4 ms·

There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientists to siphon money away from r

There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientists to siphon money away from research that works. It’s a whole thing. I anssume it’s because Alzheimer’s legitimately sucks (my mom has it) and that means there has to be someone we can blame.

smt88 1y ago
Wait, but isn't that "conspiracy" literally true? People faked data and everything... https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Amyloid&sort=byPopularity&type=story https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
alphazard 1y ago
> There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientist No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.
- KPGv2 1y ago
  > No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. The second sentence and the first sentence are merely literal and figurative descriptions of the same activity. Also, for this to be true, it has to mean lab workers knew about progress but fucked over their own family with Alzheimers. And it has to mean every single one of them did this. *Edit* Actually there's another way to interpret what you wrote. My mistake. I imagined a scenario where someone knew of progress and was dishonest by hiding it, but you might've been alluding to someone knowing an avenue wasn't fruitful but was dishonest by making it seem more fruitful. I think the latter is easier to hide than the former since it doesn't require directly fucking over your family, merely very indirectly by siphoning off a fraction of total funds to be flushed down the toilet.
  - feoren 1y ago
    The latter is what happened, for upwards of ten years. And it wasn't a small fraction of the funding -- almost no funding was allocated to any research not looking at amyloid plaques, because the intellectual giants' (falsified) research was showing that that was by far the most promising avenue to explore.
    - matthewdgreen 1y ago
      Again, there were a couple of instances of fraud in one sub-branch of a sub-branch of a field ages ago, and The Internet has decided to turn it into a conspiracy theory. On the off chance that you're actually a decent, honest person, I urge you to actually go learn about this theory that you're promoting. Go out and actually figure out the truth, because if it turns out that you're wrong about the impact and intentions, you're helping to harm a lot of people.
- feoren 1y ago
  > You can call it "evil" if you want It was a concerted and intentional effort to fake data and falsify research into a pervasive deadly disease, specifically in order to hoard funds going to research they knew was, if not a dead end, at least not nearly as promising as they were claiming, preventing those funds from going to other research groups that might actually make progress, essentially stealing donations from a charity, and using their power and clout to attack the reputations of anyone who challenged them. They directly and knowingly added some X years to how long it will take to cure this disease, with X being at least 2 and possibly as much as 10. When Alzheimer's is finally cured, add up all the people who suffered and died from it in the X years before that point, and this research team is directly and knowingly responsible for all of that suffering. Yes, I think I will call it absolutely fucking evil.
  - matthewdgreen 1y ago
    Again, I urge you to read this article and stop promoting conspiracy nonsense. I take this very personally because my mom has this disease, and people who clearly don't understand what they're talking about fuming about conspiracies really doesn't help anyone, and probably hurts them immeasurably. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
  - robwwilliams 1y ago
    Yes, I share some of your concerns about groupthink and research cliques. The best and balanced critique is Karl Herrup’s book at MIT Press: “How Not To Study a Disease”. Your comment is over the top with respect to NIH-funded researchers doing Alzheimer’s research. The emotion would be entirely appropriate if directed at RJ Reynolds Inc. and other cigarette companies or Purdue Pharma. Those are evil companies that many governments have tolerated killing for profit—Purdue Pharma and the OxyContin disaster alone about 500,000 Americans over 20 years; and US tobacco companies contribute to about as many excess deaths per year. The systematic image manipulation by a postdoctoral fellow, Dr. Sylvain Lesné, was egregious and worthy of jail time but he was a truly exceptional case and polluted 20 or more papers that did distract the entire field. You can read all about it here. PMID: 35862524 Piller C. Blots on a field? Science. 2022 377:358-363. doi: 10.1126/science.add9993
- andrewmcwatters 1y ago
  If that's not evil to you, everything wrong in your world must just be misaligned incentives.
- matthewdgreen 1y ago
  I really urge you to read this article. It was posted elsewhere in the thread as well: https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
  - alphazard 1y ago
    I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article. There is a testable prediction in your article. Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process?
    - DavidSJ 1y ago
      Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process? The author of that blog post, for whom I am in an excellent position to speak, would point to the "sole intended mechanism" clause in the testable prediction. That is, if the therapeutic's developers do not claim any other intended pathway for clinical benefit from improved BBB integrity other than amyloid−β clearance, then it would count. If not, then it would not count, even if it's plausible or even likely that that's the main pathway by which the benefits are accruing. However, because this is early preclinical research, it's not likely to reach a late-stage clinical trial within the 12-year window of the author's prediction. Furthermore, in every year there are about a dozen of these preclinical studies that go viral for some reason or other, often having little correlation with how promising the science is. I haven't had a chance to look into this one in detail, so this isn't a negative comment about it, but the base rate of this stuff panning out is low, even if it's good research. The author of that article would also point out that the concept of "the root cause" isn't terribly well-defined, but that strong evidence points to amyloid pathology as the common entrypoint in all cases of Alzheimer's disease, even if multiple upstream factors (some possibly relating to the BBB) can feed into that, depending on the specific case. Similarly, calorie surplus causes obesity in nearly all cases, but the specific cause of calorie surplus may vary from person to person. I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article. A correction: the article does discuss other hypotheses, in pointing out that they can't account for crucial evidence, whereas there isn't any major evidence the amyloid hypothesis seems to have trouble accounting for, and it thus remains very strong.
mrguyorama 1y ago
It's a whole thing because there's been over a century of concerted effort in the US to cast all of science as an evil plot. The Discovery institute, and all their donors and connections (including literal politicians) tell millions of children that science is a plot of satan to make you doubt god. The people who created the Scopes "monkey trial" never went away, are fabulously well funded and organized and connected, and have succeeded beyond their wildest dreams Now they are trying to expand that belief to all of academia, so that people who never set foot in an academic institution and have never tried any higher education beyond high school and have never even attempted to read a scientific paper are convinced that all Academics are in a concerted plot. 30 million Americans claim to believe God created humans exactly as they are now within the past 10k years. That's the low estimate of christian fundamentalism and science hostile cohort in the US.
- ashtakeaway 1y ago
  The science hostile cohort is flourishing wherever christian fundamentalism is rampant, in some places most people are exactly this. A lot of the depressing things Carl Sagan mentioned in Demon Haunted World turns out to be true. I had thought that 20 years ago we were on our way to being a rational society but it turned out this notion was on its way out.
  - neves 1y ago
    The USA was founded by fundamentalists. They where expelled from England. They were ridiculed and called Puritans. USA also was the only occidental country to forbid alcohol consumption, like Saudi Arabia today. The irrational genes are in the fabric of American society.
    - larsiusprime 1y ago
      Cmon the puritans were one of many different founding cohorts. Quakers, borderers, cavaliers, etc. America was never of one mind on the subject of religion.
- regnull 1y ago
SZJX 1y ago
Not sure it’s a “long-running Internet movement”. You make it sound like one of those loony anti-science conspiracist agendas. There have been a lot of serious articles written about it. I don’t think it’s hard to believe that a lot of scientists and institutions have the incentive to try to keep a whole system of focusing on removing beta-amyloid going as a self-fulfilling cycle. Getting funding and publication citations snd promotions etc. could always be the fundamental incentive out there.
- fithisux 1y ago
  Sabine Hossenfelder uncovered a whole industry in theoretical physics.
  - pas 1y ago
    did she? or is she simply preaching to a certain choir that's awash with the heavy anti-establishment and anti-intellectual sentiment of nowadays? https://www.youtube.com/watch?v=miJbW3i9qQc https://www.youtube.com/watch?v=miJbW3i9qQc https://www.youtube.com/watch?v=70vYj1KPyT4 https://www.youtube.com/watch?v=70vYj1KPyT4 ... that said, of course there's some valid criticism of science funding underneath, and (the whole role, purpose, and status of) the academic sphere (with its traditions and privileges) which largely determines the outcome of how grant organizations end doing funding decisions.
    - fithisux 1y ago
      I've been doing research as a post-graduate and I can definitely say that a big part of academia is just an echo chamber for what is mainstream. Mainstream is not necessarily bad. But the echo chamber happens uncritically and even in bad research. It is frightening at least.
- pas 1y ago
  the problem is that ... there's currently no better theory that matches the data than the amyloid cascade one - as far as I understand (and of course I'm extremely far from an expert on this) still, I think it's correct to state that it's very hard to falsify the hypothesis, because it says that AD (Alzheimer's disease) goes through the following stages: unknown proximate cause leads to appearance of amyloid plaques which then irreversibility lead to Tau bundles (tangles) which inevitably lead to neurodegeneration which then show up as AD the model states that by the time the plaques are there it's "too late" of course there are drugs being tested to try to "solve" this from multiple angles, for example make the progression slow enough to "not matter", prevent the tau bundles, etc. ... https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h... see also "In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more": https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1459224/full https://www.frontiersin.org/journals/aging-neuroscience/arti... in particular I recommend looking at this diagram that shows how the model has evolved over the decades: https://www.frontiersin.org/files/Articles/1459224/fnagi-16-1459224-HTML/image_m/fnagi-16-1459224-g001.jpg https://www.frontiersin.org/files/Articles/1459224/fnagi-16-...

smt88 1y ago

Wait, but isn't that "conspiracy" literally true? People faked data and everything... https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Amyloid&sort=byPopularity&type=story https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...

alphazard 1y ago

> There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientist No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.

