I recommend reading the comments on AlzForum [1]. From the discussions, it sounds like this fraud is significant in terms of Dr. Sylvain Lesné's work, but that the news has been vastly blown out of proportion.
These comments are written by real Alzheimer's researchers. They all disagree with the notion that Lesné's papers have been important to the field, and therefore undermine the idea that this has any bearing on "two decades of Alzheimer's research". (Karen Ashe, co-author of the main paper referenced here, also stops by the thread.)
I agree, the discussion here is reassuring. This may just be a case of a fraudulent paper piggybacking on an otherwise credible research program focusing on amyloid oligomers - not the plaques which recent failed therapies have targeted, and which many of these researchers knew were poor targets for decades before the FDA debacle over aducanumab.
We can blame regulatory capture of the FDA for approval of failed drugs, rather than the scientific establishment. And we can blame Sylvain Lesné for Sylvain Lesné's fraud.
I would encourage those of us whose only knowledge of this topic is the word "amyloid" (I admit I am one of them) to read the scientists' comments and appreciate that there is more to this than we know. There are complexities, nuances, diverse perspectives and healthy disagreements. It's not just a political battlefield. Projecting culture war into it would be harmful to the scientific progress we all value and to the millions who suffer from Alzheimer's.
Why, at this point should we believe any one scientist writing in that forum wasn't already sunk far deep into amyloid research in their career?
Not to mention that after a quick glance on the comments section, I fail to see where you get the idea that "They all disagree with the notion that Lesné's papers have been important to the field". Apart from the very first comment from karen Ashe (who will obviously be defending her research) and a few other who's working on related topics, other commenters seems to be keeping their suspicion at amyloid hypothesis.
Can we replace the link with the original Daily Kos article [1] that this is a copy-paste of? I have no idea what wallstreetpro.com is, but it looks like blog spam.
The bit at the end about the NIH continuing to allocate funds to the exposed researchers... with the program director being one of the authors of the exposed paper - that stings. But it also shows how deep corruption and "networking" runs in places like this.
Academia and research needs a new broom. Presently incentives are
peverse. Impact factors, publisher corruption, grant applications and
funding are a blight on science.
This is very similar to another scientific fraud case from two decades ago, involving Bell Labs and Jan Hendrik Schön, and a series of major papers published in Nature and Science from 1998-2002, and described in an excellent book, Plastic Fantastic: How the Biggest Fraud in Physics Shook the Scientific World by Eugenie Samuel Reich.
A key point, from the above review, that I think explains a lot of this behavior:
> "Reich points out that fraudsters like Schön could get credit for “first discovery” if, before they are caught, their false claims are confirmed by others on the basis of genuine data."
It did shake up the field of organic semiconductor device research in physics by increasing scrutiny and changing some requirements (for example, electron microscope imagery of claimed devices is now a requirement for publication). However, as the top post at present notes, the incentives are backwards in academic science these days, and the role of funding organizations and high-profile journals is as problematic as that of the originating fraudsters.
Maybe this instance of fraud will do the same for the biomedical field, by forcing researchers to release their raw data and full-resolution images as a condition of publication, although that would require a major shift in behavior in today's patent-driven startup-centered heavily-corporatized biomedical research world.
Personally, I'll note that during the years I worked in academia, of the three PIs I worked with, I discovered two engaging in fraudulent research to greater or lesser extent. The main differences between them and the one who wasn't were (1) lab notebook discipline and recording and storing data securely, (2) in-house replication was required, (3) no toleration for BS and shady behavior. The others broke all those rules. (Unfortunately I picked the wrong PI to work with, and ended up leaving academia in a fit of contemptuous disgust.)
A good rule of thumb: If some research claim hasn't been replicated, and if the data and methods aren't transparently available, then it's as likely to be fraudulent garbage as not, and it's not worthy of further examination.
If what is presented in this article is actually true that would be a systemic failure of epic proportions, right? Not just in this concrete case but don't these fundamental papers get reproduced before everybody takes them for granted and pours in enormous amounts of research grants believing in them? Is this article an exaggeration?
I'd like to know whether the police have ever been brought in for a scenario like this. It may not seem as clear cut as regular financial fraud, but the end goal is to further one's career, which results in monetary gain. As such, this does seem to fall within most countries' definition of fraud. For example, from the UK:
In this conversation, it’s important to distinguish science itself (which, along with facts, are already under attack in our politics) from failings of the research industry.
Most interesting to me, is how if you get the model wrong, thousands of scientists will use it anyway, billions will be spent, but no one challenges it! Amazing.
