20 ms·

Potential fabrication in research threatens the amyloid theory of Alzheimer’s

• tmaly 4y ago
  Yes, that is a lot of grant money to waste, but I think the biggest loss here is 16 years of research in the wrong direction.
  • deleted 4y ago
    [deleted]
  • nabla9 4y ago
    Intentionally diverting resources and skewing research from one of the most biggest growing epidemics of our time seems seems like huge crime against humanity that has not been criminalized yet.
    • johndhi 4y ago
      hehe, ironically diverting resources and skewing research and overall making worse the biggest PANDEMIC of our time isn't a crime at all :)
      • dang 4y ago
        "Eschew flamebait. Avoid unrelated controversies and generic tangents." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
    • legulere 4y ago
      Alzheimer isn’t a growing epidemic. The incidence is going down.
      • Dylan16807 4y ago
        Enough to compensate for population growth?
      • nabla9 4y ago
        On a global scale, Alzheimer’s is growing epidemic. The age adjusted mortality is declining in some countries, but when boomer generations age, the number of cases increases.
    • deleted 4y ago
      [deleted]
    • upwardbound 4y ago
      Agree. The perpetrator should go to prison for some sort of criminal fraud or racketeering or whatever a prosecutor can apply. This is serious crime.
      • Ekaros 4y ago
        Also anyone who used the results without sufficient due diligence should be barred from working as researcher or receiving grant money. They are not quilt free either.
        • schnitzelstoat 4y ago
          What is due diligence though? Are they supposed to do a forensic analysis of every paper they cite? It's sad if it's arrived to this point. Reproducing the original result can be prohibitively expensive and difficult in many fields (ideally, this wouldn't be a concern - but generally, research groups aren't rolling in cash and resources, plus you need to be fast not to get scooped for the next paper and lose future grant money)
          • SturgeonsLaw 4y ago
            Given the replication crisis, more questions should be asked. Everyone knows a disturbingly large number of papers are on shaky foundations, but nobody is good at picking which ones
        • dash2 4y ago
          Steady on now. Scientists rely on each other, they're not supposed to be fraud investigators.
        • evandijk70 4y ago
          What about a researcher that measures the kinetics of AB-aggregation in vivo, performs X-Ray crystallography to determine the structure of this (or another amyloid), or performs simulations to determine free binding energies of various antibodies with the oligomer and cites this paper as the reason it has clinical relevance? I know people in the field that do all this kind of research and do not know much about mice-experiments or even about the experimental techniques used to obtain these results. To me, they are victims of this fraud more than anything.
  • permo-w 4y ago
    based on the comments from alzforum, the relevant academics do not see this as 16 years of research in the wrong direction. they seem to see it as an invalidation of one branch of the research, while the overarching theory is still intact the cynic in me suspects that they're saying that to maintain their - presumably funded - status quo, but not being even remotely knowledgeable in the subject, I have no idea whether that is well-founded
• snapetom 4y ago
  Holy hell. Someone please correct me, but the beta-amyloid camp has been under attack, establishment researchers still keep going despite weak evidence, and now the best drug they have might have fabricated data???
  • resoluteteeth 4y ago
    Nope. It wasn't evidence for a drug that was fabricated, it was a 2006 study published in Nature that convinced everyone to believe the amyloid hypothesis.
    • JPLeRouzic 4y ago
      > * it was a 2006 study published in Nature that convinced everyone to believe the amyloid hypothesis.* The amyloid hypothesis is one century old.
      • dekhn 4y ago
        No, it's not. It was introduced in the 90's. "The amyloid hypothesis was first proposed in 1991 by John Hardy and David Allsop." You're probably thinkinng of the person who "discovered" Alzheimer's disease (Alois Alzheimer).
• jamiek88 4y ago
  Oh my god if true, and it looks to be true this is huge. The amyloid beta (Aβ) hypothesis has always been fishy but this paper is basically the bedrock of the current investigational trajectory. The Aβ hypothesis was almost dead in 2006 when this method was invented and results posted and it sent shockwaves through the research world. Since then spending on Aβ research by NIH has gone from $0 to $290 million all it seems based on a lie cited over 2000 times in further papers. The article is pretty convincing as is the independent verification that not only concurred but found additional evidence. Sylvain Lesne has some ‘splainin to do.
  • phkahler 4y ago
    >> it seems based on a lie cited over 2000 times in further papers. Since papers tend to get published only if they have positive results, what does it mean for thousands of publications all citing a fraudulent paper? This seems really strange. If the first 1000 failed to produce results and were partially based on that original paper it should cast significant doubt on it, but again failures are rarely published. What does this mean then?
    • api 4y ago
      Citation doesn't mean dependency. It just means the paper was mentioned. What it does mean is that each and everyone of those papers must be re-examined with extra scrutiny to see if they hold up without the cited paper.