KPGv2 1y ago
> No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. The second sentence and the first sentence are merely literal and figurative descriptions of the same activity. Also, for this to be true, it has to mean lab workers knew about progress but fucked over their own family with Alzheimers. And it has to mean every single one of them did this. *Edit* Actually there's another way to interpret what you wrote. My mistake. I imagined a scenario where someone knew of progress and was dishonest by hiding it, but you might've been alluding to someone knowing an avenue wasn't fruitful but was dishonest by making it seem more fruitful. I think the latter is easier to hide than the former since it doesn't require directly fucking over your family, merely very indirectly by siphoning off a fraction of total funds to be flushed down the toilet.
- feoren 1y ago
  The latter is what happened, for upwards of ten years. And it wasn't a small fraction of the funding -- almost no funding was allocated to any research not looking at amyloid plaques, because the intellectual giants' (falsified) research was showing that that was by far the most promising avenue to explore.
  - matthewdgreen 1y ago
    Again, there were a couple of instances of fraud in one sub-branch of a sub-branch of a field ages ago, and The Internet has decided to turn it into a conspiracy theory. On the off chance that you're actually a decent, honest person, I urge you to actually go learn about this theory that you're promoting. Go out and actually figure out the truth, because if it turns out that you're wrong about the impact and intentions, you're helping to harm a lot of people.
feoren 1y ago
> You can call it "evil" if you want It was a concerted and intentional effort to fake data and falsify research into a pervasive deadly disease, specifically in order to hoard funds going to research they knew was, if not a dead end, at least not nearly as promising as they were claiming, preventing those funds from going to other research groups that might actually make progress, essentially stealing donations from a charity, and using their power and clout to attack the reputations of anyone who challenged them. They directly and knowingly added some X years to how long it will take to cure this disease, with X being at least 2 and possibly as much as 10. When Alzheimer's is finally cured, add up all the people who suffered and died from it in the X years before that point, and this research team is directly and knowingly responsible for all of that suffering. Yes, I think I will call it absolutely fucking evil.
- matthewdgreen 1y ago
  Again, I urge you to read this article and stop promoting conspiracy nonsense. I take this very personally because my mom has this disease, and people who clearly don't understand what they're talking about fuming about conspiracies really doesn't help anyone, and probably hurts them immeasurably. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
- robwwilliams 1y ago
  Yes, I share some of your concerns about groupthink and research cliques. The best and balanced critique is Karl Herrup’s book at MIT Press: “How Not To Study a Disease”. Your comment is over the top with respect to NIH-funded researchers doing Alzheimer’s research. The emotion would be entirely appropriate if directed at RJ Reynolds Inc. and other cigarette companies or Purdue Pharma. Those are evil companies that many governments have tolerated killing for profit—Purdue Pharma and the OxyContin disaster alone about 500,000 Americans over 20 years; and US tobacco companies contribute to about as many excess deaths per year. The systematic image manipulation by a postdoctoral fellow, Dr. Sylvain Lesné, was egregious and worthy of jail time but he was a truly exceptional case and polluted 20 or more papers that did distract the entire field. You can read all about it here. PMID: 35862524 Piller C. Blots on a field? Science. 2022 377:358-363. doi: 10.1126/science.add9993
andrewmcwatters 1y ago
If that's not evil to you, everything wrong in your world must just be misaligned incentives.
matthewdgreen 1y ago
I really urge you to read this article. It was posted elsewhere in the thread as well: https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
- alphazard 1y ago
  I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article. There is a testable prediction in your article. Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process?
  - DavidSJ 1y ago
    Unfortunately, I don't think the mechanism is quite restricted enough. TFA says that repairing the BBB helps amyloid plaque clearance. Would the author of your blog post claim that as a win, or admit that the plaques are downstream of the problem, and that BBB integrity is closer to the root cause of the disease process? The author of that blog post, for whom I am in an excellent position to speak, would point to the "sole intended mechanism" clause in the testable prediction. That is, if the therapeutic's developers do not claim any other intended pathway for clinical benefit from improved BBB integrity other than amyloid−β clearance, then it would count. If not, then it would not count, even if it's plausible or even likely that that's the main pathway by which the benefits are accruing. However, because this is early preclinical research, it's not likely to reach a late-stage clinical trial within the 12-year window of the author's prediction. Furthermore, in every year there are about a dozen of these preclinical studies that go viral for some reason or other, often having little correlation with how promising the science is. I haven't had a chance to look into this one in detail, so this isn't a negative comment about it, but the base rate of this stuff panning out is low, even if it's good research. The author of that article would also point out that the concept of "the root cause" isn't terribly well-defined, but that strong evidence points to amyloid pathology as the common entrypoint in all cases of Alzheimer's disease, even if multiple upstream factors (some possibly relating to the BBB) can feed into that, depending on the specific case. Similarly, calorie surplus causes obesity in nearly all cases, but the specific cause of calorie surplus may vary from person to person. I can't guess what point you're trying to make with a long article that acknowledges the fraud in the beginning, and then rehashes the initial reasons for looking into the amyloid hypothesis. No one is claiming it was stupid to look into the amyloid hypothesis. They are complaining that it hasn't been the most promising theory in quite a long time, and it was fraudulently held as the most promising. Other theories, arguably more promising, are listed throughout your article. A correction: the article does discuss other hypotheses, in pointing out that they can't account for crucial evidence, whereas there isn't any major evidence the amyloid hypothesis seems to have trouble accounting for, and it thus remains very strong.

