the beef and related issues, although I haven’t read them. What’s going on? Assuming Everett is indeed acting in good faith, why did he get this reaction? As I said in the beginning, linguists are those who believe Noam Chomsky is the rightful caliph. Central to Chomsky’s conception of language is the idea that grammar reigns supreme, and that human brains have some specialized structure for learning and processing grammar. In the writing of Chomsky and others, this hypothetical component of our biological endowment is sometimes called the narrow faculty of language (FLN); this is to distinguish it from other (e.g., sensorimotor) capabilities relevant for practical language use. A paper by Hauser, Chomsky, and Fitch titled “The Faculty of Language: What Is It, Who Has It, and How Did It Evolve?” was published in the prestigious journal Science in 2002, just a few years earlier. The abstract contains the sentence: We hypothesize that FLN only includes recursion and is the only uniquely human component of the faculty of language. Some additional context is that Chomsky had spent the past few decades simplifying his theory of language. A good account of this is provided in the first chapter of Chomsky’s Universal Grammar: An Introduction. By 2002, arguably not much was left: the core claims were that (i) grammar is supreme, (ii) all grammar is recursive and hierarchical. More elaborate aspects of previous versions of Chomsky’s theory, like the idea that each language might be identified with different parameter settings of some ‘global’ model constrained by the human brain (the core idea of the so-called ‘principles and parameters’ formulation of universal grammar), were by now viewed as helpful and interesting but not necessarily fundamental. Hence, it stands to reason that evidence suggesting not all grammar is recursive could be perceived as a significant threat to the Chomskyan research program. If not all languages had recursion, then what would be left of Chomsky’s once-formidable theoretical apparatus? Everett’s paper inspired a lively debate, with many arguing that he is lying, or misunderstands his own data, or misunderstands Chomsky, or some combination of all of those things. The most famous anti-Everett response is “Pirahã Exceptionality: A Reassessment” by Nevins, Pesetsky, and Rodrigues (NPR), which was published in the prestigious journal Language in 2009. This paper got a response from Everett, which led to an NPR response-to-the-response. To understand how contentious even the published form of this debate became, I reproduce in full the final two paragraphs of NPR’s response-response: We began this commentary with a brief remark about the publicity that has been generated on behalf of Everett's claims about Pirahã. Although reporters and other nonlinguists may be aware of some ‘big ideas’ prominent in the field, the outside world is largely unaware of one of the most fundamental achievements of modern linguistics: the three-fold discovery that (i) there is such a thing as a FACT about language; (ii) the facts of language pose PUZZLES, which can be stated clearly and precisely; and (iii) we can propose and evaluate SOLUTIONS to these puzzles, using the same intellectual skills that we bring to bear in any other domain of inquiry. This three-fold discovery is the common heritage of all subdisciplines of linguistics and all schools of thought, the thread that unites the work of all serious modern linguists of the last few centuries, and a common denominator for the field. In our opinion, to the extent that CA and related work constitute a ‘volley fired straight at the heart’ of anything, its actual target is no particular school or subdiscipline of linguistics, but rather ANY kind of linguistics that shares the common denominator of fact, puzzle, and solution. That is why we have focused so consistently on basic, common-denominator questions: whether CA’s and E09’s conclusions follow from their premises, whether contradictory published data has been properly taken into account, and whether relevant previous research has been represented and evaluated consistently and accurately. To the extent that outside eyes may be focused on the Pirahã discussion for a while longer, we would like to hope that NP&R (and the present response) have helped reinforce the message that linguistics is a field in which robustness of evidence and soundness of argumentation matter. Two observations here. First, another statement about “serious” linguistics; why does that keep popping up? Second, wow. That’s the closest you can come to cursing someone out in a prestigious journal. Polemics aside, what’s the technical content of each side’s argument? Is Pirahã recursive or not? Much of the debate appears to hinge on two things: what one means by recursion