    • BoorishBears 4y ago
      That's why it was described as a "bedrock". A lot of papers that came after were producing results in the framework it established. Because of the nature of a disease like Alzheimer's not many studies can easily measure the final effectiveness of their addition to the space on patients.
    • derbOac 4y ago
      To me this is one of the most damning things about this: all the people citing these papers and probably burying negative results. Yes, fraud is unacceptable, but what about all the people using it to further their careers? These types of cases tend to focus on the fraud, but then everyone eventually walks away and then there's no larger discussion of how this was enabled by the field to have such a hold. I don't buy the idea that it's all so quixotic and involves so many variables to get right that who knows what's causing a lack of replication. I've heard whispers like this about other big effects in other fields. People know what's going on, and often it's right there in published results but ignored.
• JPLeRouzic 4y ago
  This guy might well have cheated but how could he be responsible for the huge mess which is the amyloid-β research (and amyloid-β lobby as told by Statnews [0])? Sylvain Lesné, has no Wikipedia page. He seems to publish roughly a paper per year while some famous scientists publish one every month. He is not at the origin of the amyloid-β hypothesis which is more than 100 years old. Even more there are thousand papers published about Aβ*56 and Alzheimer's disease. How could this guy responsible for this mess? And if what he published was wrong, why this was discovered only 18 later if thousands scientists are working in the field? My understanding is that there is a need to find a scapegoat for the amyloid-β and pointing to an obscure guy is in the interest of many big fish. [0] https://www.statnews.com/2019/05/21/alzheimers-disease-amyloid-hypothesis-history/ https://www.statnews.com/2019/05/21/alzheimers-disease-amylo...
  • fabian2k 4y ago
    As far as I understand this is not about the Aβ hypothesis itself, but the toxic oligomer hypothesis.
  • spfzero 4y ago
    The OA points out it was, or was one of, the most cited papers in subsequent AB research. They make the argument that it has mislead many other researchers and cause a waste of many millions in funding. He's not an obscure guy in the field of AB research.
    • dralley 4y ago
      That's precisely why it should have been caught earlier.
    • xigency 4y ago
      So the observations it made were pivotal to expanding research, but none of the following studies discovered counter-evidence? It seems like something is missing here.
  • jibe 4y ago
    Even more there are thousand papers published about Aβ56 and Alzheimer's disease. How could this guy responsible for this mess?* Because he started it? https://www.nature.com/articles/nature04533 https://www.nature.com/articles/nature04533 But it is ultimately in indictment of everyone who went along unskeptically, collecting grant money.
• elliekelly 4y ago
  What (if any) recourse is there against those who have falsified scientific data? It almost feels like fraud on the {scientific research} market. Billions of dollars and, perhaps even worse, countless human hours, have been wasted in reliance ob completely fabricated information. For what? An ego boost? Citations? I don’t work in science so I truly don’t understand the motive(s) on the other side of the equation.
  • dormento 4y ago
    And people who might've benefited from an actual, more reliable treatment who might have been developed, had the scientist refocused to other hypotheses. This is infuriating.
  • MattGaiser 4y ago
    Presumably the same incentives as everywhere else. Money.
    • hackerlight 4y ago
      Personal gain, whether that's money or status, at the expense of other people.
  • derbOac 4y ago
    This is so typical of contemporary academics, at least in biomedicine, I don't know where to start. For me, this is exemplary of a lot of what I see in the field, that happens every day, to larger or smaller degrees. It's not the exception. There's so many elements to this story that echo things I've encountered, and read about in studies of trends. For every case of outright fraud like this might be, there's dozens of "soft fraud" (read: "questionable research practices") that get the benefit of the doubt or are never brought to light. No one has discussed this here yet, but part of the story is that the program officer on one of the accused' recent grants was a coauthor with him on this very research -- consistent with trends discussed in the literature (of the largest predictor of grant receipt being coauthoring papers with grant review panel members or officers). So there's this fraud, potentially involving someone who then goes on to help decide who gets research dollars. Your reaction is something I've wrestled with a lot. Many times there are no consequences really. People talk about lost reputation or something, but in cases of soft fraud nothing really happens. It just all kind of evaporates into a fog of scientific dispute between parties. In cases of blatant, legal fraud, someone can be fired or lose a position, but that requires significant evidence. For what? Yes, ego, citations, money, titles, accolades as a "rising star" or a "genius" or whatever it is. The saddest thing to me really, aside from all those harmed by bogus treatments, or forgoing real treatments, is all the researchers with legitimate ideas, who go against trend, who are pushed out because doing the hard work isn't glitzy and has lots of dead ends. You end up in this system where the buzz is what matters, and riding waves of self-perpetuating hype is what gets you to the top. Appropriate skepticism and careful thought, meanwhile, costs you because that takes time and risk.
