How Doctored Science Infected Alzheimer’s Research

Atria/One Signal Publishers

More than 120 years ago, in November 1901, German Dr. Alois Alzheimer took on a patient—a 51-year-old woman with “presenile dementia” who’d become paranoid, lost her sense of self, and shouted at neighbors. When she died, the doctor conducted an autopsy, finding in her brain two suspicious proteins: sticky plaques between her brain cells and tangled fibers within them, as science journalist Charles Piller writes in his new book, Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. The disease, named after Alzheimer, would be defined by those two proteins, along with the presence of dementia, Piller explains. “That was Alzheimer’s disease.”

In the early 1900s, Piller notes, people often weren’t living long enough to develop dementia, so decades went by without much research on the illness. As lifespans grew, so did scientific interest in the causes of cognitive decline. In the 1990s, a hypothesis emerged that amyloid proteins—including the sticky plaques—drove the brain to deteriorate, ultimately causing dementia. “It was widely accepted because it made so much sense,” Piller tells me over Zoom, “going back to the genesis of the definition of the disease.” The proof was in the brain tissue.

In the years since, medical research funders, including the National Institutes of Health (NIH), put billions of dollars into studies based on the hypothesis. And while it remains the leading theory of the cause of Alzheimer’s, fractures in its foundation have started to emerge. Many people without dementia die with lots of these proteins in their brains, Piller says. And therapies specifically designed to remove the proteins haven’t been able to stop cognitive decline, let alone reverse it. Skeptics of the amyloid hypothesis began to emerge. (Many of these skeptics, according to Piller, believe amyloid proteins may be involved in the disease. “But there’s a difference between having something to do with it and having everything to do with it,” he says.)

Then came a bombshell. In a 2022 investigation published in Science magazine, Piller and Vanderbilt neuroscientist-turned-whistleblower Matthew Schrag uncovered evidence of apparent image tampering in about 20 journal articles by University of Minnesota neuroscientist Sylvain Lesné, including one influential 2006 Nature paper that seemed to provide evidence for the amyloid hypothesis—and a key foundation for hundreds of follow-up studies because it injected new confidence in the hypothesis. The investigation, as I wrote at the time, rocked the research world. Last year, the Nature paper was retracted. (Shortly beforehand, one of the study’s senior authors said on research chat site PubPeer that the images had been manipulated without her knowledge, but argued that it “did not change the conclusions of the experiments.” Lesné did not directly respond to a request for comment from Mother Jones. Read my interview with Piller about his Science investigation here.)

With the help of a team of “image sleuths,” including Schrag, Piller expanded his investigation, finding evidence of possible misconduct in hundreds more neuroscience papers—including, to Schrag’s surprise and dismay, work by one of Schrag’s mentors.

It’s a haunting, important book. (I inhaled it cover to cover over a weekend.) But at the same time, it arrived at something of an uneasy time for science—just weeks into President Donald Trump’s second term, amid what research advocates have described as a “war” on science, with funding cuts and job terminations across the federal government. At the NIH, the administration paused (and later restarted) grant reviews and reportedly laid off some 10 percent of the Center for Alzheimer’s and Related Dementias, including incoming Acting Director Kendall Van Keuren-Jensen. These cuts, “if sustained,” Piller says, would be “catastrophic to US biomedical research.” While the NIH may need to “up its game” in preventing or detecting image doctoring, he says, “slashing the agency’s budget and firing experts who are the keepers of all-important institutional memory is exactly the wrong way to attain those goals.”

I recently spoke with Piller about how writing the book changed his own perspective on science, whether the amyloid hypothesis’ monopoly on Alzheimer’s research can be broken, and what highlighting one of the field’s darkest episodes means for trust in medical institutions at a time when they’ve come increasingly under attack.

Here’s a lightly edited and condensed version of our conversation.

For me, your book—all the misconduct you’ve uncovered—was deeply disturbing. How did you cope while writing it?