It really lays open how easy it is to mislead everyone. All these siloed scientists won't have a clue anything is wrong. This is how conspiracies would work... if there is advantage to someone somewhere and they have the means to alter the model in their favour, why wouldn't they?
The linked article is sensationalized an disingenuously mixes the author's opinion with straight reporting on the Science article[0] previously discussed here[1]. Science never suggests that anybody other than Lesné was involved in falsifying results, and even then it is careful to not accuse him of deliberate fraud. Neither article suggests who the second scientist referenced in the headline may be.
I suspect there was deliberate fraud, but this article doesn't provide any more evidence of that than previous articles.
> Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. Meaning that patients who did die from Alzheimer’s may have been misdiagnosed as having something else. Those whose dementia came from other causes may have falsely been dragged under the Alzheimer’s umbrella.
I think the author is confused about the controversy he is reporting on. Nobody is suggesting that there aren't elevated levels of Aβ in Alzheimer's brains. The controversy is only about the presence of Aβ56, and as far as I know Aβ56 was never used to diagnose Alzheimer's disease. It should also be noted that this is only relevant to postmortem diagnosis, so even if they were testing for Aβ*56 it wouldn't have affected the diagnosis of living patients.
At the bottom of the article is a note, "Article written by Mark Sumner via Daily Kos". This explains a lot. Daily Kos is a site that got its start with sensationalized political articles. Now they've apparently expanded to subjects where they can do more damage.
---
As I post the comment, the title of the linked article is: "Two decades of Alzheimer’s research was based on deliberate fraud by 2 scientists that has cost billions of dollars and millions of lives"
The most likely motive for this kind of fraud at this level is that the researchers “know” their hypothesis is correct and are just fixing some “mistakes” in the data.
People do this all the time. In fact I’d say it’s the usual reaction when confronted with data contradicting one’s beliefs.
Scientists are supposed to learn to go past that but I wonder how many actually do, especially when there is both social and economic pressure to conform to a school of thought.
By far the most effective preventer of dementia appears to be vaccinations, with 40% effect size. It doesn't seem to matter what against. Second might be antivirals against herpes.
These people need to be formally immediately banned from any NIH activity, and criminally charged. We have known for years that their crap work was useless.
„I sincerely doubt that the absence of this particular paper and AB*56 from historical scientific record would have significantly changed the last 20 years of AD drug development. That is because there is strong genetic and other evidence for the role of amyloid in disease.“
That thread appears to be defending what appears to be one of the deadest ends ever in medical research. How much failure do these people need? I'm genuinely curious.
Welcome to science folks. Having worked a decade around a campus regularly sitting in on presentations (and being in research myself) I can say I believe 80% of science wrong AND not reproducible, 10% being an outright fraud (10% being legit).
(1) As a researcher you lose funding m if you don’t produce
(2) funds aren’t allocated to reproduce
(3) Researchers who publish will block research that disagrees with their work (as they’re also reviewers) (will lose future funding / have more competition)
(4) Researchers wont rescind their work if later findings warrant it (no incentive to)
(5) N numbers are way too low (higher N is more money)
> I believe 80% of science wrong AND not reproducible
Maybe that's the case in your area of research. In mine (math, physics) it definitely isn't. So I would be a bit more careful about the wording here. ("80% of science" – what science?)
I don't have much to add, only that it's been my personal experience as well. Fraud and non-reproducibility used to be such ethereal concepts to me, issues that are discussed at a systemic level as an intellectual exercise.
But after becoming a scientist, coming across so many fraudulent papers, so much non-reproducible and poorly done research. And seeing how it's affected my own, the thing that's dearest to me, having to build on top of those results and work in that global environment. It's been heart breaking, I feel no love for science anymore.
There is no question that a very significant portion is wrong and some of it is fraud, but I feel like this is the wrong summary takeaway. Science isn’t the reason that science is messed up, people are the reason. All fields of human endeavor suffer from the same problems due to emotional and political and selfish people. It’s more like, welcome to humanity. Science is actually the best thing we’ve got, there is no alternative that has less BS and more truth. The 10% or so of science that’s right has transformed the earth in the last century.
I worry about framing this the right way, about the subtleties of how you say it, because there is currently a war being waged on public trust in science, and to some degree that anti-science war is being won. It’s potentially damaging to say “most of science is wrong” and just stop there. That’s a misleading framing in my opinion. In order to fix the funding problems, society as a whole needs to have trust in science, to believe that the majority of people doing science are politically impartial and also not wasting money or lining their own pockets, to believe that scientific progress is human progress.
