Grill J, Rabinovici GD. The Bad Medicine of Doctored. JAMA. 2025 Mar 17. JAMA online
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Grill J, Rabinovici GD. The Bad Medicine of Doctored. JAMA. 2025 Mar 17. JAMA online
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Institute of Neurology, UCL
On February 10, 2025, Nature commissioned a book review of Charles Piller’s “Doctored” from me. On March 19, Nature reversed itself, declining to publish it, as “your review might be perceived as blowback.” Free to publish the review elsewhere, I post a revised version here.
Scientific progress depends on honesty. The work in a scientific paper must be reported honestly so that others can draw the correct conclusions when they read it. This is doubly important when clinical decisions are made based upon the reported data. Recently, there have been a rash of high-profile reports of fraud, some of which have been previously reported by Mr Piller in the Daily Mail, The New York Times, Science, and many other publications.…More
The casual reader may wonder what causes a fraudulent scientist to betray his or her colleagues and why have there been so many recently exposed cases. The question of motive is difficult to answer. Ambition is an obvious cause, but that can vary from a desperate student needing one more piece of data to finish their Ph.D. before the money runs out, to a senior scientist with a long line of fraudulent publications. In my experience, another motive is investigators (one hesitates to call them scientists) who “know what the answer is” and want to show data to “prove them right.” I suspect it is often a mixture of motives.
It seems that once an investigator has started down the slippery slope of fraud, they keep going down it. As to why there have been more recent cases, the easy answer is that work pressures have grown. That may be so, but another factor is the availability of image recognition software which has enabled detection of fraudulent and duplicated histological and western blot images from years, sometimes decades, gone by. Many types of fraud are still undetectable, perhaps above all biased data selection for publication.
A book discussing these issues would be very welcome. Alas, they do not feature in Mr. Piller’s book. Rather, this book conjures alleged downstream consequences of fraud presaged by the subtitle “Fraud, Arrogance and Tragedy in the Quest to Cure Alzheimer’s Disease.” It insinuates that much of the fraud has been perpetrated on behalf of an arrogant “cabal” of researchers supporting the amyloid hypothesis.
As a named member of this cabal, I reject this characterization. I was attracted to genetic analysis precisely because it is agnostic as to disease cause. We declared our support for the amyloid hypothesis when we and our colleagues and competitors identified amyloid mutations as one cause of disease and then mutations in the amyloid metabolizing presenilin protein as another. More recently, we have identified that the risk of late-onset disease is largely predisposed to by deficiencies in amyloid clearance. Piller barely mentions that there is a large body of converging evidence, from dozens of laboratories all over the world, supporting the amyloid hypothesis.
While Piller details a handful of cases of likely fraud, only one, that of Sylvain Lesné at the University of Minnesota, is “amyloid related.” It relates to a 2006 Nature paper from Lesné announcing a particular form of amyloid, designated Aß*, as being the neurotoxic form of amyloid. It is worth noting that the scientific method is, to some extent, self-correcting. This work was never replicated and, soon after it came out, the hallway discussions at Alzheimer meetings and, to a lesser extent, in public fora noted it with profound scepticism. We never cited this work in our review of the amyloid hypothesis, nor did the other major reviews. Dr. de Strooper (another “cabal member”) had cited it only in his critical review “The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes.” Contrary to Piller’s claim, this paper had no great influence in our field.
The Lesné paper exemplifies the old way that science dealt with incorrect and unreliable work. In the absence of replication, together with private conversations, such papers used to quietly die. Now they are being publicly murdered. I am not sure which is the better way. True, we need to more quickly and openly refute and remove wrong papers from the literature. But also, today’s public shaming conflicts with the notion of innocent until proven guilty, and I worry that one day, we will see a suicide by someone judged in the court of public opinion. There are no easy answers.
What was the consequence of this fraud? No doubt, several labs lost time and several millions of dollars were wasted immediately after its publication in replicative attempts. A serious matter, but that is as far as it goes.
