5 ms·

I recommend reading the comments on AlzForum [1]. From the discussions, it sounds like this fraud is significant in terms of Dr. Sylvain Lesné's work, but that

I recommend reading the comments on AlzForum [1]. From the discussions, it sounds like this fraud is significant in terms of Dr. Sylvain Lesné's work, but that the news has been vastly blown out of proportion. These comments are written by real Alzheimer's researchers. They all disagree with the notion that Lesné's papers have been important to the field, and therefore undermine the idea that this has any bearing on "two decades of Alzheimer's research". (Karen Ashe, co-author of the main paper referenced here, also stops by the thread.) [1] https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-accused-image-manipulation https://www.alzforum.org/news/community-news/sylvain-lesne-w...

plutonorm 4y ago
And how many of those commenters have a vested interest in the current research direction?
- mwt 4y ago
  It's pretty disrespectful to signal (without evidence or elaboration) that researchers are not credible (or worse, broadly lying) in order to keep their research grants flowing. A hypothesis that turns out to be wrong is something both industry and government are obviously not going to invest further in. The people working in the field have skills to transfer to other departments and projects; these aren't the sort of scientists and engineers that are out of ideas or work to do. It's also plenty obvious that there is no single, monolithic "current research direction" or even that this researcher's work was of fundamental impact when it was published - not to mention the number of people that were highly skeptical from the beginning.
  - nostrebored 4y ago
    Given everything we know about how research funding has been captured and shaky ethics in particular domains, skepticism is warranted, not disrespectful.
    - User23 4y ago
      Also, “believe science” is the exact opposite of the scientific method.
      - sonotathrowaway 4y ago
        “Hurl unfounded and baseless accusations of personal corruption” is not the scientific method either. Trying to pass off conspiracy theorist “disprove the negative” arguments as reasonable discourse is intellectually lazy, at best.
        User23 4y ago
        Is that an accusation of bad faith or just a non sequitur?
      - stjohnswarts 4y ago
        There is that minor issue that we don't have nearly the same experience and resources as the scientists who say what they say. Are you implying we all becom biologists and figure out the source of Alzheimer's ourselves? As some point you have to trust people and choose someone.
    - mwt 4y ago
      I'm not asking for people to turn off skepticism or blindly trust researchers. It's not disrespectful to be skeptical. What is disrespectful is not bothering to read what people have to say before dismissing them as liars who are too vested in "the current research direction" and/or money for their perspectives to matter. It only takes reading a few comments to see that's not happening - for starters, people were skeptical of this group's work for a while now.
  - BurningFrog 4y ago
    - tptacek 4y ago
      My feeling is that the only reason HN doesn't have a guideline rule forbidding cites to "Upton's Law" is that there isn't space for it. It's tired, snarky, provides no insight, and never takes the conversation in any interesting direction. The comment you're replying to observes that a bunch of researchers say that the fraudulent paper simply isn't that important in the field. You can contest that claim! Maybe they're totally wrong! But you can't do so with Upton Sinclair, because Upton knows nothing at all about how Alzheimers research works, and when you deploy that quote, you give the strong impression that you don't either.
      - pvg 4y ago
        there isn't space for it First they came for Upton's Law... Could be squeezed in maybe: Eschew flamebait. Avoid unrelated controversies, generic tangents and internet tropes https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=author%3Adang%20%22internet%20trope%22&sort=byDate&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
