Abdelrahman
Progress in finding a cure for Alzheimer’s disease has been frustratingly gradual. Over the years, billions of pounds have been allocated to combat this unforgiving condition, which ranks as one of the primary causes of mortality in the UK.
The intricate nature of the human brain significantly contributes to this challenge. The mechanisms through which its vast network of neurons create memory, consciousness, and personal agency remain largely elusive. However, in his insightful new book, Doctored, journalist Charles Piller suggests that a more troubling element has hindered advancement: “decades of arrogance, greed, fabrication, and mistakes have drained research funding and strewn the drug development arena with countless failures.”
Piller, an expert in investigative journalism, contributes to Science, one of the leading scientific publications globally. His reputation means that for any researcher engaging in unethical behavior, his probing inquiries are likely the last they would want to encounter. In Doctored, he shares his meticulous investigative approach and presents numerous instances of alleged scientific misconduct, including cases tied to significant Alzheimer’s research that may have diverted the path towards effective treatments.
At the heart of Piller’s narrative lies the prevalent theory surrounding Alzheimer’s etiology: the “amyloid hypothesis.” This theory posits that the disease, characterized by symptoms like memory loss, disorientation, and hallucinations, is primarily triggered by the buildup of two critical proteins. The first, amyloid, forms sticky aggregates called oligomers that cluster into larger plaques on brain cell surfaces. The second, tau, creates twisted tangles within neurons.
For decades, the amyloid hypothesis has dominated Alzheimer’s research. By the mid-2000s, Dennis Selkoe, a Harvard professor and staunch supporter of this theory, had emerged as the most cited researcher in the field. However, skepticism began to surface as post-mortem studies revealed substantial amyloid and tau deposits in the brains of elderly individuals who exhibited no signs of dementia or cognitive decline. This raises questions: Could the accumulation be a symptom rather than a cause? Were researchers proposing alternative views being marginalized by an “amyloid mafia” of entrenched senior scientists?
As Piller recounts, a pivotal study surfaced in 2006, which appeared to reinforce the amyloid hypothesis. Conducted by Karen Ashe and her protégé, Sylvain Lesne, at the University of Minnesota, the research claimed they identified a specific type of amyloid, referred to as Aβ*56, in genetically modified mice that exhibited Alzheimer’s-like symptoms. They reported that Aβ*56 levels corresponded with cognitive decline and that injecting rats with this substance led to memory issues.
Ashe asserted in a blog that she had discovered “the first substance ever identified in brain tissue in Alzheimer’s research that has been shown to cause memory impairment.” The paper was extensively cited, with nearly 2,500 references, establishing it as a landmark work in Alzheimer’s research.
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However, in 2022, Piller, with the assistance of neuroscientist and physician Matthew Schrag from Vanderbilt University, published a groundbreaking article in Science revealing that key results in Ashe’s study were manipulated. Although Ashe maintained that these alterations did not affect the study’s conclusions, her paper was eventually retracted in June of last year. Other studies, including one suggesting increasing Aβ*56 levels with age, have since been corrected. Meanwhile, rival scientists have expressed frustrations over their inability to detect Aβ*56 in human tissue samples.
Moreover, Piller sheds light on Eliezer Masliah, a prominent figure appointed in 2016 to lead a significant US government initiative on Alzheimer’s. With around 800 papers to his credit, many regarded as influential, Masliah was seen as an ideal candidate for this role, which came with substantial funding. Yet in a recent examination, Piller revealed that Masliah’s research was marred by improperly edited images of brain tissue and “apparent falsified Western blots,” which are used to indicate protein presence. Masliah has been invited to provide a statement by The Times.
Piller also scrutinizes the biopharmaceutical company Cassava Sciences, which announced in November that its experimental Alzheimer’s drug, simufilam, failed to show efficacy in a phase 3 clinical trial, marking the end of a controversial treatment. A law firm representing whistleblowers had previously filed a petition with the FDA in 2021, claiming that some studies backing the drug’s advancement to human testing contained fraudulent images.
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In 2023, Piller disclosed that one of the neuroscientists involved in the simufilam research faced findings of “egregious misconduct” from a university panel and was subsequently indicted by the US Department of Justice for defrauding the National Institutes of Health of approximately $16 million in related grants. In a separate incident, Cassava agreed to pay $40 million to the Securities and Exchange Commission to resolve charges of misleading investors regarding prior clinical trial results.
Why would scientists resort to deception? The motivations resemble those of others: financial gain and prestige. However, Piller highlights that the dominance of the amyloid hypothesis has cultivated a culture where funding, corporate benefits, career progress, and professional reputations often hinge on a widely accepted narrative, maintained on shaky faith. It’s easier, he notes, to publish questionable findings that conform to a flawed consensus than challenge entrenched beliefs.
Indeed, Piller makes a significant observation. While researchers have developed drugs that effectively remove amyloid from the brain, these treatments have yet to demonstrate a reversal of Alzheimer’s disease. The most encouraging trials have produced only modest results, often imperceptible to patients and caregivers. Moreover, these medications can pose serious risks, including a condition known as “Aria,” which refers to “amyloid related imaging abnormalities,” a euphemism for potentially fatal cerebral hemorrhaging.
One treatment, aducanumab, initially hailed as a groundbreaking solution, was withdrawn last year after failing to generate substantial revenue in the US, where healthcare providers refrained from prescribing it, and insurers declined to cover its steep annual cost of $56,000 per patient. Although it gained approval in the US, this may reflect the compelling sway of the amyloid hypothesis, yet biology remains untouchable in the long run.
As one of Piller’s sources aptly stated, it’s impossible to deceive a disease.
Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s by Charles Piller (Icon £20, 352 pages). For more information or to purchase, visit timesbookshop.co.uk. Enjoy free standard UK delivery on orders over £25 and exclusive discounts for Times+ members.