Piller then alleges, without even a basis in logic, much less evidence, that this and the other frauds he outlines (which were in studies of Parkinson’s, stroke, metabolism, prions, and a cytoskeleton drug target) reinforced the amyloid hypothesis in a way that hobbled the quest for Alzheimer drugs. This is false on two levels. First, even the Lesné paper was soon informally debunked, and the other papers do not pertain to the amyloid hypothesis. Second, this book comes out just as unbiased regulatory authorities across the globe have approved two anti-amyloid drugs, lecanemab and donanemab, for use to slow Alzheimer progression. Rather than quote these approvals, Piller quotes peripheral naysayers of the amyloid hypothesis who emphasize the rare but serious side effects of these treatments. The risk/benefit relationships of these drugs are a serious issue that is being appropriately discussed by regulators and in public fora: a book by a non-expert on tour is not the correct forum for it. Some of the naysayers Piller relies on heavily in his book have forged their career and, one suspects, their identity, around attacking the amyloid hypothesis. If in search of a cabal, Piller might look there.
Science requires peer-reviewed publications, and as these cases illustrate, the peer review process can be cheated. But it is still better than unreviewed assertions which this book is full of. I have been surprised by the book coming out just as the first imperfect treatments for Alzheimer’s are entering clinical practice. I hope the book and its attendant publicity do not dissuade patients who may benefit from the drugs from seeking help. My biggest disappointment, however, is that this work was first published with the imprimatur of Science Magazine and the AAAS in an unrefereed format and was then quoted by RFK Jr. in his Senate Hearings for Secretary of Health and Human Services.
In my conversations with Alzheimer scientists, most deplore this book’s modus operandi and conclusions. Most of my U.S. colleagues do not speak up because they are afraid to lose their jobs in this time of DOGE cuts and leadership change at NIH. Others tried to speak up but were shut down by Science. Ditto for The New York Times, which published an opinion article by Piller plainly promoting his upcoming book but rejected a rebuttal submitted by 20 researchers who had devoted their careers to fighting Alzheimer’s disease. Piller is selling books and getting attention on the speaking circuit, but he is not helping people struggling with Alzheimer’s, or scientists trying to stop this disease.
I have consulted for Eisai, Eli Lilly, and Roche on their Alzheimer and Parkinson disease programmes.
References:
Benilova I, Karran E, De Strooper B. The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci. 2012 Jan 29;15(3):349-57. PubMed.
UK Dementia Research Institute@UCL and VIB@KuLeuven
Why Is Science Lending Credibility to an Anti-Science Journalist?
Reading this JAMA editorial, I find myself in full agreement with its central message. The exposure of fraudulent research and the unethical behavior of certain biotech companies is both necessary and commendable. Mr. Piller rightly brings these issues into the public sphere, highlighting practices that should not only be condemned but also held accountable. However, he goes too far when he extrapolates from these cases to accuse an entire field of research, and by extension, thousands of dedicated scientists, of fraudulent behaviour.
The real danger arises when Mr. Piller implies that the drugs currently in development are founded on non-science, weaving a sweeping conspiracy narrative built on selective and biased analyses. Such claims are not only misleading but also deeply harmful to scientific progress and, ultimately, to patients who depend on well-founded research efforts. As scientists, we are no strangers to misinformation—whether from fake news, anti-vaccine movements, or distortions of scientific debate. What is particularly troubling here, however, is that this misinformation is being disseminated by an employee of Science. This, to me, is a critical and deeply concerning issue that deserves as much attention as the misconduct Piller seeks to expose.…More
Why does the journal Science—published by the Association for the Advancement of Science—lend its considerable prestige and authority to anti-science journalist Charles Piller?
Below, I share my emails to Science, and the magazine’s response, when I questioned why they chose to support Mr. Piller and allow him to present himself as a Science journalist. I don’t do this lightly. Emails stay among their respective correspondents for good reason, and publishing the below might infuriate people. Even so, someone has to speak up and inform the public about the other perspectives.