Honestly, yes, there are a lot of discouraging things I reported on for the book. What really made me feel like I could continue to do this work, and also feel a sense of hope and maybe even some optimism, is that there is now a small army of people out there who are aggressively going after apparently doctored images. It’s an example of how crowdsourcing has created a force that’s requiring institutional authorities of science to take this more seriously and to do their own due diligence in a more serious-minded way.

I’m also inspired by the fact that there have been a lot of new ideas about possible treatments and maybe someday a cure for Alzheimer’s disease percolating up, notwithstanding the dominance of certain ideas in the field, including the amyloid hypothesis. Science is vast. You can’t repress those ideas completely, because people are too creative and too thoughtful.

How do you feel about the book coming during this period of the Trump administration? Last time we spoke, for instance, you talked about how Tucker Carlson ran a segment about your reporting and used it as an opportunity to critique science at large. Are you concerned your book will add fuel to the fire?

Our work can always be misused by people who are behaving in disingenuous ways or trying to exploit it for political purposes. Of course I’m troubled by that, but I have no alternative but to do the reporting that I think is important.

It would be a disservice and a betrayal, not just to the profession, but to Alzheimer’s patients and their families, if I were not to expose things that I think are being done, not just improperly but dishonestly, that have harmed progress toward a cure for the disease. If I stop doing that for fear that it might be misused, then I might as well stop being a journalist.

As you write in the book, Sylvain Lesné is the interview you “wanted most but would never get.” If you had the chance, what would you ask him?

What I want to know is the same thing that a lot of people want to know when they think about these issues of misconduct: Why?

I’ve been thinking about this for years. I have my own thoughts about what happens for people in these circumstances. I can tell you what I think.

Yes! Please tell us. Why would people, in general, do this?

I think what happens a lot of the time is that there’s a kind of slippery slope, where it starts out, where a person might do something like what they call “beautification” of a scientific image. It’s making it look a little better, clipping out a certain edge of it that’s not very visually or aesthetically appealing, to give it more curb appeal for journal editors. Even though this might be frowned upon in scientific publishing, people often look the other way.

Then you may get a situation where you’re looking for a particular result based on your experimental hypothesis and you don’t quite get it. You get some weak evidence of something, but not quite what you thought you were hoping for. And the scientist might say to him or herself, I’m just going to sharpen it up a little bit, because I know there’s something really true there. And then they submit it. It’s published. And because there’s so much complacency within journals, no one would have necessarily noticed that it happened. When you get away with it like that, I think some people might tend to go to the next step, which is, I didn’t quite get the result I wanted, but I feel so sure of my ideas that I’m going to just create an image that really reflects those ideas, because I know future experiments are going to prove this out. Obviously, that’s misconduct.

There are also people who are just, frankly, dishonest. They’re exploiting opportunities for fame, fortune, prestige in the field by generating false results that are provocative and would make a name for themselves and get away with it.

One of the big “WTF” moments for readers of your book is the section where one of your primary sources, whistleblower Matthew Schrag, is informed that one of his own papers has been flagged for possible misconduct. He discovers his former mentor allegedly doctored images. Was there ever a point when your view of Schrag changed?

The episode you’re referring to was heartbreaking for [Schrag]. This was not just a guy he worked with, but it was his first mentor in science when he was an undergraduate. He became a dear friend, someone who he trusted completely and who he respected deeply.

What Schrag did cemented my view of his integrity like perhaps nothing else could. When it was brought to his attention that two or three of his own papers from his undergraduate days were being called into question for possible image doctoring, he not only looked closely at those papers, but he took it upon himself to investigate a wide swath of the whole body of work of his mentor to determine whether these were just aberrations in what had been a very honorable and successful career in science, or if there was a pattern of image manipulation that was shot through his mentor’s body of work.

