Thousands of researchers have seen these photos. Lay people would think they saw small black beans. Specialists, accustomed to the grain of benchtop photos, know well that these are proteins. None, however, had noticed the deception. It was by chance that Matthew Schrag realized this. This American neurobiologist, professor at Vanderbilt University (Tennessee), was shuffling the scientific literature on Alzheimer’s when he came across this research article, published in Nature in 2006. A hit in the research community; one of the most cited articles in the world. Nothing scandalous, at least at the time.
Matthew Schrag hadn’t asked for anything. Lawyers had chosen him as an expert to carry out verifications about an Alzheimer’s drug. A completely different matter, not really the investigation of the century. But looking back at these photos, very famous in the field, he can’t help but wince. First on this grayish background: why is it similar in all the photos when each one concerns a different experience? And then there are the beans – the proteins – all similar, too perfect. Mother Nature does things well, it’s true, but rarely identically. “It was bogus,” he sums up, with his expert eye.
These accusations, formulated with the necessary consideration for scientific controversy, Matthew Schrag first pointed them out anonymously, on the collaboration platform PubPeer. Then in an investigation by the scientific journal Science, published in July 2022. He decides on this occasion to reveal his name. The writings hit the mark and his doubts have since been relayed by newspapers around the world. But until now, the work in question had not been retracted. It’s almost done: lead author Karen Ashe has just announced that she has submitted a request in this regard.
A sacred monster of literature
Contacted by L’Express, the publishing house, Nature, declares that it is carrying out some final checks. When she makes the retraction, the article will become the most important ever retracted from the scientific literature. More than 2,300 studies relied on these results to build their hypotheses and guide their efforts. Tens of millions of dollars had been invested in an attempt to repeat or improve the findings thus presented. So that ultimately, the paper is considered null and void.
Matthew Schrag hesitated for a long time before emerging from anonymity. “I was risking a lot,” slips the person concerned, white coat screwed on his back, even by videoconference. Revealing the affair could have caused him major problems. “It is difficult to tackle such a monument of research, especially if you are relatively young in the field like Matthew Schrag, weighs Charles Piller, the author of the revelations of Science. But when you put a face behind findings of misconduct, they are much more difficult to ignore, especially on the part of scientific institutions and leaders.”
The study in question helped to highlight the role of β-amyloid plaques in Alzheimer’s disease. Since the 2000s, these protein aggregates have become the main target of drug manufacturers. Scientists believe that they are at the origin of a large part of the symptoms of the pathology, which causes memory loss to the point of senile. These plaques seem to accumulate disproportionately in sick people. Karen Ashe’s work went a step further, and pointed to a subcomponent of amyloid, called Aβ*56.
Behind the frauds, a Frenchman
Once identified by Matthew Schrag, the frauds were confirmed by verifications by another scientist, Elisabeth Bik. All these images point to the same researcher: Sylvain Lesné, a Frenchman, trained at the University of Caen. He had been noticed by Karen Ashe, who had confided to him part of her experiences. Many of his works were subsequently highlighted by Matthew Schrag. He is convinced, they too have been distorted. Sylvain Lesné did not respond to L’Express’s requests. In the absence of a response from him, it is difficult to know for what purpose these images were modified.
Sometimes scientific fraud is so blatant that it is possible to say that the entire work was invented. Here it is not clear. For a long time, Karen Ashe, a leading authority on neurology, retorted that, although there seemed to be problems, these elements were not such as to call into question her entire article. This only deserved a simple correction, said the American. Her request for retraction shows that she has changed her mind. And in fact, the precise results of his article had never been reproduced.
Sylvain Lesné’s thesis supervisor, Denis Vivien, cuts short our requests to find out more about this researcher and his reasons: “He must answer for his actions himself. I cut ties with him a long time ago.” In 2022, he indicated to Science having withdrawn an article with him before publication, because of suspicions of the genre. And hasn’t been more talkative since. An investigation was launched by the university which employs Sylvain Lesné, that of Minnesota. His boss, Karen Ashe, would not have participated directly in the falsifications, according to the results of a previous investigation by the same authorities. The fact remains that she is responsible for what happens under her direction.
Beautify, or make up?
According to whistleblower Matthew Schrag, the cheating was at least intended to “embellish” the study, to make it appear more rigorous than it was. Some researchers are sometimes tempted to remove visual defects linked to impurities on measuring devices. But the expert cannot rule out something more serious: “Maybe there were only imperfections, but in that case, why take the risk of being caught red-handed?” asks the expert. And even if the cheating is only cosmetic, the neurobiologist insists: “These practices are unacceptable in the context of scientific work.”
This request for retraction comes after a series of reversals for Alzheimer’s research. Several drugs have proven to be more dangerous than expected, including Leqembi, once considered a potential therapeutic revolution. And above all, another important study was withdrawn at the end of 2023 by Science. It led to the resignation of the person responsible for this work, Marc Tessier-Lavigne, then president of one of the largest American universities, Stanford, located in California.
A scientific hypothesis is never based solely on a single article. Karen Ashe’s retraction alone cannot call into question the amyloid plaque trail. The fact remains that this is being shaken up: “It turns out that at the same time, numerous studies have shown that it is not enough to attack this phenomenon to fight against Alzheimer’s. There are now molecules capable of removing them, and yet many patients continue to decline”, summarizes Nicolas Villain, neurologist at the Pitié Salpêtrière hospital (AP-HP) in Paris.
The risk of a cold on this research
Until very recently, Karen Ashe still believed in her results, which have now fallen to the level of hypotheses: “I continue to think that Aβ*56 could play an important role in Alzheimer’s disease and that targeting its elimination could lead to significant clinical benefits,” she posted on PubPeer in May, citing several subsequent findings based on this work. Without succeeding in preventing the fall of one of the queens of Alzheimer’s studies.
So many incidents so close together risk making new investors a little more cautious than in the past. At least to develop drugs based on these specific avenues. “We are at a crucial moment for Alzheimer’s research. We must become absolutely intolerant of these frauds and ensure that there are no more of them,” said Matthew Schrag. 225,000 people Alzheimer’s patients are diagnosed every year, in France alone. Molecules have arrived on the market, but their effect is limited. Research must continue.
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