5 ms·

The last thing I read about the link between amyloid-β accumulation and Alzheimer's was that the entire field was full of fake data ( https://www.science.org/co

The last thing I read about the link between amyloid-β accumulation and Alzheimer's was that the entire field was full of fake data ( https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean https://www.science.org/content/blog-post/faked-beta-amyloid... ). In particular, even treatments that directly reduce amyloid-β in the brain did not restore cognitive abilities. At least this paper tests both cognitive abilities as well as "amyloid-β pathologies." I'm not at all an expert in this field but gold nanoparticles sounds like something you'd see on a late night infomercial, lol.

Etheryte 3y ago
Don't worry, it's not just this field, roughly 70% of medical studies are fake or severely flawed [0]. [0] https://news.ycombinator.com/item?id=37572394 https://news.ycombinator.com/item?id=37572394
- mft_ 3y ago
  That may or may not be the case, but you're rather detracting from the original comment, either deliberately or not. The issue in the Alzheimer's world is the possibility that the very disease mechanism concept underlying the vast majority of research and interventional trials into which countless multiple billions have been poured, is incorrect. Within that space, this is orders of magnitude more fundamental and serious than a flip aside that lots of trials have problems, so who cares about another?
  - epistasis 3y ago
    > the very disease mechanism concept underlying the vast majority of research and interventional trials into which countless multiple billions have been poured, is incorrect. Not "is incorrect," but might be incorrect. And we almost certainly won't know it is correct until we actually have a therapy. Those pursuing cures could have waited until there was more solid science, but they and their funders took on the risk, knowing full well that the amyloid hypothesis is not proven. This is not some indictment of science, this is normal risk taking for a problem that hugely affects society.
    - smolder 3y ago
      > Not "is incorrect," but might be incorrect. That's why the part you quoted is preceded by "the possibility that".
      - epistasis 3y ago
        But the entire framing of the comment is that the amyloid hypothesis is taken as fact and not possibility, when in fact the core research question is whether it is true or not. It is the best possible explanation so far, but four decades of research have not reached a definitive conclusion. An open problem is not a problem for science, that's the fundamental focus of science. The problem is people misrepresenting what science is and what it aims to do.
        mft_ 3y ago
        (Late back to this but) It's far more skewed than you're making out. That the a-beta hypothesis is true, is/was the vastly dominant prevailing belief in the field, to the extent that it hasn't been a question that many 'experts' were willing to meaningfully address. To be clear: for decades, researchers wishing to pursue lines of inquiry contrary to the a-beta hypothesis struggled for traction and funding, and saw their careers struggle as a result[0]. As such, trying to disprove the a-beta hypothesis was not the core research question for many/most, for long time. [0] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/ https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...
        epistasis 3y ago
        (Edit: forgot to say, thanks for continuing the conversation, it is much appreciated! This comment may come across snippier than I intended, but please know I appreciate your effort here even though my experiences lead me to a different conclusion.) This article is just sensationalization of the standard scientific process. Grants do get awarded by friends and it does appear very much like a cabal. Or things like this: > A top journal told one that it would not publish her paper because others hadn’t. Oh the horror, not getting published in a top journal! Turns out that most good science gets published outside the top journals. This sort of behavior is bad, and has always been part of the process, and may actually be better today than it was a century ago, as the clubs are not nearly so tight as they were back then. Early in my career I remember reading some of ET Jaynes' (an early Bayesian reasoning guy) discussions of his early career, and how he had to very very carefully choose his topics so that he wouldn't upset the big personalities in physics and thereby have his entire career crushed. It's better these days than it was then! There will be sour grapes about funding, just as there are when VCs all jump on the hype train for the same idea, but my only scientific exposure to the amyloid hypothesis for the past 20 years has been in terms of it being an unproven hypothesis. Starting down exploratory routes for explanatory hypotheses should have been pursued, and was pursued, and will continue to be pursued, but the question of "how much" is exceptionally difficult to answer. Perhaps I'm biased from being in Science too long, but I've seen so many sensational Stat News article that never pan out when pushed upon. I wouldn't trust them at all with stuff like this.
- InSteady 3y ago