The emails summarize my major concerns with Mr Piller’s approach. Apparently, his freedom of speech at the magazine appears to be an umbrella under which he can promote data misrepresentation and false accusations. My concern is that Science has given Mr. Piller a scientific credibility he does not deserve.
I was informed that the journal's editorial and opinion sections operate independently. Understood. Even so, Mr. Piller exploits his association with Science to gain respectability and blur the line between peer-reviewed research and his rhetoric. This will benefit his book sales but hurt science and people with Alzheimer’s disease. While doing my research on this I was struck by a post from former Science Editor-in-Chief Jeremy Berg, who raised concerns about Mr. Piller’s reporting in a detailed, 77-part critique on Bluesky. It demonstrated that Mr. Piller has a history of distorting the scientific truth to make scientific research suspicious.
Below I paste my email conversations with Science regarding the contributions of Mr. Piller. I find the responses I received deeply worrisome, and I believe it is important that the scientific community gets informed about the way Science thinks these days.
My email, sent 1 February:
Dear Editors of Science,
As a researcher who regularly publishes in Science on Alzheimer's disease, I am writing to express my growing concern over the recent articles by Mr. Charles Piller. These pieces exhibit significant logical fallacies, including "pars pro toto," faulty induction, hasty conclusions, and notably, sample bias—errors that would be unacceptable in a scientific manuscript. While such sensationalism might be expected in popular media, Mr. Piller leverages the esteemed reputation of Science to lend his claims an unwarranted veneer of scientific credibility. He has now extended this platform to publish an astonishing article in The New York Times, accusing the entire field—comprising thousands of dedicated researchers—of scientific fraud. The repercussions are severe: policymakers echo and amplify Mr. Piller's assertions, and patients begin to question the integrity of their physicians.
The crux of the issue with Mr. Piller's publications is his extrapolation from a few confirmed instances of fraud in the expansive field of neurodegenerative research to suggest that all related work is fraudulent. He particularly targets the amyloid hypothesis, yet the studies he cites pertain to α-synuclein (Parkinson's disease), vascular dementia, and a publication that critiques the amyloid hypothesis, proposing an alternative perspective on Alzheimer's disease. The sole paper directly related to the amyloid hypothesis had already been discredited within the field long before any fraudulent activity was uncovered. In a review I authored in 2012, I referred to this work as an "oligomer in need of clothes."
I firmly believe that Science should eschew sensationalism and provide a rigorous, peer-reviewed platform for scientists and journalists aiming to challenge scientific hypotheses. It is deeply troubling that Science, a flagship of the scientific community, has opened its pages to manipulative narratives. Moreover, Science has failed to disclose a significant conflict of interest in publishing this material: the journalist in question seeks to sell stories—books and articles—and it is well-known that sensationalism and gossip sell better than balanced analyses.
Mr. Piller's focus on isolated instances of fraud—which I unequivocally condemn—leads him to claim that billions of dollars have been misallocated in clinical trials and research. For every fraudulent paper, there are 99 others that correct or nuance the findings. Progress in the field has been remarkable and is already translating into benefits for patients. It is intrinsic to scientific progress that false claims are eventually corrected. Allowing Mr. Piller’s sensationalism is causing the field irreparable damage. (…)
I am truly astonished that Science has opened its pages to this type of unscientific narrative.
In conclusion, I urge Science to uphold its commitment to balanced and evidence-based reporting, ensuring that critiques are grounded in comprehensive analysis rather than sensationalism.
Sincerely,
Bart De Strooper
PS I would like to suggest to publish my letter which might demonstrate the willingness of at least the scientific redaction [editor’s note: "redaction’"in the author’s native language means desk/section of a publication] of Science to respect the scientific process and take distance of the anti-science movement that at this moment is spreading rapidly over the world and in the USA in particular.
The response of Science, sent 1 February:
Dr. De Strooper,
Thank you for your note. Our news operation is independent of research. There is a good reason for that, which this situation illustrates—our news department is free to write about our papers and we don’t weigh their criticisms more than any other critic. I am responsible for working with the news editor whenever questions arise on one of our news stories. While Charlie’s stories get a lot of inquiries, we have not had any of the fundamental facts disputed successfully. The fact that we have plenty of papers on the amyloid hypothesis that we stand behind and were proud to publish does not change what news is permitted to cover or confer any obligation on our part to reconcile the two. These ideas about a free press are fundamental to how we operate the magazine—and I dare say there are too few left who adhere to them.
