Doctored. By Charles Piller. Atria; 352 pages; $28.99. Icon Books; £20
Alzheimer’s disease affects more than 30m people worldwide, mostly the elderly. After the age of 65, the chance of developing it doubles every five years. By 85, the odds are one in three. Its symptoms, which include memory loss, difficulty with basic tasks and depression, progressively worsen. As global life expectancy rises, so will cases of Alzheimer’s, making it one of the big public-health challenges of an ageing world.
There is no cure. Between 1995 and 2021, around $42bn was poured into more than 1,000 clinical trials. Yet only a handful of drugs has made it to market. Even those mostly treat the symptoms of the disease, rather than stop it.
The leading explanation of Alzheimer’s is the “amyloid hypothesis”, which suggests that deposits of beta-amyloid, a type of protein, accumulate between neurons and disrupt their function. But the theory remains controversial: all brains with Alzheimer’s show beta-amyloid plaques, yet not everyone with these plaques experiences cognitive decline. Whether amyloid build-up causes Alzheimer’s, or is merely a symptom, remains unresolved.
In “Doctored” Charles Piller, a science journalist, details how groupthink and dishonesty steered Alzheimer’s research off course. In 2006 a Nature paper by researchers at the University of Minnesota appeared to provide a major breakthrough. The study claimed that a subtype of beta-amyloid caused memory impairment. It quickly became one of the most cited papers and inspired hundreds of millions of dollars in public-research grants. Another influential paper published in 2012 by scientists associated with Cassava Sciences, a biotech firm, bolstered the amyloid theory by linking insulin resistance to amyloid plaque formation. The finding fuelled a wave of research into the idea of Alzheimer’s being a “diabetes of the brain” that could be managed with drugs. There was just one problem—both studies were based on falsified data.
“Doctored” follows Mr Piller’s investigation into the deception. Central to the story is a group of image sleuths, with a sharp eye for manipulated pixels of Western blots (a lab technique used to study proteins, which were doctored in the studies). Some chapters read like a scientific whodunnit. In one, Mr Piller has to work hard to earn the trust of a reluctant whistleblower. In another, he travels to Prague for a private meeting with a group of image detectives with cryptic pseudonyms.
Despite clear evidence of manipulated research results, journals and regulators were slow to act. Mr Piller blames powerful backers of the amyloid hypothesis who ignored red flags. It was only in June 2024—two years after allegations first surfaced—that the Nature paper was retracted by its authors. Cassava Sciences, while denying wrongdoing, stopped trials of its Alzheimer’s drug, Simufilam, in November after it failed to show clinical benefits.
These papers’ consequences go beyond the lab. For patients and their families, experimental treatments often represent a final lifeline. Encouraging people to pin their hopes on medicines that are ineffective, or even unsafe, is a betrayal. Fixation on a theory offering limited success in human trials may also have diverted resources from other more promising therapies.
Since 2023 the Food and Drug Administration, America’s drug regulator, has approved two new medicines that modestly slowed cognitive decline by attacking the amyloid plaques. They also come with dangerous side-effects for some, which include brain swelling and bleeding. Mr Piller remains sceptical of these treatments. So will many of his readers, after his gripping story of medical groupthink and warped incentives. ■
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