  Ah, the game of telephone. >For more than 150 trials, Carlisle got access to anonymized individual participant data (IPD). By studying the IPD spreadsheets, he judged that 44% of these trials contained at least some flawed data: impossible statistics, incorrect calculations or duplicated numbers or figures, for instance. And in 26% of the papers had problems that were so widespread that the trial was impossible to trust, he judged — either because the authors were incompetent, or because they had faked the data. Firstly, this is only from one journal, Anesthesiology. Second, the phrase "at least" indicates that while 44% had some amount of (presumably) flawed data, only 26% of the studies were bad enough to be judged fake or severely flawed by this one (admittedly esteemed) researcher in the field of anesthesiology. It's important to be skeptical and do your homework when you hear sweeping and/or shocking results. It's also important to read carefully, especially with science journalism because it is written for clicks and broad audiences, not to reduce ambiguity and adhere to strict standards of accuracy.
  - svnt 3y ago
    I didn’t go look up the quote but based on your version here it sounds like roughly half (44%) had some kind of suboptimality, and of those roughly a quarter (26%) had serious problems preventing them from being relied on. That means 11% of the total papers should be discarded, which means 89% of the papers can be used.
    - InSteady 3y ago
      As per usual, science reporting fails to use precise language. It can be interpreted either way, although I think your interpretation is the slightly larger leap based on phrasing. In any case, it is far below the 70% (and not directed broadly at all scientific research) that GP states.
      - svnt 3y ago
        I went and read the article but have not tracked down the original paper. It is at least 26%, because that was the percentage of studies that provided access to their data that proved faked or fatally flawed. It may be substantially higher.
instagraham 3y ago
It's hard to discern discourse in a field one is unfamiliar in, I'd tried with the Alzheimer's fiasco. Here's my tuppence: The plaques are known to be linked to Alzheimer's, the debunking of one paper that messed with its figures does not detract from the whole body of research. The inefficacy of plaque-targeting treatments may not be proof that the plaques are not causal in nature, only that their damage is not reversible/fully understood.
epistasis 3y ago
In a massive field, one researcher does not constitute "full of faked data," despite how concerning it is. The problem is viewing individual papers as the unit of truth in science. The "self-correcting" nature of science will actually reject entire papers, and entire directions of inquiry. Including, maybe, a casual relationship between beta amyloid and AD, but maybe not. The other key part of science is holding everything in a state of uncertainty. There's some "facts" but mostly just hints and clues. And with Alzheimer's disease in particular we are trying to make progress with completely inadequate vision; we really can't even measure so much of what we want to measure. Feynman said it back in the 1960s, too, physicists have failed to deliver the tools to biologists to really measure what needs to be measured. There have been advancements, and DNA sequencing technology in the past decade has been turned into the most clever sorts of information theoretic microscopy by combining DNA sequences with many other biochemical processes. But we as a species still can not measure a lot of the things we'd like to measure.
- epistasis 3y ago
  I wish to retract this comment, as it was not based on full information. I was going off of the data fr the linked article, but here are many more cases of fraud from leaders in the field: Marc Tessier-Lavigne https://stanforddaily.com/2023/02/17/internal-review-found-falsified-data-in-stanford-presidents-alzheimers-research-colleagues-allege/ https://stanforddaily.com/2023/02/17/internal-review-found-f... Berislav Zlokovic https://www.science.org/content/article/misconduct-concerns-possible-drug-risks-should-stop-stroke-trial-whistleblowers-say https://www.science.org/content/article/misconduct-concerns-... Hoau-Yan Wang https://www.science.org/content/article/co-developer-cassava-s-potential-alzheimer-s-drug-cited-egregious-misconduct https://www.science.org/content/article/co-developer-cassava... Sylvain Lesné - the researcher from grandparent comment's article This list taken from Chris Said on Twitter https://x.com/chris_said/status/1724448550493315436?s=46 https://x.com/chris_said/status/1724448550493315436?s=46
- SubiculumCode 3y ago
  A most eloquent response that needed to be said.
- 3y ago
Aurornis 3y ago
> In particular, even treatments that directly reduce amyloid-β in the brain did not restore cognitive abilities. Correct, but this doesn’t constitute “fake data”. It could be that amyloid-β is a marker rather than a causative factor. Or it could be that amyloid-β related damage is downstream, and remove amyloid-β after the damage has been done won’t remove the other damage. It’s too quick to wave away an entire field because a single theory didn’t pan out. Most medical research proceeds with a lot of dead ends before it is figured out.
- xitrium 3y ago
  Very true, but it seems like you may not have seen the expose on this field in Science https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio...