Much to his grief and much to his surprise, it was the latter. His own mentor had engaged in a pattern of decades of apparent image manipulation misconduct. And he confronted his mentor about this, and it was one of the most difficult conversations of his life. In my view, that was a reflection of his integrity and trustworthiness as a source. [Editor’s note: As Piller reports, an investigation by Schrag’s former university, the University of North Dakota, determined that Schrag’s mentor Othman Ghribi had committed research misconduct in a 2008 paper. Ghribi did not respond to a request for comment from Mother Jones.]

Many of the researchers you write about, supporters of the amyloid hypothesis, seem to have stuck behind it, almost like a religion. Some scientists even seemed to look for results that fit the hypothesis. That just goes against everything that science is about. Why do you think that’s happened?

Part of the reason is that there’s an enormous amount of sunk costs in the scientific community, both by the government and by drug companies. And when billions and billions of dollars have been spent on an idea, it’s so hard to give it up, even if there are cracks in the logic behind it.

The second thing is a lot of really prestigious people have spent their entire careers trying to prove this out. And if it’s not true, if it’s not the explanation for this disease that they have been working for, literally, for decades to try to demonstrate, then it’s a big hit on their scientific legacy. That’s a pretty hard thing for people to give up scientifically. Even if you’re a great scientist, it’s tough to come to that realization.

Yes, I wondered if “arrogance” was in the book’s subhead for that reason. Has doing this reporting made you think differently about science—its flaws or just how it works?

It’s caused me to temper my sense of trust in the way the institutional authorities of science have managed their due diligence on science. When I say the “institutional authorities,” I mean journals, universities, federal funders like NIH, and federal regulators like [the Food and Drug Administration]. I’ve grown more skeptical that they have been managing this in a competent way.

And it’s not to say they’re doing a terrible job. I think we are incredibly lucky in our country to have really excellent institutional authorities of science. NIH [funding] has resulted in an enormous number of important breakthroughs that we all benefit from. And regulators like FDA, for all of its flaws, have also been able to help produce a drug supply that is of high quality, generally.

[But] there has been an enormous amount of complacency and carelessness that I would associate with the journals, the funders, the regulators, and the universities. They haven’t done sufficient due diligence to understand whether the work that they’re reviewing might have doctored images and therefore doctored data within them.

So these institutions of science really need to up their game. They need, on their own volition, to be more vigilant, to be more careful, and to just basically be better at monitoring and policing these kinds of problems in their realms. And if they don’t, then the anti-science forces, they’re going to do it for the institutional authorities of science. And it’s not going to be pretty. It’s going to be destructive.

What impact do you hope the book has?

I think it’s an opportunity to reinvigorate thinking in the [Alzheimer’s] field so that alternative ideas to the amyloid hypothesis might be able to gain more interest and, possibly, funding.

The second thing is that I really would like this book to be an opportunity for the scientific community to take a good, hard look in the mirror and try to implement better practices and better support for people who are challenging research that has dubious elements to it.

It’s not that the scientific community is so fatally flawed. It’s just saying that deference to these august scientists and their thinking, and a complacency on the part of journals and funders, has led to a bad situation in science where the public is challenging and questioning whether to believe in science.

Anything else you’d want readers to take away from the book?

I want to leave people with understanding that there’s a lot of hopefulness in the field.

There are studies underway involving the GLP-1 inhibitors like weight-loss drug Wegovy. There’s some evidence that they might be useful in slowing cognitive decline or possibly even some preventive effects in Alzheimer’s research. There will be more information from those trials by next year. There’s also work being done on the “infection hypothesis” of the disease, which holds the idea that certain viral infections, like the herpes virus latently residing in the brain, could be a factor in Alzheimer’s disease.

And finally, I try to emphasize that we as individuals have agency in our lives. We know that risk factors like high blood pressure, high cholesterol levels, unhealthy diets, sedentary lifestyles—those are all things that we have some degree of control over in our lives. By just paying attention to that and living our best lives, there’s a chance that we can forestall some of the worst effects of this disease. We should not give up all hope and think it’s just a matter of fate.