Dennis Selkoe had a Perspective a while back (I remember well because we stood up to a lot of people who wanted it retracted who are on the other side from you when it comes to amyloids) and he was permitted to respond to a letter on it. So we have given a lot of space to this matter.
A lot of people object to the fact that we have an editorially independent news department, but they are providing outstanding coverage of the troubling events going on around the world right now, and especially in the United States.
Charlie’s book is likely to be a big seller. My advice to the amyloid community would be to figure out a proactive story rather than attacking journalists, which has never worked very well.
Thanks again.
[Name withheld]
My reply, sent 2 February, which received no response from Science:
Dear [Name withheld]
Thank you for your response. I appreciate the importance of editorial independence in journalism, and I fully support the role of a free press in scrutinizing scientific research. However, I would like to clarify my position, as I believe my concerns have been misrepresented.
First, I am not part of the "amyloid community," nor am I invested in defending a particular hypothesis (see two abstracts of papers that I published in the peer reviewed literature pasted below). My work is focused on understanding the pathogenesis of Alzheimer’s disease, and my concerns stem from the broader implications of how scientific discourse is being presented to the public.
Second, my objection is not to a journalist's right to report on scientific matters, but rather to the way in which a highly regarded scientific journal is being used as a platform to cast suspicion over an entire field without due balance or critical engagement with the full scope of evidence. While critical journalism is necessary, the manner in which this issue is being framed risks misrepresenting complex scientific debates and damaging public trust in rigorous research. The central issue is that Mr. Piller presents his argument as a scientific debate, framing his viewpoint—and those of a small minority of researchers—as equally weighted against the overwhelming majority of experts in the field. His method follows a familiar pattern: extrapolating from a few confirmed instances of fraud to cast doubt on an entire body of work. This is not rigorous critique; it is a misrepresentation of scientific discourse. The press bears a significant responsibility here, as history has shown the dangers of amplifying fringe scientific positions. A particularly tragic example is the case of HIV/AIDS in the 1980s, when a small group of scientists, led by Peter Duesberg, denied that HIV caused AIDS. Their views were disproportionately amplified in the media, leading to devastating policy decisions—most notably in South Africa, where life-saving AIDS treatments were withheld for years, worsening an already catastrophic epidemic. I note that you have not addressed my specific concerns about the potential consequences of such reporting. With this regard I refer to the point of view as expressed by RFK Jr in the link provided in my previous letter (…), which confirms my worst expectations.
Finally, the assertion that no fundamental facts have been successfully disputed does not eliminate concerns about selective reporting, the omission of counterarguments, or an undue focus on controversy at the expense of constructive scientific discourse. By bringing this matter into the public domain, the journalist has created an inherently unequal situation, where information that should have been handled with due process is now subject to selective public scrutiny and interpretation, resulting in a complete distortion of the truth in the public’s eye. As you say, this will come with a huge financial profit for the journalist.
I fully agree that the field must proactively communicate an evidence-based narrative, and I would be glad to contribute to that discussion. My concern about Mr. Priller’s book would be far less significant were it not for the implicit trust conferred by his association with Science as a journalist.
I would appreciate any suggestions you may have on how to navigate this situation as it continues to unfold. If we are not given the opportunity to respond to the destructive representation of a whole field of medical research as made by Mr. Piller and some of our colleagues before the same audience as they received, how can we meaningfully contribute to a debate that has now escalated into a broader political discussion?
Best regards,
Bart
The Cellular Phase of Alzheimer's Disease (2016)
Abstract
The amyloid hypothesis for Alzheimer's disease (AD) posits a neuron-centric, linear cascade initiated by Aβ and leading to dementia. This direct causality is incompatible with clinical observations. We review evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature. The field must incorporate this holistic view and take advantage of advances in single-cell approaches to resolve the critical junctures at which perturbations initially amenable to compensatory feedback transform into irreversible, progressive neurodegeneration.