It’s important to note that the incentive problems you cite mostly aren’t caused my any malicious intent. Disagreeing with someone else’s research, in my experience, isn’t often done with the primary goal of holding back good research, it’s done because the researchers actually disagree on the science, and the reviewer actually believes the proposed paper isn’t complete or correct or up to publication standards. Moreover, for science it’s very important for researchers to be critical of each other. That is part of why we need more replication study.
In biology and some parts of chemistry, I would say yes 80% of papers have a wrong conclusion (experiments are ok but not interpreted correctly) or completely wrong. But in other fields it is not the case. I'm pretty sure mathematics are much better. Physics it will depend on which branch some are closer to science-fiction anyway so are not verifiable, but most physics is good quality. It is hard to consider science as a whole because it is absolutely not an homogenous lump and practices in reviewing, publishing and peer pressure are radically different.
You get what you incentivize, and this is what we incentivize.
It’s probably about the worst in any field dominated by studies and statistics. Harder sciences are harder to fake as bad results can be more conclusively falsified.
I dunno, I feel like it’s bad but getting better. 20 years ago, nobody tried to replicate anything. Now it’s much more common and, I hope, expected for results like this one.
80% of science? How would things like GPS or rockets work if that was the case? What we consider reliable technology would be blowing up everywhere around us constantly.
I agree with everything on your list. Most of these problems are quite difficult to solve, but I think (2) is doable if we can convince politicians to unfreeze science spending that has been stagnant for decades. We need a new set of early career awards that require 50% of time/effort to be spent on reproduction studies.
100% agreed. I can't seem to get people to understand - most research studies find results that are not reproducible. Putting it nicely "Research has a reproducibility problem."
> (1) As a researcher you lose money if you don’t produce
This is the biggest problem in my view. My work in R&D taught me that
most of the time we don't produce anything. It's high risk. But it's
high in rewards, often in adjacent areas not primarily the focus of
the initial brief.
Surely all serious investors understand this. Research is something we
do for marginal returns. It's not an "innovation factory". With
things currently stacked against risk, research can only yield tepid
results.
Ad 5: more data doesn't help if the main problem of your research is that your data is shit. People benefit from generating tons of shity data because they get more money, which looks good on their resume. If their results are shit, they simply write "more data is needed" and they benefit even more from the call for more data.
First off science isn't a section of society, company, or group of people.
Second 80%? Your wild hyperbole has no value, makes no point, and reeks of immaturity
macintux|3 years ago
A month ago: https://news.ycombinator.com/item?id=31828509
dang|3 years ago
Potential fabrication in research threatens the amyloid theory of Alzheimer’s - https://news.ycombinator.com/item?id=32183302 - July 2022 (236 comments)
Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) - https://news.ycombinator.com/item?id=31828509 - June 2022 (307 comments)
How an Alzheimer’s ‘cabal’ thwarted progress toward a cure - https://news.ycombinator.com/item?id=21911225 - Dec 2019 (382 comments)
The amyloid hypothesis on trial - 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 - July 2018 (109 comments)
atombender|3 years ago
These comments are written by real Alzheimer's researchers. They all disagree with the notion that Lesné's papers have been important to the field, and therefore undermine the idea that this has any bearing on "two decades of Alzheimer's research". (Karen Ashe, co-author of the main paper referenced here, also stops by the thread.)
[1] https://www.alzforum.org/news/community-news/sylvain-lesne-w...
civilized|3 years ago
We can blame regulatory capture of the FDA for approval of failed drugs, rather than the scientific establishment. And we can blame Sylvain Lesné for Sylvain Lesné's fraud.
I would encourage those of us whose only knowledge of this topic is the word "amyloid" (I admit I am one of them) to read the scientists' comments and appreciate that there is more to this than we know. There are complexities, nuances, diverse perspectives and healthy disagreements. It's not just a political battlefield. Projecting culture war into it would be harmful to the scientific progress we all value and to the millions who suffer from Alzheimer's.
kasabali|3 years ago
Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) https://news.ycombinator.com/item?id=31828509
How an Alzheimer’s ‘cabal’ thwarted progress toward a cure https://news.ycombinator.com/item?id=21911225
The amyloid hypothesis on trial https://news.ycombinator.com/item?id=17618027
Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) https://news.ycombinator.com/item?id=17444214
Why, at this point should we believe any one scientist writing in that forum wasn't already sunk far deep into amyloid research in their career?
