Centralized research funding (often centralized by government agencies) reduces the pluralism of ideas and methods that often lead to breakthrough innovations. The story of Alzheimer’s research, quoted below, is a dramatic case-in-point.
A secondary related lesson from the story quoted below is that Dr. Thambisetty, one of the outsiders struggling to make a difference, is trying to evade the enormous costs of mandated phase 3 clinical trials, by only investigating drugs that already have been approved by the FDA for use against other conditions. With his severely limited funding, and the huge costs of mandated phase 3 clinical trials, this may be a shrewd strategy for Thambisetty, but notice that by following it, he will never explore all the as-yet-unapproved chemicals that might include the best magic bullet against Alzheimer’s.)
(p. A25) What if a preposterous failed treatment for Covid-19 — the arthritis drug hydroxychloroquine — could successfully treat another dreaded disease, Alzheimer’s?
Dr. Madhav Thambisetty, a neurologist at the National Institute on Aging, thinks the drug’s suppression of inflammation, commonly associated with neurodegenerative disorders, might provide surprising benefits for dementia.
It’s an intriguing idea. Unfortunately, we won’t know for quite a while, if ever, whether Dr. Thambisetty is right. That’s because unconventional ideas that do not offer fealty to the dominant approach to study and treat Alzheimer’s — what’s known as the amyloid hypothesis — often find themselves starved for funds and scientific mind share.
Such shortsighted rigidity may have slowed progress toward a cure — a tragedy for a disease projected to affect more than 11 million people in the United States by 2040.
. . .
. . ., in 2006, an animal experiment published in the journal Nature identified a specific type of amyloid protein as the first substance found in brain tissue to directly cause symptoms associated with Alzheimer’s. Top scientists called it a breakthrough that provided a key target for treatments. The paper became one of the most cited in the field, and funds to explore similar proteins skyrocketed.
. . .
In 2022, my investigation in Science showed evidence that the famous 2006 experiment that helped push forward the amyloid hypothesis used falsified data. On June 24 [2024], after most of its authors conceded technical images were doctored, the paper was finally retracted.
. . .
In reporting for my forthcoming book about the disturbing state of play in Alzheimer’s research, I’ve spoken to many scientists pursuing alternatives. Dr. Thambisetty, for example, compares brain tissues from people who died in their 30s or 40s with and without genetic risk factors for Alzheimer’s. He then compares these findings to tissues from deceased Alzheimer’s patients and people who didn’t have the disease. Where changes overlap, drug targets might emerge. Rather than develop new drugs through lab and animal testing, followed by clinical trials that cost vast sums — a process that can take decades — he examines treatments already approved as reasonably safe and effective for other conditions. Patent protections have lapsed for many, making them inexpensive.
Experiments have also begun to test the weight-loss drug semaglutide (sold as Wegovy, among other brands). Researchers hope that results due in 2026 will show that its anti-inflammatory effects — like Dr. Thambisetty’s idea about hydroxychloroquine — slow cognitive decline.
Ruth Itzhaki, a research scientist at the University of Oxford, stirred curiosity in the 1990s when she shared evidence tying Alzheimer’s to herpesvirus — a scourge spread by oral or genital contact and often resulting in painful infections. For years, powerful promoters of the amyloid hypothesis ignored or dismissed the infection hypothesis for Alzheimer’s, effectively rendering it invisible, Dr. Itzhaki said with exasperation. Research suggests that viruses may hide undetected in organs, including the brain, for years, causing symptoms divergent from the original infection.
. . .
Sometimes a disease stems from a single clear-cut origin, such as genetic mutations that cause deadly sickle cell disease. “But very few diseases of aging have just one cause. It’s just not logical,” said Dr. Matthew Schrag, a neurologist at Vanderbilt University Medical Center. Working independently of his university, he discovered the 2006 research image manipulations.
. . .
“There is an entrenched echo chamber that involves a lot of big names,” Dr. Schrag said. “It’s time for the field to move on.”
For the full commentary see:
(Note: ellipses, and bracketed year, added.)
(Note: the online version of the commentary has the date July 7, 2024, and has the same title as the print version. Where there are a couple of small differences in wording, the passages quoted above follow the online version.)
Piller’s paper in Science, mentioned above, is:
Piller, Charles. “Blots on a Field?” Science 377, no. 6604 (July 2022): 358-63.
Piller’s commentary is related to his forthcoming book:
Piller, Charles. Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. New York: Atria/One Signal Publishers, Forthcoming on February 4, 2025.