mrguyorama 1y ago

It's a whole thing because there's been over a century of concerted effort in the US to cast all of science as an evil plot. The Discovery institute, and all their donors and connections (including literal politicians) tell millions of children that science is a plot of satan to make you doubt god. The people who created the Scopes "monkey trial" never went away, are fabulously well funded and organized and connected, and have succeeded beyond their wildest dreams Now they are trying to expand that belief to all of academia, so that people who never set foot in an academic institution and have never tried any higher education beyond high school and have never even attempted to read a scientific paper are convinced that all Academics are in a concerted plot. 30 million Americans claim to believe God created humans exactly as they are now within the past 10k years. That's the low estimate of christian fundamentalism and science hostile cohort in the US.

ashtakeaway 1y ago
The science hostile cohort is flourishing wherever christian fundamentalism is rampant, in some places most people are exactly this. A lot of the depressing things Carl Sagan mentioned in Demon Haunted World turns out to be true. I had thought that 20 years ago we were on our way to being a rational society but it turned out this notion was on its way out.
- neves 1y ago
  The USA was founded by fundamentalists. They where expelled from England. They were ridiculed and called Puritans. USA also was the only occidental country to forbid alcohol consumption, like Saudi Arabia today. The irrational genes are in the fabric of American society.
  - larsiusprime 1y ago
    Cmon the puritans were one of many different founding cohorts. Quakers, borderers, cavaliers, etc. America was never of one mind on the subject of religion.
regnull 1y ago

SZJX 1y ago

Not sure it’s a “long-running Internet movement”. You make it sound like one of those loony anti-science conspiracist agendas. There have been a lot of serious articles written about it. I don’t think it’s hard to believe that a lot of scientists and institutions have the incentive to try to keep a whole system of focusing on removing beta-amyloid going as a self-fulfilling cycle. Getting funding and publication citations snd promotions etc. could always be the fundamental incentive out there.

fithisux 1y ago
Sabine Hossenfelder uncovered a whole industry in theoretical physics.
- pas 1y ago
  did she? or is she simply preaching to a certain choir that's awash with the heavy anti-establishment and anti-intellectual sentiment of nowadays? https://www.youtube.com/watch?v=miJbW3i9qQc https://www.youtube.com/watch?v=miJbW3i9qQc https://www.youtube.com/watch?v=70vYj1KPyT4 https://www.youtube.com/watch?v=70vYj1KPyT4 ... that said, of course there's some valid criticism of science funding underneath, and (the whole role, purpose, and status of) the academic sphere (with its traditions and privileges) which largely determines the outcome of how grant organizations end doing funding decisions.
  - fithisux 1y ago
    I've been doing research as a post-graduate and I can definitely say that a big part of academia is just an echo chamber for what is mainstream. Mainstream is not necessarily bad. But the echo chamber happens uncritically and even in bad research. It is frightening at least.
pas 1y ago
the problem is that ... there's currently no better theory that matches the data than the amyloid cascade one - as far as I understand (and of course I'm extremely far from an expert on this) still, I think it's correct to state that it's very hard to falsify the hypothesis, because it says that AD (Alzheimer's disease) goes through the following stages: unknown proximate cause leads to appearance of amyloid plaques which then irreversibility lead to Tau bundles (tangles) which inevitably lead to neurodegeneration which then show up as AD the model states that by the time the plaques are there it's "too late" of course there are drugs being tested to try to "solve" this from multiple angles, for example make the progression slow enough to "not matter", prevent the tau bundles, etc. ... https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h... see also "In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more": https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1459224/full https://www.frontiersin.org/journals/aging-neuroscience/arti... in particular I recommend looking at this diagram that shows how the model has evolved over the decades: https://www.frontiersin.org/files/Articles/1459224/fnagi-16-1459224-HTML/image_m/fnagi-16-1459224-g001.jpg https://www.frontiersin.org/files/Articles/1459224/fnagi-16-...