• fabian2k 4y ago
  When I started reading the article I thought the title was a bit click-baity for Science. But then I noticed that the theory it refers to was not the amyloid hypothesis itself, but the toxic oligomer hypothesis that emerged later. That theory is pretty much the main potential explanation on why every single drug targeting Aβ failed that still keeps Aβ fibrils relevant. It's a very convenient theory because it keeps the main original observations about the fibrils relevant while explaining why therapies that target them don't work. One part that is really important that is mentioned in the middle of the article is that these systems are very difficult to handle, and it's almost impossible to make many of them nicely reproducible. Fibril and oligomer formation depends a lot on the environment and reacts to tiny differences. I find this kind of fraud deeply frustrating, there is so much wasted effort in the wake of faked high-profile results.
  • chmod600 4y ago
    "very difficult to handle, and it's almost impossible to make many of them nicely reproducible" Those same qualities that make a study hard to reproduce should also create skepticism that the first study was done properly.
    • fabian2k 4y ago
      It's more insidious than that. In a field where the core subject is difficult to handle it is nothing unusual if a different lab cannot recreate known experiments on their first try. This doesn't mean anything is wrong with the original research, it might just mean that the second lab didn't control all the variables. The part that is difficult and annoying is that the variables are not necessarily known, it takes a lot of time and experiments to actually nail down those. And even then for some sensitive stuff every detail can matter, like the exact type of tube you did the experiment in or the vendor, batch and age of every chemical you used. Very often you can control this enough to have consistent results for a set of experiments, but that kind of stuff is really hard to control across different labs.
      • LudwigNagasena 4y ago
• chmod600 4y ago
  Proposal: if a paper isn't reproduced in ten years after publication, then it gets automatically retracted (which can be reversed as soon as it is reproduced). Any papers that cite the retracted study (in a way that the conclusions depend on it) would also get retracted. That would be powerful incentive for all the researchers who cite the study to try and reproduce it so their papers don't get retracted. You could still search these retracted studies when doing research, of course. You just can't cite them.
  • axg11 4y ago
    This is a powerful idea. Most problems in science are incentives problems. Sadly there's little or no incentive for journals to adopt this policy.
    • cjmb 4y ago
      I agree. Correcting the many incentive problems in modern American science would need a hypothetical body with significant funding leverage over journals & scientists to exert executive action. Sadly there is no such centralized funding body, so the problem must be unsolvable.
  • anakaine 4y ago
    The same issues exist. The next dodgy scientist on the hamster wheel looking to get a name for themselves will claim reproducibility and then publish a follow up in the spirit of publish or perish. You could further entrench the issue with this approach, unfortunately.
    • lamontcg 4y ago
      Better solution might be for the government to just fund reproducibility studies, and even departments of reproducibility. Take the profit motive out of it, find good scientists who are painstaking but maybe not innovative and fund them to reproduce major results. The scientists would never get the credit for major breakthroughs, but could occasionally be wrecking balls that called research like this into question. With consistent and reliable funding from the government their reward could be stability of employment rather than innovative fame (of course these days some partisan politics would probably gut it, which is why we can't have nice things).
• macinjosh 4y ago
  FTA: "“So much in our field is not reproducible, so it’s a huge advantage to understand when data streams might not be reliable,” Schrag says." I am just a lowly engineer, but this alarms me. Why is anything that has not been reproduced considered valid science by anyone? Why aren't our standards higher? If you can't reproduce an experimental result, it is useless information is it not? At least an experiment that can be reproduced yet fails to prove a hypothesis can teach you something. An experiment that cannot be reproduced yields no useful information. In fact, it can even mislead! I just don't understand the motivations at play. These are obviously intelligent people who know that you can't fake reality, so why do they publish fraudulent papers? Just for short-term gain? Do they become blinded by belief in their hypothesis?
  • ncmncm 4y ago
    They are blinded by assuming good faith and competence. Most scientists consider most of their colleagues more or less incompetent, and even where they accept experimental results, often reject the experimenter's interpretation of the result, often correctly. Scientists advise us to ignore the abstract, ignore the interpretation, ignore the conclusion, and trust only the data, at most. But we mostly don't get to do that for fields not our own. High prestige is detrimental in that it short-circuits this skepticism. This happens not only in Alzheimer Syndrome work. It put psychology research in the grip of behaviorism, statistics in the grip of non-causality, political science in the grip of dialectics.
  • niemandhier 4y ago
    Biological systems are so complex that reproducing results is extremely hard even if the authors publish their method in detail, simply because they might not know why it works for them. This is hard to understand for software people, since code tends to behave reproducible as a default. Basically the only way to reproduce a difficult finding is to learn the procedure at the original lab. An example: A friend of mine could not reproduce his own findings in another lab. Turned out the precise type of the lamp build into the setup mattered. Another example: I could not reproduce a finding the was something I wanted to build upon. Turned out the precise method to dissolve one of the chemicals in the buffer as the problem. It was even hinted in the paper, but who would describe in detail what he means by “ vigorously stirred” ?