Etheryte 3y ago

Don't worry, it's not just this field, roughly 70% of medical studies are fake or severely flawed [0]. [0] https://news.ycombinator.com/item?id=37572394 https://news.ycombinator.com/item?id=37572394

mft_ 3y ago
That may or may not be the case, but you're rather detracting from the original comment, either deliberately or not. The issue in the Alzheimer's world is the possibility that the very disease mechanism concept underlying the vast majority of research and interventional trials into which countless multiple billions have been poured, is incorrect. Within that space, this is orders of magnitude more fundamental and serious than a flip aside that lots of trials have problems, so who cares about another?
- epistasis 3y ago
  > the very disease mechanism concept underlying the vast majority of research and interventional trials into which countless multiple billions have been poured, is incorrect. Not "is incorrect," but might be incorrect. And we almost certainly won't know it is correct until we actually have a therapy. Those pursuing cures could have waited until there was more solid science, but they and their funders took on the risk, knowing full well that the amyloid hypothesis is not proven. This is not some indictment of science, this is normal risk taking for a problem that hugely affects society.
  - smolder 3y ago
    > Not "is incorrect," but might be incorrect. That's why the part you quoted is preceded by "the possibility that".
    - epistasis 3y ago
      But the entire framing of the comment is that the amyloid hypothesis is taken as fact and not possibility, when in fact the core research question is whether it is true or not. It is the best possible explanation so far, but four decades of research have not reached a definitive conclusion. An open problem is not a problem for science, that's the fundamental focus of science. The problem is people misrepresenting what science is and what it aims to do.
      - mft_ 3y ago
        (Late back to this but) It's far more skewed than you're making out. That the a-beta hypothesis is true, is/was the vastly dominant prevailing belief in the field, to the extent that it hasn't been a question that many 'experts' were willing to meaningfully address. To be clear: for decades, researchers wishing to pursue lines of inquiry contrary to the a-beta hypothesis struggled for traction and funding, and saw their careers struggle as a result[0]. As such, trying to disprove the a-beta hypothesis was not the core research question for many/most, for long time. [0] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/ https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...
        epistasis 3y ago
        (Edit: forgot to say, thanks for continuing the conversation, it is much appreciated! This comment may come across snippier than I intended, but please know I appreciate your effort here even though my experiences lead me to a different conclusion.) This article is just sensationalization of the standard scientific process. Grants do get awarded by friends and it does appear very much like a cabal. Or things like this: > A top journal told one that it would not publish her paper because others hadn’t. Oh the horror, not getting published in a top journal! Turns out that most good science gets published outside the top journals. This sort of behavior is bad, and has always been part of the process, and may actually be better today than it was a century ago, as the clubs are not nearly so tight as they were back then. Early in my career I remember reading some of ET Jaynes' (an early Bayesian reasoning guy) discussions of his early career, and how he had to very very carefully choose his topics so that he wouldn't upset the big personalities in physics and thereby have his entire career crushed. It's better these days than it was then! There will be sour grapes about funding, just as there are when VCs all jump on the hype train for the same idea, but my only scientific exposure to the amyloid hypothesis for the past 20 years has been in terms of it being an unproven hypothesis. Starting down exploratory routes for explanatory hypotheses should have been pursued, and was pursued, and will continue to be pursued, but the question of "how much" is exceptionally difficult to answer. Perhaps I'm biased from being in Science too long, but I've seen so many sensational Stat News article that never pan out when pushed upon. I wouldn't trust them at all with stuff like this.
InSteady 3y ago
Ah, the game of telephone. >For more than 150 trials, Carlisle got access to anonymized individual participant data (IPD). By studying the IPD spreadsheets, he judged that 44% of these trials contained at least some flawed data: impossible statistics, incorrect calculations or duplicated numbers or figures, for instance. And in 26% of the papers had problems that were so widespread that the trial was impossible to trust, he judged — either because the authors were incompetent, or because they had faked the data. Firstly, this is only from one journal, Anesthesiology. Second, the phrase "at least" indicates that while 44% had some amount of (presumably) flawed data, only 26% of the studies were bad enough to be judged fake or severely flawed by this one (admittedly esteemed) researcher in the field of anesthesiology. It's important to be skeptical and do your homework when you hear sweeping and/or shocking results. It's also important to read carefully, especially with science journalism because it is written for clicks and broad audiences, not to reduce ambiguity and adhere to strict standards of accuracy.
- svnt 3y ago
  I didn’t go look up the quote but based on your version here it sounds like roughly half (44%) had some kind of suboptimality, and of those roughly a quarter (26%) had serious problems preventing them from being relied on. That means 11% of the total papers should be discarded, which means 89% of the papers can be used.
  - InSteady 3y ago
    As per usual, science reporting fails to use precise language. It can be interpreted either way, although I think your interpretation is the slightly larger leap based on phrasing. In any case, it is far below the 70% (and not directed broadly at all scientific research) that GP states.
    - svnt 3y ago
      I went and read the article but have not tracked down the original paper. It is at least 26%, because that was the percentage of studies that provided access to their data that proved faked or fatally flawed. It may be substantially higher.

