Yang Jing Mingmin from Aofei Temple
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The pioneering work published on Nature in 2006 is now exposed to be fake!
Science's latest special report disclosed that the paper experimental results have traces of tampering .
's worst impact is that it will mislead research in the field for 16 years since the century.
This paper directly proves an important hypothesis for Alzheimer's disease research. To this day, the number of citations has exceeded 2300 times.
, its direct beneficiary, the first author, later received huge support: it received $774,000 in funding and $7 million in subsidies in four years, with a total of more than 52 million in funding. As soon as the
news came out, it caused an uproar in an instant: shocked the whole science.
Some people are also worried that such a big "academic explosion" will affect students in related fields that cannot graduate.
However, there are also a group of netizens who are not interested in watching the fun: Science and Nature fight!
Then Cell is probably the first place in the melon table. (Doge)
However, here we still have to say "fair" for Science, because they also found that more than 20 papers in the party's work had data fraud, not just Nature.
paper experimental diagram has traces of tampering
The core paper involved in this time was published in Nature in 2006.
paper proposes that a specific beta-amyloid oligomer Aβ*56 can damage brain memory and may be a key substance in inducing Alzheimer's disease.
researchers said that they found this substance in transgenic mice , extracted and purified it and injected it into young and healthy mice. The results showed that the mouse's memory function showed a decrease in .
At that time, the discovery of this substance provided strong evidence for the amyloid hypothesis .
The hypothesis proposes that in the brain of Alzheimer's patients, the oligomers formed after amyloid (Aβ) accumulate will form plaques, resulting in neuronal fiber tangles and neuronal loss.
But judging from the current investigation results, the key results of the Aβ56 experimental results in this paper are suspected of major fraud - there is almost exactly the same band in the experimental results of
.
For the part circled in the red box in the figure, the investigators calculated the strength of the relationship between the two rows of bands, and the results showed that its correlation reached 0.98 (1 represents exactly the same) , "it is almost impossible to happen naturally."
In the paper, the author used this result graph to prove that as the age of Alzheimer's mice increases, the level of Aβ*56 in their bodies is also increasing. Elisabeth Bik, a molecular biologist and well-known academic anti-counterfeiter, said that the author may not obtain the expected results at the initial experiment, so the data was tampered with more hypotheses.
This further deepens the academic community's doubts about Aβ*56.
You should know that in the past decade, many experts have been questioning the authenticity of the research on purifying Aβ*56.
Donna Wilcock, an expert in Alzheimer's disease at the University of Kentucky, said that the properties of this oligomer are very unstable and will spontaneously convert to other types of oligomers. The purified sample is likely to be a mixture.
This leads to the inability to reduce memory, which completely attributes to Aβ*56.
Previously, academic circles even questioned whether Aβ*56 really exists. Many laboratories have previously wanted to extract Aβ*56, but few of them have succeeded.
In 2008, Dennis Selkoe, a supporter of the amyloid hypothesis and a well-known Alzheimer's doctor, also mentioned in two papers that he did not find Aβ*56 in the human body.
It is Science's turn to come forward. Not only does the experimental results cannot be reproduced, but it also involves that this "giant's shoulder" may no longer exist.
may mislead global research for 16 years
mentioned earlier that this "founding work" directly verifies the amyloid hypothesis.
After this, the academic and industrial circles began to bet heavily on this.
According to Science News, at that time, the support of NIH (American Institutes of Health) for "amyloid, oligomers and Alzheimer's disease " rose from 0 to US$287 million last year, equivalent to RMB 1.8 billion.
This year, NIH spent about $1.6 billion on amyloid project (about 10.814 billion yuan) . The amount of
directly accounts for half of the total Alzheimer's research fund.
does not count the ideas and thoughts that scientists contribute to this field. Over the past decade, researchers have tried to treat Alzheimer's disease by lowering amyloid proteins. However, according to the book "Cognitive Psychology", their attempts are like riding a roller coaster: the treatments that prove effective in animal models are ineffective in human patients.
△Photo source: Zhihu netizen @Jiang XueqingCherry
In the view of Thomas Südhof, the Nobel Prize winner and Stanford neuroscientist, this is the most direct and obvious damage to .