Not to mention that after a quick glance on the comments section, I fail to see where you get the idea that "They all disagree with the notion that Lesné's papers have been important to the field". Apart from the very first comment from karen Ashe (who will obviously be defending her research) and a few other who's working on related topics, other commenters seems to be keeping their suspicion at amyloid hypothesis.
ncmncm|3 years ago
[deleted]
plutonorm|3 years ago
atombender|3 years ago
[1] https://www.dailykos.com/stories/2022/7/22/2111914/-Two-deca...
conchrat|3 years ago
[1] https://www.science.org/content/article/potential-fabricatio...
pigtailgirl|3 years ago
https://www.science.org/content/article/potential-fabricatio...
kurupt213|3 years ago
unknown|3 years ago
[deleted]
formerly_proven|3 years ago
nonrandomstring|3 years ago
Academia and research needs a new broom. Presently incentives are peverse. Impact factors, publisher corruption, grant applications and funding are a blight on science.
rawoke083600|3 years ago
aaomidi|3 years ago
My opinion: capitalism has corrupted literally every single thing it has touched.
photochemsyn|3 years ago
https://physicstoday.scitation.org/doi/full/10.1063/1.324848...
A key point, from the above review, that I think explains a lot of this behavior:
> "Reich points out that fraudsters like Schön could get credit for “first discovery” if, before they are caught, their false claims are confirmed by others on the basis of genuine data."
It did shake up the field of organic semiconductor device research in physics by increasing scrutiny and changing some requirements (for example, electron microscope imagery of claimed devices is now a requirement for publication). However, as the top post at present notes, the incentives are backwards in academic science these days, and the role of funding organizations and high-profile journals is as problematic as that of the originating fraudsters.
Maybe this instance of fraud will do the same for the biomedical field, by forcing researchers to release their raw data and full-resolution images as a condition of publication, although that would require a major shift in behavior in today's patent-driven startup-centered heavily-corporatized biomedical research world.
Personally, I'll note that during the years I worked in academia, of the three PIs I worked with, I discovered two engaging in fraudulent research to greater or lesser extent. The main differences between them and the one who wasn't were (1) lab notebook discipline and recording and storing data securely, (2) in-house replication was required, (3) no toleration for BS and shady behavior. The others broke all those rules. (Unfortunately I picked the wrong PI to work with, and ended up leaving academia in a fit of contemptuous disgust.)
A good rule of thumb: If some research claim hasn't been replicated, and if the data and methods aren't transparently available, then it's as likely to be fraudulent garbage as not, and it's not worthy of further examination.
Calavar|3 years ago
chki|3 years ago
marcosdumay|3 years ago
bencollier49|3 years ago
Fraud by false representation
(1) A person is in breach of this section if he—
(a) dishonestly makes a false representation, and
(b) intends, by making the representation—
(i) to make a gain for himself or another
kyouens|3 years ago
verisimi|3 years ago
It really lays open how easy it is to mislead everyone. All these siloed scientists won't have a clue anything is wrong. This is how conspiracies would work... if there is advantage to someone somewhere and they have the means to alter the model in their favour, why wouldn't they?
onionisafruit|3 years ago
I suspect there was deliberate fraud, but this article doesn't provide any more evidence of that than previous articles.
> Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. Meaning that patients who did die from Alzheimer’s may have been misdiagnosed as having something else. Those whose dementia came from other causes may have falsely been dragged under the Alzheimer’s umbrella.
I think the author is confused about the controversy he is reporting on. Nobody is suggesting that there aren't elevated levels of Aβ in Alzheimer's brains. The controversy is only about the presence of Aβ56, and as far as I know Aβ56 was never used to diagnose Alzheimer's disease. It should also be noted that this is only relevant to postmortem diagnosis, so even if they were testing for Aβ*56 it wouldn't have affected the diagnosis of living patients.
At the bottom of the article is a note, "Article written by Mark Sumner via Daily Kos". This explains a lot. Daily Kos is a site that got its start with sensationalized political articles. Now they've apparently expanded to subjects where they can do more damage.
---
As I post the comment, the title of the linked article is: "Two decades of Alzheimer’s research was based on deliberate fraud by 2 scientists that has cost billions of dollars and millions of lives"
[0] https://www.science.org/content/article/potential-fabricatio... [1] https://news.ycombinator.com/item?id=32183302
unknown|3 years ago
[deleted]
api|3 years ago
People do this all the time. In fact I’d say it’s the usual reaction when confronted with data contradicting one’s beliefs.
