Uh-oh. As I get older, I’d like to think science will come up with treatments for cognitive decline (don’t worry, I’m not showing any symptoms…yet. I don’t think. How would I know?), and Alzheimer’s is serious problem. Judging by the fact that we always get a couple of seminars on Alzheimer’s from our graduating seniors, it’s of concern to even young people. Unfortunately, every prospective drug against the disease seems to flop in clinical trials. It’s entirely possible that 16 years of research has been misled by one study that identified a candidate amyloid protein as the causal agent.
The first author of that influential study, published in Nature in 2006, was an ascending neuroscientist: Sylvain Lesné of the University of Minnesota (UMN), Twin Cities. His work underpins a key element of the dominant yet controversial amyloid hypothesis of Alzheimer’s, which holds that Aβ clumps, known as plaques, in brain tissue are a primary cause of the devastating illness, which afflicts tens of millions globally. In what looked like a smoking gun for the theory and a lead to possible therapies, Lesné and his colleagues discovered an Aβ subtype and seemed to prove it caused dementia in rats.
Why did it have to be the University of Minnesota?
A 6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research. A leading independent image analyst and several top Alzheimer’s researchers—including George Perry of the University of Texas, San Antonio, and John Forsayeth of the University of California, San Francisco (UCSF)—reviewed most of Schrag’s findings at Science’s request. They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky.
The authors “appeared to have composed figures by piecing together parts of photos from different experiments,” says Elisabeth Bik, a molecular biologist and well-known forensic image consultant. “The obtained experimental results might not have been the desired results, and that data might have been changed to … better fit a hypothesis.”
Lesné has gone silent. The university is investigating. Lawyers are, I’m sure, standing by with bated breath.
The evidence is built around Western blots, which are used to resolve individual proteins from a sample. A bunch of the published (and some of the unpublished) data show unmistakeable, unambiguous evidence of tampering, and someone in that lab was clearly going into the data and patching it up to look more convincing. Human eyes aren’t very good at detecting slight variations in a semi-random smear of pixels, but computers excel at it, and the evidence of copy/pasting and merging jump out at you.
Why does anyone pull this kind of crap with their data? If the raw data doesn’t show it, if it can’t be extracted with a statistical analysis of the original image, it doesn’t exist. You can’t compensate for a negative result by artificially pasting the result you wanted in place.
This is a catastrophe. One ambitious researcher faked data in order to get a paper in Nature, and now it’s a quarter billion dollar industry built on a false foundation.
The Nature paper has been cited in about 2300 scholarly articles—more than all but four other Alzheimer’s basic research reports published since 2006, according to the Web of Science database. Since then, annual NIH support for studies labeled “amyloid, oligomer, and Alzheimer’s” has risen from near zero to $287 million in 2021. Lesné and Ashe helped spark that explosion, experts say.
The paper provided an “important boost” to the amyloid and toxic oligomer hypotheses when they faced rising doubts, Südhof says. “Proponents loved it, because it seemed to be an independent validation of what they have been proposing for a long time.”
Great. Forgery and confirmation bias make a terrific pairing.