        tptacek 4y ago
        If at first they don't come for Upton's Law, then you're the product.
        dang 4y ago
        That is, as Bill Clinton said to Christopher Buckley, goddamn funny.
        dang 4y ago
        Hey that's a good idea. Thanks! I'll add it, along with an Oxford comma. Edit: done. But perhaps we should take out "internet" and just say "tropes"?
  - deleted 4y ago
    [deleted]
  - patrick451 4y ago
    It's not disrespectful to point out conflicts of interest. Recusing yourself is standard practice for good reason.
    - mwt 4y ago
      Harboring skepticism of the work people did with a seemingly fraudulent researcher is a good idea. Dismissing everybody in a field whether or not their work is fraudulent is disrespectful approach (not to mention useless).
      - sonotathrowaway 4y ago
        It’s not even a good faith argument, people cannot prove they’re not biased. It’s just your basic lazy conspiracy theory thinking dressed up as cynical aloofness.
  - plutonorm 4y ago
    lol
  - lamontcg 4y ago
    Based on the way that string theory keeps on going like a zombie in physics, I don't think its disrespectful at all to consider allegations that are pretty much indistinguishable from those. Although I think that heavily entrenched groupthink and biases are all that is required. I don't think they're consciously think that "I need to lie in order to keep the research grants flowing" but its instead that old adage that "It is difficult to get a man to understand something, when his salary depends on his not understanding it". To an external observer those are largely indistinguishable and have the same effect, but in the latter case the person has convinced themselves of the lie or the half-truth via financially inclined self-deception.
    - mwt 4y ago
      I think there is truth to the general principle you refer to, but I don't think it accurately describes what I saw skimming experts' comments in the linked thread. I'm an outsider to medical research but have experience in other parts of STEM research at universities. Here I saw a plenty of nuance, documentation of historical skepticism, concern over broad perception, and plenty disagreement over technical points. Far from a unified kool-aid drinker sort of situation. And I think there has been plenty of changes of opinions in the Alzheimer's field in recent years given the number of failed drugs - which goes against the idea that these scientists are following their career over the evidence.
      - lamontcg 4y ago
        But people who are motivated by a decade or two of having their salaries paid by the leading hypothesis aren't going to produce unified kool-aid drinker kinds of rationales to support it. They've had decades to internalize the arguments and they will be nuanced and multifaceted. They're experts and their defense of the old paradigm will look just like expert opinion. There can still be rotten core foundations at the bottom of it all.
        mwt 4y ago
        I'm not claiming there are no overly stubborn PIs. But we should not be lazy and paint so a brush that we view the field as a monolith.
- kasabali 4y ago
  See related : "Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019)" https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 (also see dang's comment who lists 2 more thread https://news.ycombinator.com/item?id=32213973 https://news.ycombinator.com/item?id=32213973) Parent comment is downvoted but it seems like most alzheimer's researchers have vested interest in amyloid hypothesis one way or the other.
ncmncm 4y ago
- civilized 4y ago
  Jumping to conclusions again? Beware of confident cynicism as a substitute for technical expertise.
  - orlp 4y ago
    It's absolutely jumping to conclusions, but so is blindly believing the people saying that the impact of it is low, when those very people are the authors which would be impacted. I'd say we'll have to wait and see.
    - civilized 4y ago
      I agree. It's a technical question at this point, and with all the attention now on it, there seem to be favorable conditions for a thorough investigation.
      - ncmncm 4y ago
