Researchers to retract landmark Alzheimer's paper containing doctored images
science.org
science.org
So around 18 years ago. That’s a long time for researchers that believed in this papar's conclusions to be going down the wrong rabbit hole. What a huge waste of effort and the lives of those with Alzheimer's.
This is in addition to wasting a big chunk of the billions spent each year on Alzheimer's research on false leads (see https://www.alz.org/news/2024/congress-bipartisan-funding-al... for a source on the billions).
Yes, very serious consequences indeed. (Note, I did my best to back up my statements with high quality unbiased factual references. Please read them before disagreeing with my description of the result.)
Preregistration might help, but it doesn't really address the misaligned incentives that are at the heart of academic fraud.
I have been asked to manipulate data a few times in my career. I have always refused, but this came at the cost of internal fights, getting excluded from other projects for being "too idealistic", or missed promotions. Incentives are just perverse. Fraud and dishonesty are rewarded, pretty depressing.
Everyone wants answers, so anyone that provides an answer is elevated, independent of if the answer is right or not. To wit: the current AI push.
Clips from The Big Short surfaced in my YouTube feed recently, and they way you worded this reminded me of the scene with the rating agency.
Is scientific research and publishing headed for it's own CDS/MBS-esque implosion?
But, for completeness, paper retractions can happen for many reasons, not all of them nefarious, though it could be that most retractions are from authors trying to game the system and getting called out. For example, if the terms of using a certain data set change, you could be required to retract your paper and remove that data from the analysis.
This of course is pure speculation
It does lend to an interesting thought experiment, though.
Imagine the researchers were right after all. They just needed more time, and so they faked some results. We might have ended up with an underdog/feel-good movie about how the researchers bravely persevered in spite of the drying up of their funding.
https://scholar.google.com/scholar?cites=1621513420842042156...
But one should not exaggerate the impact it had. The strongest support for the amyloid hypothesis of Alzheimer's comes from multiple sources of evidence that are completely unrelated to this paper.
What we do know is that finding academic fraud is like shooting fish in a barrel. It's way too easy even for totally unfunded volunteers. The situation in science right now is reminiscent of the situation in computer security circa 1999. Back then there were so many easily exploited RCE vulns in foundational infrastructure that "hacked by teenagers" became a TV trope. Almost anyone could sit down and find a way to hack into a network without much effort. Vendors engaged in a lot of screaming and denial, sometimes even attacking the people who found exploits for them.
But, the industry changed. White hats became widespread, companies hired those ex-teenage hackers in their thousands. They put every employee through trainings. Then when that wasn't enough they started paying out millions in bug bounties, buying sandboxing companies (like Google did for Chrome) and more. Companies did this because bad security was hurting their reputations and in a competitive market that is an exploitable weakness. It was a form of self defense.
Academic science is excluded from market mechanisms by legal fiat, supposedly on the basis that this will yield better research outcomes. What it's actually done is shield universities from any need to make hard changes. Their reputation is tanking but they just don't seem to care and why should they? They'll get grants from the NIH anyway because they're all as bad as each other, and nobody in politics is talking about a total defunding of the sector yet.
Unfortunately even if the grants were cut off tomorrow they probably would still find it hard to change. It's becoming apparent that if a culture tolerates fraud for decades then eventually the leadership of these institutions are people who got there through fraud. How are universities or journals going to reform when the people who run them know full well they can't crack down on fraud without exposing their own career to audit risk?
'Market mechanisms' already exist - no company is precluded from doing research. We can discuss the deficit in research investment that short termist 'market mechanisms' have led to in contemporary corporations, but its absurd to claim that the market can or should replace academic research.
It's pretty clear that in practice the 'publish or perish' academic culture fostered by the financialisation of the university, the rise of the adjunct and the death of tenure have contributed heavily to the falsification of research. In practice encouraging replication, self directed research and significantly more 'pure' 'blue sky' research than governments and universities are inclined to do, would significantly alleviate this problem.
Academia needs far less exposure to 'market mechanisms'. They're perverse incentives for good science.
If anything research is clearly over-funded right now, especially in some fields like medical research. That's why so many scientists turn to fraud in desperation. There just aren't enough genuine discoveries to go round.