Inline links: bedobi, Pullum, The Kingdom of Speech, Decoding Chomsky, The Faculty of Language: What Is It, Who Has It, and How Did It Evolve?, principles and parameters, Pirahã Exceptionality: A Reassessment, response from Everett, response-to-the-response

The rub is that artificial systems engineered to perform some particular task well are not black boxes; we can look inside them and tinker as we please. Studying the internal representations and computations of such networks has provided neuroscience with crucial insights in recent years, and such approaches are particularly helpful given how costly neuroscience experiments (which might involve, e.g., training animals and expensive recording equipment) can be. Lots of recent computational neuroscience follows this blueprint: build a recurrent neural network to solve a task neuroscientists study, train it somehow, then study its internal representations to generate hypotheses about what the brain might be doing.

Your Review: Of Mice, Mechanisms, and Dementia

July 11, 2025 · Original source

This critique comes not from a conspiracist on the margins of science, but from Nobel laureate Sir Peter Medawar. A brilliant experimentalist whose work on immune tolerance laid the foundation for modern organ transplantation, Sir Peter understood both the power and the limitations of scientific communication.

But the contrived omissions can also play upon even the most well-regarded scientist’s susceptibility to the seduction of story. As Christophe Bernard, Director of Research at the Institute of Systems Neuroscience (Marseilles, Fr.) recently explained,

Inline links: recently explained

Medawar’s framing is my compass when I do deep dives into major discoveries in translational neuroscience. I approach papers with a dual vision. First, what is actually presented? But second, and often more importantly, what is not shown? How was the work likely done in reality? What alternatives were tried but not reported? What assumptions guided the experimental design? What other interpretations might fit the data if the results are not as convincing or cohesive as argued?

In Defense Of The Amyloid Hypothesis

August 14, 2025 · Original source

The “amyloid hypothesis” says that Alzheimer’s is caused by accumulation of the peptide amyloid-β. It’s the leading model in academia, but a favorite target for science journalists, contrarian bloggers, and neuroscience public intellectuals, who point out problems like:

Anti-amyloid drugs (like Aduhelm) don't reverse the disease, and only slow progression a relatively small amount. Opponents call the amyloid hypothesis zombie science, propped up only by pharmaceutical companies hoping to sell off a few more anti-amyloid me-too drugs before it collapses. Meanwhile, mainstream scientists . . . continue to believe it without really offering any public defense. Scott was so surprised by the size of the gap between official and unofficial opinion that he asked if someone from the orthodox camp would speak out in its favor. I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid. I thought I’d share that understanding with current skeptics. The ATN model The most plausible variant of the amyloid hypothesis is the A → T → N model: amyloid causes tau causes neurodegeneration. 1: Amyloid The common entrypoint, typically at least 15 years before clinically detectable symptoms [1], is accumulation of amyloid-β deposits (especially Aβ42, one of several variants). Amyloid-β is a peptide produced in healthy human beings and many other animals, probably for antimicrobial purposes [2, 3]. Factors which cause overproduction of amyloid also cause Alzheimer’s. Factors that cause decreased clearance of amyloid also cause Alzheimer’s. The clearest relationship is various genes which massively increase amyloid production (while doing nothing else); these genes are Alzheimer’s risk factors, with some of the rarer and more severe ones causing extreme versions of the disease that manifest at otherwise almost-never-seen ages. One of the clearest examples is Down syndrome, which is caused by three (rather than the usual two) copies of chromosome 21. People with Down syndrome are at much higher risk of Alzheimer’s than the general population: two-thirds will have the condition by age sixty, and 15% have it by age forty. APP, the gene for the amyloid precursor protein, is on chromosome 21. This means that people with Down syndrome will have an extra copy. This extra copy has been observed to lead to higher-than-normal amyloid levels. But there are many genes on chromosome 21; do we have additional evidence that it’s the amyloid one that’s involved? Yes. Dozens of other mutations on APP cause the same sort of extremely young and severe Alzheimer’s. So do mutations on PSEN1 and 2, the genes for the enzyme that processes amyloid precursor protein into amyloid. So do mutations on several other amyloid-related genes. [6, 91 - 96] Researchers call these autosomal-dominant Alzheimer’s, meaning Alzheimer’s cases that get inherited from a single parent in a simple fashion typical of single-gene disorders. They make up about 1% of all cases, and are our strongest evidence for the causal role of amyloid in the disorder. To my knowledge, there is no serious claim that these genes could be working through any pathway other than their shared role in the amyloid system. But these autosomal-dominant cases only make up about 1% of all Alzheimer’s patients. Might they be a different disease than the usual sporadic Alzheimer’s that strikes people without strong family histories at normal ages? Probably not: the presentation and trajectory of autosomal-dominant and sporadic Alzheimer’s cases are strikingly similar. Both show an initial appearance of amyloid pathology starting in intrinsic connectivity networks in both autosomal-dominant [14] and sporadic [15–18] types, cortical tau appearing first in the medial temporal lobe and with the exact same fold in both disease types [97] (despite human tauopathies having at least seven other possible characteristic folds [36]), that tau pathology worsening and spreading outside this region only once amyloid pathology reaches sufficient severity [65], neurodegeneration progressing closely in step with the tau pathology, and the same usual approximate trajectory of cognitive symptoms due to the sequence of affected regions. So it’s as if two bank robberies occurred hours apart, in the same town, and in a highly similar and idiosyncratic manner, and we can positively identify the culprit of one on security camera footage. It’s a good bet the culprit of the other is the same. Increased amyloid production → Alzheimer’s is an especially clear and simple pathway, but any other change in amyloid can also cause the disease. For example Overproduction or reduced clearance of amyloid due to impaired slow wave sleep. Aβ production is neuronal activity-dependent, and toxins (perhaps including Aβ) are cleared from the brain during sleep via the glymphatic system. Thus Aβ can accumulate if the brain is more active and/or has less opportunity for clearance. [7, 8, 9, 10, 11]

Inline links: Aduhelm, David Schneider-Joseph

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.

Non-Book Review Contest 2025 Winners

October 17, 2025 · Original source

Mice, Mechanisms, And Dementia, by Myka Estes. Myka is a neuroscientist and immunologist who has published in Science, Nature Reviews Neuroscience, and Immunity. She currently manages a research lab focused on children with profound neurodevelopmental disorders and publishes the Journal Club with Myka Substack. She’s also in the process of launching an independent bookstore, and in her spare time - she has no spare time.

Inline links: Mice, Mechanisms, And Dementia, Journal Club with Myka

My Father’s Instant Mashed Potatoes, by Chris Finkle. Chris manages a makerspace in central Florida, and despite writing a review about the perils of simulacra he spends much of his free time at various theme parks, haunts, and roadside attractions. His most active social media presence is letterboxd, where he watches at least one movie from each of the last hundred years every year. This was his first time entering an ACX contest, and his other short form writing (mostly science fiction and reflections on pop culture) can be found at The Viewer From Nowhere.

Inline links: My Father’s Instant Mashed Potatoes, letterboxd, science fiction, reflections on pop culture, The Viewer From Nowhere

Miniatur Wunderland, reviewed by Laura González Salmerón. Laura works on the advising team at 80,000 Hours. The world is racing towards transformative AI without much of a plan: apply to speak with the team if you want to use your career to do something about it. Outside work, she’s chipping away at a PhD on representations of science in fiction. She’s using this contest as an excuse to launch a Substack she’s been meaning to start for years, The Turing Text (we’ll see how long it lasts). Blogging about literature, linguistics, and AI seems like productive thesis procrastination.

Inline links: Miniatur Wunderland, apply, The Turing Text

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Astral Codex Ten

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