        That is not what I got from the comments there. What I got was "damn the torpedoes, full speed ahead on amyloids!" When it is finally proven that interfering with amyloid synthesis never has any desirable effect of any kind, what will these people do instead of fooling with them?
        civilized 4y ago
        This is a bit against Hacker News rules so I'm going to say this once and only once. You run around commenting on many diverse fields that no single human could possibly be an expert on simultaneously. These comments come with a consistent attitude: your position is obviously right, and only evil or self-interested establishments stand in the way of that being acknowledged. There are many other human beings who are just as smart as you or smarter, and just as invested in truth and goodness. Is it likely that you have the royal road to these things?
civilized 4y ago
I agree, the discussion here is reassuring. This may just be a case of a fraudulent paper piggybacking on an otherwise credible research program focusing on amyloid oligomers - not the plaques which recent failed therapies have targeted, and which many of these researchers knew were poor targets for decades before the FDA debacle over aducanumab. We can blame regulatory capture of the FDA for approval of failed drugs, rather than the scientific establishment. And we can blame Sylvain Lesné for Sylvain Lesné's fraud. I would encourage those of us whose only knowledge of this topic is the word "amyloid" (I admit I am one of them) to read the scientists' comments and appreciate that there is more to this than we know. There are complexities, nuances, diverse perspectives and healthy disagreements. It's not just a political battlefield. Projecting culture war into it would be harmful to the scientific progress we all value and to the millions who suffer from Alzheimer's.
- koheripbal 4y ago
  Their comments are not without self-interest. They all see the potential of their own funding being re-evaluated if they admit that any of their ongoing research build's on (or even references) Sylvain Lesné's work. They have an interest in limiting the scope of the perception of fraud in the field.
  - civilized 4y ago
    And the people who want a change in direction have an interest in calling out any of that sort of thing that may be happening. So if it is, I hope to see it called out in a scientifically substantial way.
kasabali 4y ago
I recommend reading these instead: Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=31828509 How an Alzheimer’s ‘cabal’ thwarted progress toward a cure https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 The amyloid hypothesis on trial https://news.ycombinator.com/item?id=17618027 https://news.ycombinator.com/item?id=17618027 Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) https://news.ycombinator.com/item?id=17444214 https://news.ycombinator.com/item?id=17444214 Why, at this point should we believe any one scientist writing in that forum wasn't already sunk far deep into amyloid research in their career? Not to mention that after a quick glance on the comments section, I fail to see where you get the idea that "They all disagree with the notion that Lesné's papers have been important to the field". Apart from the very first comment from karen Ashe (who will obviously be defending her research) and a few other who's working on related topics, other commenters seems to be keeping their suspicion at amyloid hypothesis.
- user1337331 4y ago
  Rather than just scrutinizing a single hypothesis for AD we must understand that it is a multi factorial disease and that there are other hypotheses as well (i.e., acetylcholine, tau, transport-clearance), which affect and complicate this disease. Furthermore, we know very little about the brain, hence why novel therapies consistently fail in the clinic compared to other diseases (i.e., cancer). Most of these antibodies that target amyloid don’t even cross the blood-brain barrier (<0.1% and need an effective dose of 1000x blood-plasma for effective amyloid lowering) - provided with this, can we really attest the failure of the amyloid hypothesis? Moreover, the commenters there are big names in the AD community

