In August 2021, Matthew Scrag, 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 Similar. 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 (AB), 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 Similar may have been “fraudulent,” according to a petition later filed on their behalf with the U.S. Food and Drug Administration (FDA). Scrag 37, a soft- spoken, nonchalantly rumpled junior professor, had already gained some notoriety by publicly criticizing the controversial FDA approval of the anti-war drug Adult. His own research also contradicted some of Cassava’s claims. He feared volunteers in ongoing Similar trials faced risks of side effects with no chance of benefits
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 Scrag 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 Scrag’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 (UM), Twin Cities. His work underpins a key element of the dominant yet controversial amyloid hypothesis of Alzheimer’s, which holds that A clump, known as plaques, in the brain But Scrag’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 (UM), Twin Cities. His work underpins a key element of the dominant yet controversial amyloid hypothesis of Alzheimer’s, which holds that A clump, 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 A subtype and seemed to prove it caused dementia in rats. If Scrag’s doubts are correct, Lesné’s findings were an elaborate mirage. Scrag, who had not publicly revealed his role as a whistleblower until this article, avoids the word “fraud” in his critiques of Lesné’s work and the Cassava-related studies and does not claim to have proved misconduct. That would require access to original, complete, unpublished images and in some cases raw numerical data. “I focus on what we can see in the published images, and describe them as red flags, not final conclusions,” he says. “The data should speak for itself.”
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