> encouraging replication, self directed research and significantly more 'pure' 'blue sky' research
Replication is the opposite of self directed blue sky research, so how do you suggest it be encouraged whilst simultaneously reducing the power of the money givers even further? BTW, many bogus papers will replicate whilst still being wrong. Replicability is not a synonym for good science.
Really, this is a very common claim that needs to go away. The solution to fraud and incompetence is not to give incompetent fraudsters even more freedom and money.
Markets don't discover "the right" (i.e. social welfare maximizing) resource allocation, they discover, under ideal conditions, a pareto-optimal allocation. This is a very weak condition: "Jeff Bezos owns everything" is pareto-optimal. You need redistribution if you want to turn that into a socially optimal one.
In realistic conditions, they don't even do that: market mechanisms will reliably underinvest in things with positive externalities, and the larger the externality the greater the degree of misallocation. The positive externalities of research are enormous compared to the value captured by the researchers.
> The positive externalities of research
... are only relevant if it's actually research, and not something that looks a lot like research without actually being so.
And a world class propaganda game. Go onto mainstream social media, pick a science fan at random out of the crowd and pick an argument with them about science. The average fan would have you believe that science is just short of perfect.
In a sense it's hard to blame these people, considering what two years of the media machine's full court press of pro-science culture war propaganda during a global pandemic does to a mind of average intelligence.
I mean, I suppose "winning" is important folks, but is losing your soul in the process worth it?
This to me just seems untrue. What is your basis for this claim? There is plenty of research privately funded by corporations, some of which is very influential. Often this work is published by university researchers. Ask any university researcher about the numerous compliance courses we all have to take about funding and conflict of interest.
It is true that the biggest funders (NSF, NIH) are not market-focused, but for good reason. The market does not prioritize the public good. I know first hand -- my son has a rare disease (1 out of 20,000 people). There are many drug companies putting vast resources into drug development in the hopes of a huge payoff. In reality this benefits a small number of people (I remain grateful for how improvements have helped us). I'm grateful our major scientific funding bodies are not swayed entirely by market influences because it would lead to us focusing on a narrow set of scientific problems which would ultimately limit the way it helps the public good.
Im any event, I work in biomedical research. I think your diagnosis (incentives, process) is correct, but the way you discuss the attitudes and motives of researchers is wrong-headed.
You say:
> Their reputation is tanking but they just don't seem to care and why should they? They'll get grants from the NIH anyway because they're all as bad as each other, and nobody in politics is talking about a total defunding of the sector yet.
You're talking about hundreds of thousands of researchers as if they're all psychotic citation fanatics with no care for truth. That is not reality. I think the kind of psychotic, data-manipulating researcher who would put people's health and lives at risk for citations -- or fabricate data sets out of thin air -- are vanishingly small. We can point to a handful of them -- the author of this paper, and the Daniel Ariely's and Francesca Gino's of the world -- but there are tens of thousands of people in every field working on research in good faith, with utmost care. The vast, vast majority never have any scandal, never get caught up in data manipulation, and so on.
No field I know of out-right tolerates fraud (and I follow all the retraction stories fairly closely). I think the closest we get to "toleration" is researchers dealing with scientific problems who more or less say "we're not going to publicly flay you but behind your back we're all going to know what you did and your future is limited when it comes to big grants, prestigious invitations, and so on." People who are credibly accused of fraud become pariahs and often targets of scorn not only within the research community but in the press and wider community.
The most serious issue IMO is not outright but poor norms around scientific practice, leading to p-hacking, harking, and other "forking paths" problems. Calling that type of behavior "fraudulent" is perhaps justifiable under some ways of thinking, but I think the word fraud mischaracterizes what is going on. There are, in fact, many serious efforts to root out this type of behavior and put in transparency rules to open up research to scrutiny, including among funders like the NIH.
Well you answered your own question: It is true that the biggest funders (NSF, NIH) are not market-focused. A lot of research is funded by taxes. That's an exclusion from market mechanisms. They don't have to convince the actual consumers of the research to buy it, we are all collectively forced to buy it by law.
