I’ve worked as support staff in college and university science departments most of my adult life, and only two times have I witnessed what happens when solid evidence comes to light that a respected researcher in a department might be falsifying data.
It’s the equivalent of an all-hands-on-deck university emergency. The department mobilizes. The highest levels of university leadership get involved. Campus police are called and the lab where the suspect researcher works is locked down, as are any lab notebooks, computers or other research materials. Then the university lawyers get involved and the suspect researcher takes a sudden leave of absence.
So when I read yesterday that the highly respected journal Science had published a story questioning the work of an Alzheimer’s researcher so respected that much of all the research done on Alzheimer’s is based on his work, I knew that this is going to turn out to be a paradigm-shifting scandal.
In August 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, got a call that would plunge him into a maelstrom of possible scientific misconduct. A colleague wanted to connect him with an attorney investigating an experimental drug for Alzheimer’s disease called Simufilam. The drug’s developer, Cassava Sciences, claimed it improved cognition, partly by repairing a protein that can block sticky brain deposits of the protein amyloid beta (Aβ), a hallmark of Alzheimer’s. The attorney’s clients—two prominent neuroscientists who are also short sellers who profit if the company’s stock falls—believed some research related to Simufilam may have been “fraudulent,” according to a petition later filed on their behalf with the U.S. Food and Drug Administration (FDA).
Schrag, 37, a softspoken, nonchalantly rumpled junior professor, had already gained some notoriety by publicly criticizing the controversial FDA approval of the anti-Aβ drug Aduhelm. His own research also contradicted some of Cassava’s claims. He feared volunteers in ongoing Simufilam trials faced risks of side effects with no chance of benefit.
So he applied his technical and medical knowledge to interrogate published images about the drug and its underlying science—for which the attorney paid him $18,000. He identified apparently altered or duplicated images in dozens of journal articles. The attorney reported many of the discoveries in the FDA petition, and Schrag sent all of them to the National Institutes of Health (NIH), which had invested tens of millions of dollars in the work. (Cassava denies any misconduct [see sidebar, below].)
But Schrag’s sleuthing drew him into a different episode of possible misconduct, leading to findings that threaten one of the most cited Alzheimer’s studies of this century and numerous related experiments.
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. If Schrag’s doubts are correct, Lesné’s findings were an elaborate mirage.
I literally got goose bumps when I read that the first time. I got them just now when I read that passage again.
People have died in Alzheimer’s clinical trials testing drugs that have been treating the entirely wrong symptom.
Drug companies — and the federal government — have spent untold billions looking into how to treat a hallmark of Alzheimer’s that might be nothing more than an artifact rather than the root cause of the disease.
And the field of Alzheimer’s research has likely been set back decades as everyone went on a scientific wild good chase.
This is so crazy to almost be unbelievable.
At least we likely now know why so many Alzheimer’s drugs that successfully treat amyloid plaques in the brains of Alzheimer’s patients have failed so miserably at stopping the disease.
You can read the rest of Charles Piller’s article in Science at this link.