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes (2012)
Abstract
The "toxic Aβ oligomer" hypothesis has attracted considerable attention among Alzheimer's disease researchers as a way of resolving the lack of correlation between deposited amyloid-β (Aβ) in amyloid plaques—in terms of both amount and location—and cognitive impairment or neurodegeneration. However, the lack of a common, agreed-upon experimental description of the toxic Aβ oligomer makes interpretation and direct comparison of data between different research groups impossible. Here we critically review the evidence supporting toxic Aβ oligomers as drivers of neurodegeneration and make some suggestions that might facilitate progress in this complex field.
Indiana University
The letter below was sent to the NYT, which declined to publish it. It was posted on LinkedIn and X, and I am reposting it here on behalf of my 24 co-signatories.
"Mr. Piller shines a spotlight on a handful of unethical individuals among thousands of exceptional researchers whose rigorous work has led to many important discoveries in Alzheimer’s disease. As in all fields, there have been a few unscrupulous or careless researchers, and it is disingenuous to broadly discredit scientific advances based on their actions. In science, theories about the causes of disease and the development of treatments are never the work of a single person. While individuals can propose novel ideas, the field must reproduce and carefully test these ideas. When theories are disproven, the field moves on, and when discoveries are proven correct, the field continues to build on them and push the science forward.…More
"Thanks to critical investments by the NIH, biotech, and pharma, we now have the first FDA-approved disease slowing treatments, and blood tests for diagnosing Alzheimer’s disease. We are also making progress in developing treatments that target elements of the disease beyond amyloid plaques. These advances are the result of decades of collaborative research from thousands of scientists around the globe. Mr. Piller devalues these important advancements, and by doing so does a disservice to the millions of Alzheimer’s patients, research participants, and their families."
Paul Aisen, M.D., Keck School of Medicine of the University of Southern California, Los Angeles, CA
Liana G. Apostolova, M.D., Indiana University School of Medicine, Indianapolis, IN
Laura D. Baker, Ph.D., Wake Forest University School of Medicine, Winston Salem, NC
Karen L. Bell, M.D., Columbia University Irving Medical Center, New York, NY
Suzanne Craft, Ph.D., Wake Forest University School of Medicine, Winston Salem, NC
Jeffrey L. Cummings, M.D., University of Nevada, Las Vegas, Las Vegas, NV
Bart De Strooper, M.D., Ph.D., University College London, UK, University of Leuven, Belgium
Lea T. Grinberg, M.D., Ph.D., University of California, San Francisco, San Francisco, CA
David M. Holtzman, M.D., Washington University School of Medicine, Saint Louis, MO
Lee Jennings, M.D., Oklahoma University, Oklahoma City, OK
David S. Knopman, M.D., Mayo Clinic, Rochester, MN
Cynthia A. Lemere, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Allan Levey, M.D., Ph.D., Emory University, Atlanta, GA
Oscar L. Lopez, M.D., FAAN, University of Pittsburgh Medical Center, Pittsburgh, PA
Ronald C. Petersen, M.D., Ph.D., Mayo Clinic, Rochester, MN
Gil D. Rabinovici, M.D., University of California, San Francisco, San Francisco, CA
Rema Raman, Ph.D., Keck School of Medicine at the University of Southern California, Los Angeles, CA
Eric M. Reiman, M.D., Banner Health, Phoenix, AZ
Mary Sano, Ph.D., Mount Sinai School of Medicine, New York, NY
Eric Siemers, M.D., Accumen Pharmaceuticals, Carmel, IN
Dennis J. Selkoe, M.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Malú Gámez Tansey, Ph.D., Indiana University School of Medicine, Indianapolis, IN
Chris H. van Dyck, M.D., Yale School of Medicine, New Haven, CT
Donna M. Wilcock, Ph.D., Indiana University School of Medicine, Indianapolis, IN
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