> No field I know of out-right tolerates fraud
I know quite a few such fields, so we might have a different definition of "tolerate". After all this story contains the following paragraph:
“It’s unfortunate that it has taken 2 years to make the decision to retract,” says Donna Wilcock, an Indiana University neuroscientist and editor of the journal Alzheimer’s & Dementia. “The evidence of manipulation was overwhelming.”
We're talking about a retraction here, which is the weakest response possible. So ... it took two years of "investigation" to do nearly nothing, after other people did all the investigative work for free, and one of the authors continues to be employed with no consequences whatsoever even though his co-author admitted the figures were tampered with. I'd argue this is what institutional tolerance of fraud looks like.
You're talking about fundamental research into basic scientific questions as if it were the same as potato-chip manufacturing.
As for commercial research, similar problems of fraud exist as in academic research. Instead of prestige, the motivations are things like bonuses and promotions.
Academics actually care a great deal about fraud, funding agencies hate fraud and punish it, journals hate fraud - everyone dislikes it. Competing labs have every incentive to catch fraud conducted by their rivals. The idea that academia is rife with fraud and that nobody cares is just not true.
There will always be a certain level of fraud not just in research, but in every economic sector, every intellectual pursuit, and every sport, commercial or not. There's no system that will perfectly eliminate it, but because of its empiricism and openness, science is fairly good at correcting itself over time.
The same problems exist but not on the same scale. If your employer discovers you committed fraud to get a promotion you will certainly be fired and quite probably be taken to court by their legal department. If the fraud is at the level of the company they risk destruction and imprisonment by the government. It's not like in academia where they'll sit on it for years and then, maybe, request a little notice to be put on the paper's web page - all without the government even noticing let alone caring. The huge difference in consequences yields different risk/reward ratios and that's reflected in how often these problems are found.
> Academics actually care a great deal about fraud, funding agencies hate fraud and punish it, journals hate fraud - everyone dislikes it.
Do they? How is the co-author of this paper still employed if funding agencies punish it? Where are the university funded research-police departments? Why do we keep hearing cases like this Alzheimer's one and why are there never any announcements by Vice Chancellors about doubling investment into fraud investigations as a consequence? Why is a research audit not something that these fraudsters fear? How is it the case that publishers discover after the fact that dozens of their journals have been completely compromised by paper mills, instead of it being discovered via some more active process before publication occurs?
> science is fairly good at correcting itself over time
Absolutely not. If science was good at self correcting it wouldn't take nearly two decades for someone to notice that a widely cited paper was forged, and the people who notice these things wouldn't need to be anonymous. But they do. Look at the Gino case. She launched a massively well funded lawsuit against the people claiming she engaged in fraud. That's the exact opposite of self correction.
Almost all funding for basic research, including for physics, comes from governments. There are a few niche areas of basic research, like quantum computing, that also attract commercial investment, and there is plenty of applied research, but governments are almost the only game in town for basic research.
I think fraud is actually a much larger problem in commercial research, because the incentives to cheat are much stronger. There's real money at play. Theranos was a massive fraud. There's plenty of fraud and misconduct in the pharma industry. And when it comes to academia, the fields that have the most commercial potential (like biomedical research) have the worst problems with fraud.
> How is the co-author of this paper still employed if funding agencies punish it?
Is the co-author guilty of fraud?
> Where are the university funded research-police departments?
It's the funding agencies, the journals and other academics that are most involved in finding fraud.
> Why do we keep hearing cases like this Alzheimer's one
Because there's a huge volume of research, and some small percentage of it will be fraudulent.
> why are there never any announcements by Vice Chancellors about doubling investment into fraud investigations as a consequence?
That might be a bad allocation of resources. If fraud is a rare phenomenon and isn't severely impacting a field, then the current level of investigations might be sufficient. Add to that the fact that the way most of these frauds are uncovered is by competing researchers.
1. Grants and faculty positions should be less dependent on number of publications, and more on the quality of publications.