• axg11 4y ago
  The most powerful results in science are continually reproduced by being built upon to uncover further new knowledge. I'm no expert in the toxic oligomer hypothesis or Aβ hypothesis, but it appears that these paths have led to very little new knowledge.
  • api 4y ago
    It reminds me of the eating cholesterol hypothesis for artery blockage and heart disease. Most artery blockages are made of cholesterol therefore eating cholesterol must be the culprit. Simple, straightforward, and now apparently wrong. The cholesterol buildup is a symptom of something else. Seems likely with Alzheimers that the amyloid buildup is a symptom not a cause.
  • ramraj07 4y ago
    Still half a billion dollars of NIH money went into this sub field. The article points to how the main accused got an R01 approved AFTER this misconduct started to come out, and the guy awarding it was one of the coauthors of the first fabricated papers.
• ta8645 4y ago
  There is so much of this, through many fields of science today. Incentives that corrupt and undermine the scientific method. And yet, many people will deny that there is justification in skepticism of say, relatively new mRNA vaccines. Yes, it's good that science usually deals with such problems in the long run, but how is the average person supposed to trust that the latest scientific assurance, isn't 15 years away from being retracted like in this example?
  • JulianMorrison 4y ago
    A big part of the problem is things moving so fast that a lot of stuff doesn't have a long run. Covid and its vaccines being an example. In the end the reason to trust them was a mix of "if not this, then what?" and "it doesn't seem to be killing people".
    • fabian2k 4y ago
      We have a lot of really good evidence that the vaccines are preventing a lot of deaths.
      • ncmncm 4y ago
        It has been unfortunately necessary to downplay cases of debilitation and, even, death apparently traceable to vaccination. If vaccination saves the lives of a hundred times as many people as it harms, in the "trolley" sense, that should be good enough, but in popular imagination it is not. Rational treatment might enable identifying individuals particularly at risk and not vaccinating those, but that option is closed to us. Instead, a random, suspicious fraction of the population pays particular attention to negative outcomes and avoids vaccination, to its detriment, and most of those at risk for problems get vaccinated anyway.
        • ta8645 4y ago
          > It has been unfortunately necessary to downplay cases of debilitation I don't think it was necessary at all, and instead is very counterproductive. Many people know they're not being dealt with honestly by the government and media, resulting in more distrust and resistance to vaccination, than there otherwise would be.
• upsidesinclude 4y ago
  This is what makes statements like "trust the science" so sickening. Science isn't religion and it isn't always honest
  • ncmncm 4y ago
    The science is only more reliable than non-science, not reliable in any absolute sense. And scientists are as fond of superstition as anybody. Masks were described as useless for countering COVID transmission because of what turned out to be superstition around "airborne transmission", itself finally traced to a result that properly only applied to tuberculosis. Belief in ivermectin efficacy was a similarly widespread superstition among mostly non-scientists. We have generally had much better results from science. Science was finally obliged to abandon its "airborne transmission" model by people who knew better publicizing correct information. But most ivermectin fans still cling to it.
    • m348e912 4y ago
      You have to think that this type of news does add ammo for climate science deniers, covid vaccine skeptics, and ivermectin/hcq proponents to make the case consensus science != absolute science. Regardless, I do think most people agree that all science should have the opportunity to be subjected to earnest and thoughtful scrutiny, and it shouldn't be a career ending endeavor to do so.
      • ncmncm 4y ago
        Sorry, what "news" do you cite here? Are you referring to hypothetical publication of adverse reaction numbers, and speculation about those numbers?
    • throwawaylinux 4y ago
      > The science is only more reliable than non-science, not reliable in any absolute sense. What "the" science? The scientific method is proven to be a very good way to make predictions about the world based on observations. The body of scientific work built up is immeasurably valuable and incredibly good at predicting things. Some random corporation or politician or person claiming to have The Science on their side, and that anybody who disagrees or questions them is a heretic and an unbeliever? That's not reliable and it's not science.
• ThePhysicist 4y ago
  Reminds me of that famous paper about Majorana fermions [1] that got retacted because they edited a figure (I'd say with malice) to support their sensationalist claim. In the unedited image the claimed effect is all but gone. The publication of the paper led to a flurry of research funding and a partnership with Microsoft (who were keen on using Majorana fermions for topological quantum computing). 1: https://physicsworld.com/a/retraction-of-nature-paper-puts-majorana-research-on-a-new-path/ https://physicsworld.com/a/retraction-of-nature-paper-puts-m...
• ChrisMarshallNY 4y ago
  I remember the story about the addiction "study" ("Porter Jick") that was used as the basis for declaring OxyContin "non-addictive." It was dramatized (but fairly accurately) in Dopesick. It was a letter to the editor, by a doctor, describing a small study on hospitalized patients, and was seized upon by Purdue, as the basis for their entire sales pitch. When there's money to be made, people can look the other way, quite easily.