Scientists are supposed to learn to go past that but I wonder how many actually do, especially when there is both social and economic pressure to conform to a school of thought.
xbar|3 years ago
throwaway6734|3 years ago
ncmncm|3 years ago
These people need to be formally immediately banned from any NIH activity, and criminally charged. We have known for years that their crap work was useless.
BurningFrog|3 years ago
w-m|3 years ago
„I sincerely doubt that the absence of this particular paper and AB*56 from historical scientific record would have significantly changed the last 20 years of AD drug development. That is because there is strong genetic and other evidence for the role of amyloid in disease.“
bigDinosaur|3 years ago
lettergram|3 years ago
Highly recommend this book to discuss why: https://www.amazon.com/Rigor-Mortis-Science-Worthless-Billio...
It all comes down to incentives.
(1) As a researcher you lose funding m if you don’t produce
(2) funds aren’t allocated to reproduce
(3) Researchers who publish will block research that disagrees with their work (as they’re also reviewers) (will lose future funding / have more competition)
(4) Researchers wont rescind their work if later findings warrant it (no incentive to)
(5) N numbers are way too low (higher N is more money)
codethief|3 years ago
Maybe that's the case in your area of research. In mine (math, physics) it definitely isn't. So I would be a bit more careful about the wording here. ("80% of science" – what science?)
ad404b8a372f2b9|3 years ago
But after becoming a scientist, coming across so many fraudulent papers, so much non-reproducible and poorly done research. And seeing how it's affected my own, the thing that's dearest to me, having to build on top of those results and work in that global environment. It's been heart breaking, I feel no love for science anymore.
dahart|3 years ago
There is no question that a very significant portion is wrong and some of it is fraud, but I feel like this is the wrong summary takeaway. Science isn’t the reason that science is messed up, people are the reason. All fields of human endeavor suffer from the same problems due to emotional and political and selfish people. It’s more like, welcome to humanity. Science is actually the best thing we’ve got, there is no alternative that has less BS and more truth. The 10% or so of science that’s right has transformed the earth in the last century.
I worry about framing this the right way, about the subtleties of how you say it, because there is currently a war being waged on public trust in science, and to some degree that anti-science war is being won. It’s potentially damaging to say “most of science is wrong” and just stop there. That’s a misleading framing in my opinion. In order to fix the funding problems, society as a whole needs to have trust in science, to believe that the majority of people doing science are politically impartial and also not wasting money or lining their own pockets, to believe that scientific progress is human progress.
It’s important to note that the incentive problems you cite mostly aren’t caused my any malicious intent. Disagreeing with someone else’s research, in my experience, isn’t often done with the primary goal of holding back good research, it’s done because the researchers actually disagree on the science, and the reviewer actually believes the proposed paper isn’t complete or correct or up to publication standards. Moreover, for science it’s very important for researchers to be critical of each other. That is part of why we need more replication study.
orzig|3 years ago
Even $5 to someone with a long history of finding scientific fraud puts you on the right side of history: https://www.patreon.com/elisabethbik
I’ve been donating for years and I’ve never been more proud of that decision.
ta988|3 years ago
FredPret|3 years ago
That way the only possible competition will be number of citations. The pressure will be for quality, not quantity.
api|3 years ago
It’s probably about the worst in any field dominated by studies and statistics. Harder sciences are harder to fake as bad results can be more conclusively falsified.
pcurve|3 years ago
He said something exactly the same, and his conscious wouldn't allow him to work in the field of science.
He left the field many years ago. He delivers mails now.
Gimpei|3 years ago
synu|3 years ago
Calavar|3 years ago
endgame|3 years ago
Humans are not incentive-following automata, though we have incentive-following tendencies.
redeeman|3 years ago
OrangeMonkey|3 years ago
nonrandomstring|3 years ago
This is the biggest problem in my view. My work in R&D taught me that most of the time we don't produce anything. It's high risk. But it's high in rewards, often in adjacent areas not primarily the focus of the initial brief.
Surely all serious investors understand this. Research is something we do for marginal returns. It's not an "innovation factory". With things currently stacked against risk, research can only yield tepid results.
stewbrew|3 years ago
zeristor|3 years ago
It would appear that this isn’t really “Science” if the ideal of research is being veered away from so much.
Vested interests suffocating the process.
rgrieselhuber|3 years ago
throwawaymaths|3 years ago
hownottowrite|3 years ago
unknown|3 years ago
[deleted]
hammock|3 years ago
[deleted]
themitigating|3 years ago
aaron695|3 years ago
[deleted]
qwertyuiop_|3 years ago
[deleted]