2. Place more emphasis on basic research and less on translational research. The latter encourages hyperbole and p-hacking. In the late 90s, the NIH initiated a strong emphasis that all research should have an immediate practical value. This is not reasonable and as a result, researchers grossly exaggerate the impact of their work, and some even engage in an outright fraud.
- How many times has the results been reproduced by others? - Add another layer of blindness: the person doing the lab work is not the person crunching the results. It could even be where two different groups crunch the numbers, and all groups are unknown to the others. - Avoid p hacking with pre determined (and registered!) p values - Register the experiment with hypothesis before the start of the experiment - Register authors as they are added and removed, and have that history be publicly available - All results have to be uploaded to a website before publication - The method of calculation has to be public on a website before publication.
So a high quality paper is one where - the experiment was logged in advance - the history of authors is known - there is a distinct separation of experimenter and cruncher - the public can get the results themselves and run the same analysis to confirm (or not!) the results - the experiment is repeated and confirmed by others. Even if the first experiment is bad or a fraud, and the second one doesn’t confirm it, a third experiment could be the tie breaker. It would be more traceable to understand if it was the lab or the cruncher that made a mistake or was committing fraud.
Overall, we have to incentivize good science.
1. Pre-registration. Great idea, it's often being done. Doesn't work because universities don't enforce it. They'd have to proactively check that papers match their pre-registrations and then fire people when they don't.
2. Reproducibility. Nobody gets funded to do this but even if they did, there are lots of bogus studies that can easily be reproduced. The problems are in the methods rather than the data. If you specify a logically invalid or unscientific method, then people following your instructions will calculate the same results and still be wrong.
3. Blindness/splitting work up. This is already how many papers are made and academics turn it around as a defense. Notice how in every single case where this stuff happens, the people whose names are on the paper claim the fraud was done by someone else and they had no idea. Universities invariably accept this claim without question.
4. All results have to be uploaded before publication. Did you mean raw data? Results are the primary content of the paper, so it's unclear what this would mean. Researchers in some fields heavily resist publishing raw data for various (bad) reasons, like academic culture rewarding papers but not data collection efforts, so they're incentivized to squeeze as many papers out of a dataset as possible before revealing it to competitors. In a few fields (like climatology) they often refuse to publish raw data because they're afraid of empowering people who might check their papers for errors, who they see as a sort of shadowy enemy.
5. Authorship history. Which frauds are you thinking of that this would fix?
I spent a lot of lockdown time looking at this question. You've listed five ideas, I churned through maybe 15-20. None of them work. On investigation they've usually been tried before and academics immediately work around them. Science is littered with integrity theatre in which systems are put in place in response to some fraud, and they appear to be operating on the surface, but nothing is actually being checked or enforced.
> Overall, we have to incentivize good science.
I'm by now 95% convinced the only way to do this is for scientific research to be done commercially. No government or charitable funding of science at all. As long as science is being firehosed with money by people who don't actually use or consume the resulting papers, the incentive will always be to provide the appearance of doing science without actually doing it. It's just so much more effective for fundraising. Commercial science that's purchased by someone has a customer who will actually try to check they got what they paid for at some point, and can vote with their wallet if they didn't. Also legal protections and systems to stop fraud in markets are well developed. Notice that Elizabeth Holmes went to prison for defrauding investors. If she'd done the same thing at a university she'd have gotten away with it scot free.
But she didn't though. She was rejected from academia, which is why she turned to private capital. Her fraud worked on private investors, not government funding agencies. She couldn't even convince her professor to get behind her idea, but private funds threw millions of dollars at her.
That on the clean part. I've also seen papers published well above its merit just because the authors know the editors, or the paper comes from a reputable lab so it must be good. Also, the opposite is true: your work is from a small or unknown lab, or goes against the grain, and you'll be lucky if you get published at all.
Certainly not by citations counts. Citations have more to do with the authors social or scientific network than the worth of the papers.
> It was cited three times in the following 35 years. By all metrics, it was a low quality work.
It was not low quality work (although it did spark quite a bit of controversy due to its perceived or actual issues). It was just an article written by an unknown author in an unknown journal.
Unfortunately, many papers that come from obscure labs and go against the grain are both bad and wrong. It's a hard problem.