Zhihu netizen @Junzi Chaoge believes that this fraud has brought the research field of Alzheimer's disease back to 10 years ago, and academics are once again divided into neuroimmune hypothesis, inflammation hypothesis and amyloid degeneration hypothesis.
In addition, it also means that the hypothesis of amyloid can still be falsified . What is confirmed is an subtype of amyloid "Aβ*56"
. For the industry, many pharmaceutical companies have developed drugs based on this hypothesis. You should know that new drugs have high cost and long cycles. If the drug cannot prove effective, all processes will be meaningless.
It is worth mentioning that the initiator of this investigation is due to a question about drug research.
comes from Vanderbilt University's 's eldest brother Matthew Schrag, who had previously gained a reputation for criticizing an Aβ anti-drug approved by FDA, and he found a like-minded lawyer.
The lawyer is investigating Simufilam, a drug currently being tested in clinical trials, and the developer claims that the drug can improve cognitive ability by repairing a protein that blocks Aβ deposition.
and they suspected that the research behind this was fraudulent, so they used the existing medical knowledge reserve to conduct an investigation.
However, some netizens believe that this fraud will not have much impact. What the industry currently recognizes is the relationship between Aβ*42 and Alzheimer's disease.
Harvard University neurologist said that although the Aβ*56 result is doubtful, I hope everyone will not completely give up on the amyloid hypothesis.
However, he also mentioned that if several clinical drug experiments have failed now, this hypothesis may be hidden.
At present, Nature has issued a statement to start investigating this paper. A spokesperson for the school where the research team belongs to , the University of Minnesota, said the school is also reviewing the matter.
It is worth mentioning that the paper was Sylvain Lesné (Sylvain Lesné) was found to be suspected of fraud in this round of academic counterfeiting.
has 10 articles related to Aβ*56. The
investigation results show that there are at least 12 experimental results pictures in these papers, which are suspected of major fraud.
Dennis Selk, a well-known doctor in the field of Alzheimer's disease, said bluntly:
I think (these pictures) have no other reasonable explanation except for artificial manipulation.
At the same time, some scholars also revealed that in a past collaboration with Sylvain Lesné, he found that the images he provided were very suspicious, so he asked students to reproduce the experiment, but they all failed in the end. After
, he questioned Sylvan, and the other party firmly denied it.
Finally, the co-authored paper was withdrawn before publication, and the scholar also broke off diplomatic relations with Sylvan.
Corresponding author: I still have confidence in Aβ*56
According to Science, the paper's corresponding author Chinese scientist Karen Ashe (Karen Ashe) refused to accept an interview.
But in the reply email, she said that she was still confident in Aβ*56 and said that she was still studying the relevant content of Aβ oligomer structure.
At the same time, she believes that Science's investigation exaggerates and distorts the impact of the paper on the academic world.
I spent decades studying Alzheimer's disease, but found that one of my colleagues tampered with images and mislead me and the entire academic community.
What is even more heartbreaking is that such an authoritative scientific journal openly distorts my research results.
Asia is a professor of neurology at the University of Minnesota School of Medicine and director of the Alzheimer's Disease Research Laboratory at the school.
In fact, because of this research, Asia won many awards in the field of Alzheimer's disease.
was awarded a $100,000 Potamkin Prize just two weeks after the paper was published.
later received the Alzheimer's Medical Research Award from the Metropolitan Life Foundation, which provides a $550,000 award for html and a $200,000 research fund .
It is reported that Asia has received more than US$28 million (equivalent to approximately RMB 180 million) from the National Institute of Health (NIH). On the other side of
, the paper, Sylvain Lesné, also became famous for this achievement.
In 2009, he set up a NIH-backed laboratory at the University of Minnesota.
008-2012, he received more than $770,000 in funding from the NHS to study Aβ*56, and more than $7 million were used to study Alzheimer's related problems. In 2020, he also became the leader of the University of Minnesota Neuroscience graduate program.
At present, Sylvan has not made any reply to the outside world, and the relevant investigation is still continuing.
Reference link:
[1]https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[2]https://www.star tribune.com/senior-university-of-minnesota-scientist-responds-to-fraud-allegations-in-alzheimers-research/600192351/?refresh=true
[3]https://www.zhihu.com/question/544750364
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