  • schnitzelstoat 4y ago
    "It is difficult to get a man to understand something when his salary depends upon his not understanding it." - Upton Sinclair
• jajag 4y ago
  > Ashe declined via email to be interviewed or to answer written questions posed by Science ... But she wrote, “I still have faith in Aβ*56,” Richard Dawkins won't be impressed.
  • LeonB 4y ago
    I felt like the author’s choice to quote that specific part of whatever she wrote was a pretty harsh choice. As a reader you see that and jump to the exact conclusions you’re alluding to here.
• f38zf5vdt 4y ago
  There are so many correlations of vascular injury with dementia that it seems obvious that the fibrils would not be causative but rather correlated to dementia. I personally believe that dementia is related to or caused by repeated small vascular injuries that eventually cause degradation of the brain. That is, transient ischemic attacks that are completely subclinical aside from the injury that is visible after autopsy.
• dang 4y ago
  Related: How an Alzheimer’s ‘cabal’ thwarted progress toward a cure - https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 - Dec 2019 (382 comments) The amyloid hypothesis on trial - https://news.ycombinator.com/item?id=17618027 https://news.ycombinator.com/item?id=17618027 - July 2018 (43 comments) Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) - https://news.ycombinator.com/item?id=17444214 https://news.ycombinator.com/item?id=17444214 - July 2018 (109 comments)
• lightup 4y ago
  At the U of MN? Say it ain't so. My proud alma mater. Hacking linux kernel. Round up. Someone should start a list of what tax dollars pay for.
• mekoka 4y ago
  Reminiscent of this equally upsetting article a couple of years ago https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225
• cleandreams 4y ago
  Just to note the human cost, my father died of Alzheimers. It's not impossible this fraud prevented lives from being restored and even saved.
• onionisafruit 4y ago
  What makes me the most angry about this is the huge difference between what the scientist personally gained from this fraud and the cost of believing in these results for that past 16 years. Maybe he is a bit richer because of this, but it comes at the cost of hundreds of millions of dollars being spent on research that is destined to be fruitless. In the time since he published, I lost my father after investing hope that a trial that is supposed to prevent amyloid plaques and now my mother-in-law is slipping further into dementia.
  • nextos 4y ago
    As an insider, I am tempted to say research in most diseases is driven by lots of fraudulent and oversold results. Maybe not direct image manipulation as in this case with Alzheimer's, but certainly there is always a lot of monopolistic rich-gets-richer behavior. Nearly all professors at top universities I have met develop intimate relationships with funders and journals, which they use to steer the field in their preferred direction. As the posted article says "You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can't cheat to cure a disease." I have been asked directly to misrepresent results on several occasions. In the most recent one, a professor who has received all prizes and accolades in his field threatened me and others when we refused to misrepresent research results. I could afford to do this, but my workmates who have families to support were on the brink of giving up to the bully.
    • onionisafruit 4y ago
      Thank you for making a stand on this. My doctor has a "No Free Lunch" sign in his office saying he won't talk to pharmaceutical reps. Maybe the research side needs a similar pledge to avoid being corrupted by funding. I don't know what it would be though.
      • chevman 4y ago
        This is code that the price of entry at a minimum is an even more expensive dinner ;)
• mkl95 4y ago
  Is there any relevant (non-fabricated) research about the causes of fabrication in research? Is it just money or is there something else?
  • nomel 4y ago
    If it's anything like the data fabrication I've seen in industry, it's lack of ethics, laziness, mixed with deadlines/constraints beyond the individuals control, with a dash of arrogance that the conclusion is still correct, regardless, and it'll be fine. I've also seen very qualified people have a massive holes in their perception, making them somehow unaware that they're generating garbage, and even defending the garbage when it's pointed out.
• dmatech 4y ago
  And this is why I'm increasingly suspicious of "consensus" in the scientific establishment. With careers, egos, reputations, and grant money at stake, it's tempting to use one's power to entrench this consensus. Scientific consensus has value, but science also requires that people be open to having their pet theories be validated through replication.
  • epgui 4y ago
    I'm a scientist, and I don't think things so easily become consensus. In order to get to consensus, a model needs to have been tested from many different angles. It's never enough to get to statistical significance, things either get replicated or, more often, triangulated. Consensus is an extremely time-consuming thing to build, and it's extremely important to be aware of when there exists a consensus, where there isn't one, and what the consensus is. It isn't an appeal to authority fallacy, it's a form of deferral to expertise, and it's one of the most important heuristics we have.
    • ramraj07 4y ago
      Absolutely not true. I’ve seen things become consensus because of one single questionable image in one paper from a “trusted” lab. In my alma matter field the question was whether her2 receptor recycles (has implication of all breast cancer antibody therapies that target her2) and a paper from a Genentech lab had ONE FIGURE (where different data points from different experiments) as proof. An entire sub field including projects in my own lab were spawned assuming this. Whenever I point out this flaw in lab meetings I’d be shut down by my professors as “they know the authors they trust them”.