plutonorm 4y ago

And how many of those commenters have a vested interest in the current research direction?

mwt 4y ago
It's pretty disrespectful to signal (without evidence or elaboration) that researchers are not credible (or worse, broadly lying) in order to keep their research grants flowing. A hypothesis that turns out to be wrong is something both industry and government are obviously not going to invest further in. The people working in the field have skills to transfer to other departments and projects; these aren't the sort of scientists and engineers that are out of ideas or work to do. It's also plenty obvious that there is no single, monolithic "current research direction" or even that this researcher's work was of fundamental impact when it was published - not to mention the number of people that were highly skeptical from the beginning.
- nostrebored 4y ago
  Given everything we know about how research funding has been captured and shaky ethics in particular domains, skepticism is warranted, not disrespectful.
  - User23 4y ago
    Also, “believe science” is the exact opposite of the scientific method.
    - sonotathrowaway 4y ago
      “Hurl unfounded and baseless accusations of personal corruption” is not the scientific method either. Trying to pass off conspiracy theorist “disprove the negative” arguments as reasonable discourse is intellectually lazy, at best.
      - User23 4y ago
        Is that an accusation of bad faith or just a non sequitur?
    - stjohnswarts 4y ago
      There is that minor issue that we don't have nearly the same experience and resources as the scientists who say what they say. Are you implying we all becom biologists and figure out the source of Alzheimer's ourselves? As some point you have to trust people and choose someone.
  - mwt 4y ago
    I'm not asking for people to turn off skepticism or blindly trust researchers. It's not disrespectful to be skeptical. What is disrespectful is not bothering to read what people have to say before dismissing them as liars who are too vested in "the current research direction" and/or money for their perspectives to matter. It only takes reading a few comments to see that's not happening - for starters, people were skeptical of this group's work for a while now.
- BurningFrog 4y ago
  - tptacek 4y ago
    My feeling is that the only reason HN doesn't have a guideline rule forbidding cites to "Upton's Law" is that there isn't space for it. It's tired, snarky, provides no insight, and never takes the conversation in any interesting direction. The comment you're replying to observes that a bunch of researchers say that the fraudulent paper simply isn't that important in the field. You can contest that claim! Maybe they're totally wrong! But you can't do so with Upton Sinclair, because Upton knows nothing at all about how Alzheimers research works, and when you deploy that quote, you give the strong impression that you don't either.
    - pvg 4y ago
      there isn't space for it First they came for Upton's Law... Could be squeezed in maybe: Eschew flamebait. Avoid unrelated controversies, generic tangents and internet tropes https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=author%3Adang%20%22internet%20trope%22&sort=byDate&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
      - tptacek 4y ago
        If at first they don't come for Upton's Law, then you're the product.
        dang 4y ago
        That is, as Bill Clinton said to Christopher Buckley, goddamn funny.
      - dang 4y ago
        Hey that's a good idea. Thanks! I'll add it, along with an Oxford comma. Edit: done. But perhaps we should take out "internet" and just say "tropes"?
- deleted 4y ago
  [deleted]
- patrick451 4y ago
  It's not disrespectful to point out conflicts of interest. Recusing yourself is standard practice for good reason.
  - mwt 4y ago
    Harboring skepticism of the work people did with a seemingly fraudulent researcher is a good idea. Dismissing everybody in a field whether or not their work is fraudulent is disrespectful approach (not to mention useless).
    - sonotathrowaway 4y ago
      It’s not even a good faith argument, people cannot prove they’re not biased. It’s just your basic lazy conspiracy theory thinking dressed up as cynical aloofness.
- plutonorm 4y ago
  lol
- lamontcg 4y ago
  Based on the way that string theory keeps on going like a zombie in physics, I don't think its disrespectful at all to consider allegations that are pretty much indistinguishable from those. Although I think that heavily entrenched groupthink and biases are all that is required. I don't think they're consciously think that "I need to lie in order to keep the research grants flowing" but its instead that old adage that "It is difficult to get a man to understand something, when his salary depends on his not understanding it". To an external observer those are largely indistinguishable and have the same effect, but in the latter case the person has convinced themselves of the lie or the half-truth via financially inclined self-deception.
  - mwt 4y ago
    I think there is truth to the general principle you refer to, but I don't think it accurately describes what I saw skimming experts' comments in the linked thread. I'm an outsider to medical research but have experience in other parts of STEM research at universities. Here I saw a plenty of nuance, documentation of historical skepticism, concern over broad perception, and plenty disagreement over technical points. Far from a unified kool-aid drinker sort of situation. And I think there has been plenty of changes of opinions in the Alzheimer's field in recent years given the number of failed drugs - which goes against the idea that these scientists are following their career over the evidence.
    - lamontcg 4y ago
      But people who are motivated by a decade or two of having their salaries paid by the leading hypothesis aren't going to produce unified kool-aid drinker kinds of rationales to support it. They've had decades to internalize the arguments and they will be nuanced and multifaceted. They're experts and their defense of the old paradigm will look just like expert opinion. There can still be rotten core foundations at the bottom of it all.
      - mwt 4y ago
        I'm not claiming there are no overly stubborn PIs. But we should not be lazy and paint so a brush that we view the field as a monolith.
kasabali 4y ago
See related : "Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019)" https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 (also see dang's comment who lists 2 more thread https://news.ycombinator.com/item?id=32213973 https://news.ycombinator.com/item?id=32213973) Parent comment is downvoted but it seems like most alzheimer's researchers have vested interest in amyloid hypothesis one way or the other.