Like open a betting market for study replication. If no methodological errors are found and the study can be successfully replicated the authors get a percentage of the pool, replication effort is run by a red team that gets paid the same percentage of the pool regardless of outcome making their incentive to find bets that just attract a lot of bets.
This would incentivize scrutinizing big findings like the one in the OP where a failure would be big, but also act as a force for unearthing dark horse findings in journals off the beaten path where replication success would be big.
In the balance between trying to quickly develop a therapeutic and understanding the basic mechanisms driving the disease etiology, we see a lot of research groups with under powered studies playing fast and loose and hyping their research. Is it outright fraud? Rarely. But it’s not good science either.
The commercialization of academia rewards churn and volume rather than $upporting (a semi-orthogonal constraint) and promoting landmark hard-work that takes longer to gather data or develop.
Perhaps data-oriented research needs to consider extraordinary rigor as the new normal, perhaps with internal and external audits to assure standards and practices are sound.
https://x.com/MicrobiomDigest/status/902016709019672577
These efforts are just going to accelerate with AI applied, new and exciting frauds will be discovered.
[1] https://www.nature.com/articles/d41586-023-03974-8 (apologies of you don't have access to Nature)
Perhaps it was Ashe's Harvard education that led her to not consider double-checking the work...
Edit to add: iirc, it was the University of Minnesota that is also responsible for the "food fat is bad" advice that has made obesity than American epidemic...
The most surefire way to do this was to simply commit fraud rather than conduct experiments and pray you get lucky and find an outlier result worthy of significant rewards. We are witnessing the fallout now as people no longer assume honesty and integrity, and begin to analyze the actual papers for accuracy.
I asked him for advice on a problem in his field, and he basically couldn't answer. He talked about his degrees.
I think this person must have cheated. Its the only thing I can imagine.
Horrifying. 2 years investigating and they’ve commented on two images?
Universities cannot/will not investigate their own staff properly.
It should never be acceptable.
> Scientists are divided over whether the problems with the paper undermine the dominant, yet controversial, theory that beta-amyloid plaques are a root cause of Alzheimer’s disease.
How could it not at least be a wake up call that studies that use this paper as a base could be fundamentally flawed?
I get that it is complicated but fraud in one area (images) makes the hard data extremely suspect.
The real question (that I’m not sure about) is if anyone else has been able for replicate the original experiment.
As they say, it only takes one result to disprove a theory, but nobody has been able to do so to date.
https://www.science.org/content/article/potential-fabricatio...
Just look at the multiple plagiarism cases against the former Harvard president. It was clear, at least to me, she copied liberally more out of laziness/lack of confidence because she didn't think she would get caught for small phrases here and there. I mean, who goes through all of the trouble to write a dissertation and then plagiarizes the acknowledgements???
Ironically, the guy who led the charge against Gay, Bill Ackman, is married to a celebrity academic who committed real, bona fide plagiarism. Once that came out, Ackman suddenly had all sorts of excuses for his wife's actual misconduct, which makes it clear that he never actually cared about the issue of plagiarism. He just wants kids who protest against the war in Gaza to get expelled.
I don't necessarily agree with your overall characterization of Gay's plagiarism. While some of it is clearly of the kind you site (e.g. she's clearly referencing other work in a lot of her analysis, so the fact that she doesn't just reword some phrases a little more seems like a very minor transgression to me), there are other cases that are more than just sloppiness and are outright weird, like the acknowledgements issue. This opinion article from Ruth Marcus (a generally left-leaning writer) of the Washington Post highlighted the issues very well IMO: https://archive.vn/h8lqM
Ruth Marcus may be liberal, but she's also extremely pro-Israeli. The entire motivation for going after Claudine Gay was that she didn't stop students from protesting against Israel's war in Gaza, so Marcus' political stance on that issue likely colors her view on the plagiarism accusations.
Because it's pathetic? Again, this wasn't just one instance of sloppy plagiarism, this was a common thread throughout her extremely thin academic career. And Gay wasn't just some random undergrad, she was the president of what was supposed to be one of the most prestigious universities in the world! The plagiarism scandal was just more proof that Gay was woefully unqualified for her job.
The bottom line is that if Claudine Gay had cracked down hard on students for protesting against Israel's war in Gaza, she would never have faced these accusations, and she would still be president of the university.
I don't particularly care if she was a great president or not. I find it extremely unsettling that a few billionaires were able to oust the president of Harvard, as a way of forcing their own politics on the institution. Since her ousting, Harvard has moved hard against student protesters. Harvard got the message loud and clear, and that message had nothing to do with plagiarism.
I expect somebody who reaches her level of achievement to adhere to the rules of academic plagiarism to the letter.
I am sure most citations are not by people who suspected the numbers were fudged.
If anything, the way to go is to stop using flawed metrics. Most people want to do a good job and build a good reputation. Incentives just distort this.
With LLMs we can read all the papers at once and flag the most strongly derived for further review.
> I could be wrong about this, but from this vantage point the original Lesné paper and its numerous follow-ups have largely just given people in the field something to point at when asked about the evidence for amyloid oligomers directly affecting memory. [...] The expressions in the literature about the failure to find *56 (as in the Selkoe lab’s papers) did not de-validate the general idea for anyone - indeed, Selkoe’s lab has been working on amyloid oligomers the whole time and continues to do so.
[1] https://www.science.org/content/blog-post/faked-beta-amyloid...
I have, over time, come to treat every paper I read as being based on lies and fakery (or incompetence, unconscious bias, or intentional omission of key details), and I work to convince myself that the paper is not fradulent or false. That is, my null hypothesis is that published work is wrong.
After chattiing with many people about this, I've found that most people default ot believing a paper is right and if the figures and conclusion agree with their bias, they just move on, beliving the paper to be true. I've been guilty of this in the past as well.
This paper being manipulated doesn't imply anything about the hypothesis or any subsequent studies - it simply fails to be useful as any form of evidence.
Drama drama drama, feed the people more drama... sigh
Because that was covered in detail when the manipulations were first reported and those articles are linked to in the above article. This is just reporting on the resulting retraction two years after that initial report.
>it's much less dramatic and all the findings were also replicated following this inquiry to show that any image alteration, that might have been made for editorial purposes, does not affect conclusions
Other groups had issues replicating the results with the same oligomer (often just chalked up to its instability), it's not like someone just happened to stumble upon these manipulations casually. This retraction only happened because Nature rejected the author's attempt to publish a correction. This whole thing is a black mark on Nature's record as well so if it really was just some minor change to make a picture look prettier for publishing purposes, I doubt they would have insisted on this action
I suspect alzheimers (which is a subset of dementia), is a cluster of diseases similar to cancer. I think a large subset is due to candida, but I wouldn't be surprised if mold and other environmental toxins cause other subsets.
On one hand, these people have a big responsibility to do good work and stay out of trouble for the sake of the ones they're helping (i.e. Alzheimer's patients), but on the other hand their impact depends a lot on their mental/emotional state -- if you put more bs in their mental buffer, it's naturally going to mess with them and lead to a decline in quality. They have to focus.
Distrust in science is at an all time high and these frauds cause incalculable damage to scientific integrity. They are literally poisoning the well of human knowledge. That should be considered a high crime.
This amyloid theory has been completely debunked at this point but has wasted almost two decades of progress because of it. It's so infuriating, but I don't see this stopping because there's no accountability.
This claim is just an opinion. I bet that if we check the real statistics there are lots of cases that show exactly the opposite behavior.
> making money and winning awards is the goal
We should remind that making money and winning awards are perfectly legit goals, as long as the work is done honestly.
Working with Alzheimer patients rank probably among some of the most emotionally hardest and more depressive works that I could imagine. We should stop treating scientists as missionary figures that were born to save all of us for free.
If it was just a big cartel conspiracy, you would see a different disease pattern when comparing the elites to everyone else.
Of note: Cancer and Alzheimer’s disease inverse relationship: an age-associated diverging derailment of shared pathways Molecular Psychiatry vol. 26, pp. 280–295 (2021)
People needs to stop making excuses to avoid science, use their brain cells and grow some critic sense. When you feel afraid of science, stop and think that the other option is worse.