      • epgui 4y ago
        I think I'm going to continue disagreeing with you on this point, but I will point out that our difference of opinion is a semantic one. To say that everyone "believes in" a model could mean that everyone accepts it as plausible (and thus worthy of further exploration), or it could mean that everyone is justifiably certain that it maps properly to a real phenomenon. I never say that something is "consensus" in the first case: IMO, the term should be reserved for the latter case, or appropriately qualified. In any case, the situation you describe appears to lack meaningful triangulation. [1] [1] https://www.nature.com/articles/d41586-018-01023-3 https://www.nature.com/articles/d41586-018-01023-3
• smm11 4y ago
  Compare who has it, to who doesn't have it. My un-scientific version of this is that if you have a large bowl of ice cream for desert every night for 55 years, you may develop Alzheimer's Disease.
  • onionisafruit 4y ago
    I've never heard this before. The people I have lost to Alzheimer's were very healthy up to the point where the disease started manifesting.
    • smm11 4y ago
      https://www.cnn.com/2022/08/01/health/ultraprocessed-food-dementia-study-wellness/index.html https://www.cnn.com/2022/08/01/health/ultraprocessed-food-de...
• Archelaos 4y ago
  The article mentions that the main reason for suspecting that results were fabricated is that many images from the researcher's papers seem to have been manipulated. As someone who is not particularly familiar with AI but occasionally picks up on it here on HN, I am now wondering how difficult or easy it is these days to take a manipulated image of a western blot and feed it to an AI tool trained on unmanipulated western blots to create a deepfake that is then virtually indistinguishable from a true one. -- Can perhaps anyone here familiar with deepfake technology provide an assessment?
• Taniwha 4y ago
  I love how the researchers are shorting the stock - they're not insiders because the data is public available for anyone (with the requisite very domain specific knowledge) to see. There a whole lot of the sorts of investor who are normally shorting stuff who must feel that this is somehow insider information
• ta988 4y ago
  I worked in a lab doing research based on that amyloid hypothesis (working on other projects). The only thing that got out of it were molecules that were really good at messing up the assays used but had 0 biological effect in vivo. So in the end the lab optimized the protein and cell assays to make them were more sensitive to artifacts. This wasn't made on purpose, just a combination of human and institutional factors that combined as a perfect storm. Several dozens of academic papers were published on that... That's what happens when you have isolated labs in a university that doesn't favor and nurture collaborations but focuses instead on political and economical aspects. Now all the people that took the wrong decisions have either retired or got fancy positions elsewhere.
• kyaghmour 4y ago
  Patential link with diabetes: https://www.health.harvard.edu/blog/whats-the-relationship-between-diabetes-and-dementia-202107122546 https://www.health.harvard.edu/blog/whats-the-relationship-b...
  • pedalpete 4y ago
    "Potential" I work in the neurotech/sleeptech space, and specifically in stimulation of slow-wave oscillations. These SWOs decrease as we age, which is linked to the build-up of amyloid plaque, and increased insulin resistance. They aren't necessarily linked to each other, but rather to the decreased capabilities in the brain, from what I understand.
• a-dub 4y ago
  forensic image analysis is cool and all, but i think maybe instead of: "A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the disease." it would be better to see: "A neuroscientist conducts an irrefutably strong study that upends 16 years of theory on the disease process behind Alzheimer's." i don't care if someone cheated, i care that their results are discredited by scientific processes, not forensic review.
  • appleflaxen 4y ago
    The scientific process is the systematic identification of what is true. Wikipedia: "the scientific method involves careful observation, applying rigorous skepticism about what is observed, given that cognitive assumptions can distort how one interprets the observation." So identifying fraud is the scientific process.
    • a-dub 4y ago
      sure. but i think i'd rather see biologists debunk prevailing theories in biology by doing biology while in the process getting better at biology rather than dabbling in forensic image analysis. (although, who knows, maybe said dabbling could lead to some new meaningful insights down the line) i guess the bigger point is that the act of topical inquiry should have inbuilt mechanisms for discarding ideas and approaches that turn out to be dead ends, without having to rely on them actually being fraudulent (they can be, and often are, completely legitimate, yet also completely wrong). we shouldn't be discovering bad ideas in science by fraud detection, we should be discovering them by mainstream scientific process.
• 1-6 4y ago
  How does this finding affect companies that have created therapeutics related to Beta Amyloid such as Eli Lilly or Biogen?
  • rmatt2000 4y ago
    I wonder if the Univ. of Minnesota is has any potential liability here?
• narrator 4y ago
  Methylene Blue is in phase 3 trials with Taurx[1] The patented version will be slightly tweaked version of the century old drug so they can make some money on it. Still, it would be one for the ages that an out of patent cheap drug makes decades and billions of research obsolete. They say it clears tau, but it probably works some other way like being an antimicrobial that can cross the blood brain barrier. A doctor I know takes Kordon methylene blue which is pennies a dose. [1]https://taurx.com/the-science/clinical-trials https://taurx.com/the-science/clinical-trials
  • pengaru 4y ago
    > A Phase 3 clinical trial of LMTM (TauRx0237 or LMT-X), a derivative of methylene blue, failed to show any benefit against cognitive or functional decline in people with mild to moderate Alzheimer's disease. Disease progression for both the drug and the placebo were practically identical. https://en.wikipedia.org/wiki/Methylene_blue#Alzheimer's https://en.wikipedia.org/wiki/Methylene_blue#Alzheimer's
    • narrator 4y ago
      The cite for that was from 2016. The latest study has yet to publish results. https://clinicaltrials.gov/ct2/show/NCT03446001?term=TRX0237 https://clinicaltrials.gov/ct2/show/NCT03446001?term=TRX0237
      • pengaru 4y ago
        You act as if the cited article was simply about an honest presentation of negative results. When in fact it illustrates a similar kind of dishonesty and manipulation as TFA being discussed in this thread. I don't see why we should have any amount of optimism in this direction based on the evidence in front of us. Do you hold stock in TauRx or its affiliates? https://www.alzforum.org/news/conference-coverage/first-phase-3-trial-tau-drug-lmtm-did-not-work-period https://www.alzforum.org/news/conference-coverage/first-phas...
        • 4y ago
• de6u99er 4y ago
  >Journals are often uninterested in negative results, and researchers can be reluctant to contradict a famous investigator.
• hcknwscommenter 4y ago
  Something doesn't quite make sense here. It seems there is good evidence that certain figures in Lesne's papers are fraudulent. Certainly that is a huge red flag and it is likely that some (or all) of the findings are wrong. But that doesn't mean that the paper's ultimate conclusions are necessarily incorrect. I mean, thousands of papers go on to report on Aβ56, do they all just assume that Lesne's findings are true without further investigation? That seems highly unlikely. What's notable is that the entire article here never once refutes the most important finding of the original Lesne paper (Aβ56 can produce alzheimer's like symptoms in rats).
  • appleflaxen 4y ago
    > What's notable is that the entire article here never once refutes the most important finding of the original Lesne paper (Aβ56 can produce alzheimer's like symptoms in rats). You refute a paper by showing that part of it is incorrect. The research sleuths have provided incredibly strong evidence that the very existence of Aβ56 is demonstrated (in the paper) by a sham line on the western blot. It's like somebody has demonstrated that a photo of a "ghost" is actually a double-exposed film, and you are stating "What's notable is that the entire article here never once refutes the most important finding of the original photo (that ghosts can haunt the waffle house)."
• fithisux 4y ago
  Covid jabs are the next frontier in fabrication.
• ken47 4y ago
  Within its statistical boundaries, the scientific method is absolutely trustworthy. Humans though? Not so much.
• WhitneyLand 4y ago
  “The immediate, obvious damage is wasted NIH funding and wasted thinking in the field because people are using these results as a starting point for their own experiments,” says Stanford University neuroscientist Thomas Südhof, a Nobel laureate and expert on Alzheimer’s and related conditions.” I guess he’s the Nobel prize winner, but I would’ve thought the immediate and obvious damage was unnecessarily delayed research progress while people are dying. Over a decade? Who knows what the overall impact was.
• icermann 4y ago
  I think many of us has heard about the Xerox copying machine changing digits on copies, using a "visually similar enough" replacement algorithm. https://www.theverge.com/2013/8/6/4594482/xerox-copiers-randomly-replacing-numbers-in-documents https://www.theverge.com/2013/8/6/4594482/xerox-copiers-rand... I wonder if you could get the same unexpected result when copying images of Western blots? It's probably not the case here but it could be devastating for a researcher to be accused of fabricating data by using an affected copier/image editor/file format.
  • appleflaxen 4y ago
    No. The xerox machine had a digital analysis phase with a feedback loop between the image being recorded and the output being printed. A western blot is a direct measurement. It's like asking whether the xerox example might explain why the splatter pattern is identical in sections of two putatively different Jackson Pollock paintings.
    • icermann 4y ago
      Maybe I didn't make myself clear, but the image in the article looks like it could have made both one and two passes through a Xerox machine before it ended up in the paper.
• bluenose69 4y ago
  A new wrinkle in all of this is the current practice of promoting research to the public. Many (most? practically all?) universities employ nontechnical people whose jobs it is to identify newsworthy research results that can be dumbed-down and puffed-up in press releases. Granting agencies do the same thing, either directly via newsletters and press releases, or indirectly, by encouraging research teams to hire public-relations people. Members of the public cannot be expected to be able to read, let alone understand, the dizzying array of specialized articles that are published on any given topic. Heck, this is a real challenge even for scientists looking at work that is slightly outside their domain of expertise. Some form of overview is necessary, but press releases, usually biased and ill-informed, are just not the way forward. But will press releases go away? No chance. This is how students get attracted to universities, and it's how alumni get encouraged to donate for that oh-so-important sports complex.
• Gatsky 4y ago
  > She and others in the lab often ran experiments and produced Western blots, Larson says, but in their papers together, Lesné prepared all the images for publication. This is a well known thing scientific fraudsters do, “touche finale”. Any scientist knows preparing figures for publication is tedious, no PI in their right mind would routinely do that.
• dav_Oz 4y ago
  One needs a theory of mechanism to develop an intervention i.e. "new drug". The simpler the better. But given the tremendous complexities involved in biological systems one has to be very careful with the data. Quite frankly most in the field are not sufficiently trained or aren't rigorous enough in dealing with uncertainties and I wouldn't blame them it's mind-boggling and paralysing. This of course can be exploited given the incentives stated above combined with the public's unawareness of e.g. statistical significance vs clinical significance etc., with the myriad mathematically correct ways of presenting data, and a handwaving attitude about reproducibility, this really opens up the floodgates for someone in a lab to become "creative", an entrepreneur. Which of course should be highly discouraged in the context of scientific research and in order to relieve some pressure the community once in a while condemn the most daring of examples without imhv looking too deep into the entrenched mechanisms enabling this. A PhD student (biomedicine) once jokingly told me about the old HeLa contamination "problem"[0] in labs experimenting with cells. I must have reacted shocked as he laughingly added: Well, that was quite a long time ago, the problems now, only compounded. So, in order to get the full picture it is "healthy" to zoom out and look at the other side of the spectrum i.e. longitudinal studies (with its own sets of limitations). One impressive one relating to Alzheimer's is the famous nun study[1]. [0]https://en.m.wikipedia.org/wiki/HeLa#Contamination https://en.m.wikipedia.org/wiki/HeLa#Contamination [1]https://en.m.wikipedia.org/wiki/Nun_Study https://en.m.wikipedia.org/wiki/Nun_Study
• kazinator 4y ago
  These dots don't connect for me very well in this article: > In 2006, Schrag’s first publication examined how feeding a high-cholesterol diet to rabbits seemed to increase Aβ plaques and iron deposits in one part of their brains. Not long afterward, when he was an M.D.-Ph.D. student at Loma Linda University, another research group found support for a link between Alzheimer’s and iron metabolism. Yet, fast forward to December 2021 or early 2022: > Three of the papers listed Lesné, whom Schrag had never heard of, as first or senior author. If Schrag was doing research in the same area, at around the time Lesné's results started to dominate, propelling his career, it's odd that Lesné's existence somehow eluded Schrag for 16 years. Did Schrag switch to something else at around that time and never give it a second thought for a decade and a half?
• Nelkins 4y ago
  I think we are going to find out that diet plays an enormous role in all sorts of metabolic diseases in the coming years. Specifically as it pertains to Alzheimer's, increasingly strong evidence is coming out that your risk can be reduced by avoiding excess carbs/glucose, and also by avoiding oxidized foods (in the typical Western diet, usually polyunsaturated fats that have been sitting in a bottle). Presentations like these are very compelling: https://www.youtube.com/watch?v=O36CNNdgDGQ https://www.youtube.com/watch?v=O36CNNdgDGQ https://www.youtube.com/watch?v=-tiGIIGOQS0 https://www.youtube.com/watch?v=-tiGIIGOQS0
• sfrautschy 4y ago
  This is ridiculous. Dozens if not hundreds researchers have confirmed the high MW oligomers correlated with pathogenesis. I have. To say that he found this or everything relied on this theory is absurd. We've know this since the early 90's when Lesne was in high school or earlier (e.g Cotman's work at UC IRVINE and Christian Pike now at USC , my work etc.) . this is way before Lesne even considered a career. I can't stand this ridiculous media that make this out a scandal and create false disinformation that the entire hypothesis is based on this.
• sfrautschy 4y ago
  This is ridiculous. Dozens if not hundreds researchers have confirmed the high MW oligomers correlated with pathogenesis. I have. To say that he found this or everything relied on this theory is absurd. We've know this since the early 90's when Lesne was in high school or earlier (e.g Glabe and Cotman's work at UC IRVINE and Christian Pike now at USC , my work etc.) . this is way before Lesne even considered a career. It used to be called "micelles' or soluble abeta. Also the post doc supervisor repeated the data and found the same thing so she took him at his word. I can't stand this ridiculous media that make this out a scandal and create false disinformation that the entire hypothesis is based on this.
• atombender 4y ago
  I recommend reading the comments on AlzForum [1]. From the discussions (which are from real Alzheimer's researchers), 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, and not significant to the field as a whole. [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...
  • panabee 4y ago
    thanks for sharing this. it would be ideal if these comments could get integrated into the original article. it's interesting that ashe commented here and not when contacted by the journalist. hopefully this fraud didn't truly cause unnecessary delays in pursuit of a cure.