ncmncm 4y ago

civilized 4y ago
Jumping to conclusions again? Beware of confident cynicism as a substitute for technical expertise.
- orlp 4y ago
  It's absolutely jumping to conclusions, but so is blindly believing the people saying that the impact of it is low, when those very people are the authors which would be impacted. I'd say we'll have to wait and see.
  - civilized 4y ago
    I agree. It's a technical question at this point, and with all the attention now on it, there seem to be favorable conditions for a thorough investigation.
    - ncmncm 4y ago
      That is not what I got from the comments there. What I got was "damn the torpedoes, full speed ahead on amyloids!" When it is finally proven that interfering with amyloid synthesis never has any desirable effect of any kind, what will these people do instead of fooling with them?
      - civilized 4y ago
        This is a bit against Hacker News rules so I'm going to say this once and only once. You run around commenting on many diverse fields that no single human could possibly be an expert on simultaneously. These comments come with a consistent attitude: your position is obviously right, and only evil or self-interested establishments stand in the way of that being acknowledged. There are many other human beings who are just as smart as you or smarter, and just as invested in truth and goodness. Is it likely that you have the royal road to these things?

civilized 4y ago

I agree, the discussion here is reassuring. This may just be a case of a fraudulent paper piggybacking on an otherwise credible research program focusing on amyloid oligomers - not the plaques which recent failed therapies have targeted, and which many of these researchers knew were poor targets for decades before the FDA debacle over aducanumab. We can blame regulatory capture of the FDA for approval of failed drugs, rather than the scientific establishment. And we can blame Sylvain Lesné for Sylvain Lesné's fraud. I would encourage those of us whose only knowledge of this topic is the word "amyloid" (I admit I am one of them) to read the scientists' comments and appreciate that there is more to this than we know. There are complexities, nuances, diverse perspectives and healthy disagreements. It's not just a political battlefield. Projecting culture war into it would be harmful to the scientific progress we all value and to the millions who suffer from Alzheimer's.

koheripbal 4y ago
Their comments are not without self-interest. They all see the potential of their own funding being re-evaluated if they admit that any of their ongoing research build's on (or even references) Sylvain Lesné's work. They have an interest in limiting the scope of the perception of fraud in the field.
- civilized 4y ago
  And the people who want a change in direction have an interest in calling out any of that sort of thing that may be happening. So if it is, I hope to see it called out in a scientifically substantial way.

kasabali 4y ago

I recommend reading these instead: Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=31828509 How an Alzheimer’s ‘cabal’ thwarted progress toward a cure https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 The amyloid hypothesis on trial https://news.ycombinator.com/item?id=17618027 https://news.ycombinator.com/item?id=17618027 Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) https://news.ycombinator.com/item?id=17444214 https://news.ycombinator.com/item?id=17444214 Why, at this point should we believe any one scientist writing in that forum wasn't already sunk far deep into amyloid research in their career? Not to mention that after a quick glance on the comments section, I fail to see where you get the idea that "They all disagree with the notion that Lesné's papers have been important to the field". Apart from the very first comment from karen Ashe (who will obviously be defending her research) and a few other who's working on related topics, other commenters seems to be keeping their suspicion at amyloid hypothesis.

user1337331 4y ago
Rather than just scrutinizing a single hypothesis for AD we must understand that it is a multi factorial disease and that there are other hypotheses as well (i.e., acetylcholine, tau, transport-clearance), which affect and complicate this disease. Furthermore, we know very little about the brain, hence why novel therapies consistently fail in the clinic compared to other diseases (i.e., cancer). Most of these antibodies that target amyloid don’t even cross the blood-brain barrier (<0.1% and need an effective dose of 1000x blood-plasma for effective amyloid lowering) - provided with this, can we really attest the failure of the amyloid hypothesis? Moreover, the commenters there are big names in the AD community