instagraham 3y ago

It's hard to discern discourse in a field one is unfamiliar in, I'd tried with the Alzheimer's fiasco. Here's my tuppence: The plaques are known to be linked to Alzheimer's, the debunking of one paper that messed with its figures does not detract from the whole body of research. The inefficacy of plaque-targeting treatments may not be proof that the plaques are not causal in nature, only that their damage is not reversible/fully understood.

epistasis 3y ago

In a massive field, one researcher does not constitute "full of faked data," despite how concerning it is. The problem is viewing individual papers as the unit of truth in science. The "self-correcting" nature of science will actually reject entire papers, and entire directions of inquiry. Including, maybe, a casual relationship between beta amyloid and AD, but maybe not. The other key part of science is holding everything in a state of uncertainty. There's some "facts" but mostly just hints and clues. And with Alzheimer's disease in particular we are trying to make progress with completely inadequate vision; we really can't even measure so much of what we want to measure. Feynman said it back in the 1960s, too, physicists have failed to deliver the tools to biologists to really measure what needs to be measured. There have been advancements, and DNA sequencing technology in the past decade has been turned into the most clever sorts of information theoretic microscopy by combining DNA sequences with many other biochemical processes. But we as a species still can not measure a lot of the things we'd like to measure.

epistasis 3y ago
I wish to retract this comment, as it was not based on full information. I was going off of the data fr the linked article, but here are many more cases of fraud from leaders in the field: Marc Tessier-Lavigne https://stanforddaily.com/2023/02/17/internal-review-found-falsified-data-in-stanford-presidents-alzheimers-research-colleagues-allege/ https://stanforddaily.com/2023/02/17/internal-review-found-f... Berislav Zlokovic https://www.science.org/content/article/misconduct-concerns-possible-drug-risks-should-stop-stroke-trial-whistleblowers-say https://www.science.org/content/article/misconduct-concerns-... Hoau-Yan Wang https://www.science.org/content/article/co-developer-cassava-s-potential-alzheimer-s-drug-cited-egregious-misconduct https://www.science.org/content/article/co-developer-cassava... Sylvain Lesné - the researcher from grandparent comment's article This list taken from Chris Said on Twitter https://x.com/chris_said/status/1724448550493315436?s=46 https://x.com/chris_said/status/1724448550493315436?s=46
SubiculumCode 3y ago
A most eloquent response that needed to be said.
3y ago

Aurornis 3y ago

> In particular, even treatments that directly reduce amyloid-β in the brain did not restore cognitive abilities. Correct, but this doesn’t constitute “fake data”. It could be that amyloid-β is a marker rather than a causative factor. Or it could be that amyloid-β related damage is downstream, and remove amyloid-β after the damage has been done won’t remove the other damage. It’s too quick to wave away an entire field because a single theory didn’t pan out. Most medical research proceeds with a lot of dead ends before it is figured out.

xitrium 3y ago
Very true, but it seems like you may not have seen the expose on this field in Science https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio...