Plain English with Derek Thompson - Fraud, Scandal, and Failure in the Fight Against Alzheimer's Disease

Episode Date: February 11, 2025

Why is it so hard to find a cure for Alzheimer’s? A simple answer is that the brain and its disorders are complicated. But as today’s guest, Charles Piller, writes, there’s another, more sinister factor at play. His new book, 'Doctored,' traces an incredible, true story of fraud, arrogance, and tragedy in the quest to cure Alzheimer’s. In the last few years, some of the most famous and revered neuroscientists in America have been accused of doctoring images in research related to Alzheimer’s and neuroscience—even as they raised tens of millions of dollars in funding based on this doctored science and set up clinical trials for thousands of patients based on these manipulated results. At the same time, a silent conspiracy of groupthink starved this field of research of fresh ideas, with catastrophic consequences. Piller explains how he broke the story of what might be this century's biggest scandal in American medical science. If you have questions, observations, or ideas for future episodes, email us at [e-mail]. Host: Derek Thompson Guest: Charles Piller Producer: Devon Baroldi Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Today, the biggest scandal in medical science. In 2021, the world seemed to be on the cusp of a historic breakthrough in neuroscience. A biotech firm called Casava announced that they had invented a drug that could reverse one of the worst and most mysterious ailments we know, Alzheimer's disease, afflicting nearly 7 million Americans, Alzheimer's, and other forms of advanced dementia, are not just an enormous challenge for patients, robbing them of their memory, their identity. They are a psychic tax on caregivers and a financial burden. In 2023, citizens spent $350 billion in private spending caring for patients of dementia. one-third of one trillion dollars.

But now, in 2021, it seemed we were finally on the brink of a cure. The breakthrough drug was known as Simufulum. It worked by disrupting the accumulation of a specific protein in the brain called amyloid beta, which seemed related to the progression of Alzheimer's. Patients on the drug reportedly saw their memory improve after just one month. Other trials showed that patients' memory and anxiety improved by 10%, and their cognitive test scores soared after just nine months. The market responded with jubilation, and Kasava's market valuation rocketed up by a factor of nearly $300 to $5 billion. Some of the achievements of Kasava seemed downright spooky.

One of the scientists working on the drug, Hu Yan Wang, claimed to have used Simulam, to bring long-dead brain tissue back to life. When he dosed frozen dead brains with the drug, his images showed the brains suddenly transmitting chemical signals between nerve cells. The paper, with this spooky, almost zombie claim, would go on to be cited almost 2,000 times. So here we had the most extraordinary thing, a brand-new drug with amazing potential to reverse Alzheimer's and even bring dead brain tissue back to life. But at the very moment that some euphalome appeared to be a miraculous drug, the downfall began. Scientists questioned the data.

In particular, they worry that some of the imaging, supposedly proving the drug's effectiveness, was faked. Within three years, the entire project would crash the ground. The drug failed in clinical trials. The company went under investigation by the SEC. That zombie brain paper would be under a separate investigation by the Justice Department. An elite scientist, Wong, would be charged by the DOJ with fraud. This Icarus story of a miracle drug might sound like enough of a tragedy, but it's actually just the tip of the iceberg of a much deeper and more troubling pattern of fraud

throughout Alzheimer's research, a scandal that was uncovered by several intrepid scientists and the journalist Charles Pillar. In just the last few years, several of the most famous and revealed, Neuroscientists in America have been plausibly accused of doctoring images and research related to Alzheimer's, even as they raised tens of millions of dollars in funding based on that doctorate science, and even set up clinical trials for thousands of patients based on science proved with manipulated results. Some of these individuals have been fired or put on leave for their participation in this scandal. The president, former president of Stanford University,

Marc Tessier Levine, a global leader in research on brain circuitry and Alzheimer's, resigned in 2023 after a student journalist proved that he, like Wong, had altered numerous images in his research. When people wonder why it's so hard to find a cure for Alzheimer's, the convenient and somewhat true answer is that the brain is complicated. Neuroscience is complicated. But as today's guest, Charles Pillar writes, there is another more sinister factor at play. His book, Doctored, traces the fraud, the arrogance,

and the tragedy in the quest to cure Alzheimer's. Before we continue, I want to acknowledge that I am fully aware of the moment that this podcast is dropping into. I know there are major questions about whether the U.S. is prepared to sustain or cut our level of federal scientific funding. I believe that federal funding on science is one of the most important and best things we do as a country. There is practically no medical breakthrough

in the last 30, 50, even 60 years that does not emerge from federal research grants. But I also think that loving science, as I do, means seeing it clearly, warts and all, not turning a blind eye to its failures and its shortcomings. If you love science, you should want to see science done well. And that means paying wide-eyed attention to what it costs us when scientists fail us. I'm Derek Thompson.

This is plain English. Charles Pillar, welcome with the show. Thanks so much for having me. You write in your book that for decades, Alzheimer's research, was shaped by the dominance of a single theory, a single protein theory, called the amyloid hypothesis, and that in the last few years and even decades, nearly every drug approved for Alzheimer's dementia in the United States is based on this theory. What is the amyloid hypothesis? Okay. I'm going to wind us back all the way back to 1906, just briefly, which was the date of the kind of quote-unquote discovery.

of the disease by Alzheimer, a German scientist, namesake of the disease. And what he was as a pathologist and a clinician. So he's treating a patient who had dementia and this person ultimately died and he did an autopsy on her brain. And he saw in the brain copious amounts of amyloid plaques. And this is amyloid is a type of protein.

And the sticky plaques are the sort of characteristic description of what scientists see characteristic of this disease. And also another protein that's called tau that is the tangles within nerve cells. So you have the plaques outside of the nerve cells. And also it would later learned that other forms of amyloid protein were soluble forms of the protein were floating around in the fluid that bathes the brain. And also these tangles. And Alzheimer said basically this combination of factors, plaques, tangles, and dementia. That's the disease. And it caught on. It was named after him. But for decades, there wasn't much progress or even enough interest in the disease

to take a deep dive into what might be going on biochemically, partly because it's a pure demographic explanation. There weren't that many people living to old age, the age that Alzheimer's normally has this age of onset. And consequently, it just wasn't that big a medical problem. But advances in other medical fields drove demographics differently. People started living longer. Huge population of older people began to be dominant in the population compared to their earlier numbers. And a lot of those people were getting this disease. So suddenly had a gigantic confusion of interest in not just Alzheimer's, but in the original thinking about the disease, plaques, tangles, dementia, the amyloid idea. And so in the early 90s, this was conceptualized

into something called the amyloid cascade hypothesis by certain scientists. And essentially, it's very simple. It works this way that amyloid plaques and other forms of amyloid protein start a cascade of biochemical effects in the brain that eventually, leads to dementia. So you brought us up with the history of Alzheimer's research from the early 20th century into the late 20th century. Between the 1990s and today, how did the amyloid hypothesis take over Alzheimer's research and drug development? Well, there are a few reasons. One is, let's be fair to the scientists who developed this hypothesis, this made incredible amount of sense. You look inside the brains of the brain.

of people with Alzheimer's disease and you see copious amounts of amyloid plaques, other forms of amyloid, and you see these tangles inside their nerve cells. So of course, there was a lot of interest in this. It was logical. And people pretty much jumped on that bandwagon when they started to understand that this combination of factors was so logical. Subsequent to this hypothesis being framed out by scientists, a flood of money came into the field. The National Institutes of health began to send millions, hundreds of millions of dollars in the direction of exploring whether amyloid proteins really were the source of this and how best to attack that problem. And so because of all this funding, because of all this scientific interest, it grabbed a

huge amount of mind share in the scientific community. There were always alternative explanations for Alzheimer's disease, always ideas that were contrary to this lockstep approach with the amylite hypothesis, but they were, in essence, crowded out, not just because the hypothesis made some sense, but because powerful figures within the scientific community were favoring that hypothesis and opposing spending a lot of money on other kinds of research associated with the disease. I can see how a theory creates a target zone for funding. Like, if nobody has any idea what indicates Alzheimer's, then there's no attack plan, and

there's no theory for investment. It's the theory that creates the target zone for attracting funding. But if the deposit of amyloid proteins is an indication of Alzheimer's, what's wrong with the amyloid hypothesis? Well, there are a couple important contradictions associated with the hypothesis. One is that amyloid plaques are present, even tangles are present, in the brains of many older people who die without experiencing any symptoms of Alzheimer's. So that's been a nagging contradiction that skeptics of the amyloid hypothesis have often raised as a reason to think more broadly.

That's number one. Number two is what happened after this influx of funds. So in the 90s and early 2000s, enormous amount of experimentation was going on. And there were even clinical trials of drugs that attack amyloids, pull them out of the brain. Even a vaccine was developed that did the same thing. And these were very successful at removing amyloid plaques and other types of amyloid proteins from the brain. But they were very unsuccessful in having any benefit for Alzheimer's patients. In other words, cognitive decline continued.

And people did not have any benefits. And some experiments showed hazards that could be very dangerous for the patients. All right, we're moving through history. The amyloid hypothesis is gathering steam, especially since the 1990s. But there are still some doubts about whether removing amyloid plaque from people's brains actually slows or reverses the disease's progression. And this brings us finally to 2006 when a paper comes out that seems to change the game. What is this paper and what does it find? So this paper was published in the eminent scientific journal nature.

And it was very important timing because in 2006, there was a lot of discouragement and skepticism rising about the amyloid hypothesis. That's because the failures of those drugs that I mentioned earlier were beginning to lead to a bit of discouragement among people who had been spending much of their career slaving a way to try to find a solution to Alzheimer's using that set of ideas. So this was a very clever experiment. It was developed by scientists at the University of Minnesota. And what they did is they used a mouse that is able to produce copious amounts of amylate proteins that deposit in the mouse's brain. And they pulled those proteins out of the brain and isolated one specific protein that they named amyloid beta star 56. Their star amyloid protein, kind of a catchy name, helped them. gain attention and mind sharing the scientific community. Then they took this protein and injected it

into rats. And they described an experiment where the rats then showed symptoms of memory loss that they compared to the memory loss symptoms of Alzheimer's disease. So what you have for the first time is a specific substance that seems to have a cause and effect relationship with the disease. And it was a specific amylate protein. A type of amylate protein is the kind that's full. around in the cerebrospinal fluid that baths the brain, a little bit different from the plaques, but still the same family of protein. So this was very, very important. It reinvigorated the field. A lot of scientists wrote about this and saying that this is what we've been looking for. This was the kind of experiment that shows that we're on the right path, that we can continue

with our work on amyloid proteins, with the confidence that we know we're headed in the right direction. a gigantic influx of funding came through from the federal National Institutes of Health and from private sources and drug development by drug companies. We're talking ultimately billions of dollars over the years. And this was very, very important because it essentially rescued the Amelite hypothesis. This study was cited thousands of times. It became one of the most important and cited studies in Alzheimer's research for a period of 16 years until 2022. All right. I think it's finally time to bring Charles Pillar into the story. When did you, Charles, first get wind that something was amiss in the field of Alzheimer's research or

Casava sciences specifically? So the genesis of this whole big project really was that moment when I was speaking on the phone with a particular image sleuth, who's a neuroscientist at Vanderbilt University, name of Matthew Shrag. The two of us were talking about some of his findings associated with this 2006 study. What he was seeing was evidence that a lot of the data in the study in these so-called Western blots

appeared to have been Photoshopped. Photoshopped. That's right. So the images were changed to reflect the experimental hypothesis. So it appeared. And just to brief aside, Charles, feel free to get a bit technical here.

I just want us on the same page. When we're talking about brain imaging for neurological disorders like Alzheimer's, what are we talking about? What are you looking at? Well, what I'm talking about is in Alzheimer's science, there are really two most important types of images that are used to display experimental results.

and how these are displayed can have a big bearing on whether people are well supported in their beliefs and their assumptions about their work. And in this case, whether there was reason to believe that this drug, simupholum from Kazaba Sciences, is one that had a lot of potential and should really be explored fully and tested in people. And these images are two kinds, really. One is something called micrographs, which are highly magnified images. photographs of usually brain tissue. And they show all the different small features,

including nerve cells, et cetera. And the other is something called Western Blots. And each of those can be manipulated in different ways. So just to take the first one, micrographs, they can be copied and pasted in different ways. Sections can be moved around or obscured. So the idea being that if you accentuate a certain thing in a photographic image,

or you remove something, you can change the results of an experiment. These images are, in fact, the data from the experiment itself. And then the second kind, Western Blots, this is a way of photographically displaying types of proteins in a tissue sample or in a blood sample. And it goes through a device that separates these proteins by their molecular weight. and then it displays them in stacked bands that look like kind of almost a ladder-like configuration of mis-shape and ladder steps. And when you look at these, you can see the concentration and type of specific proteins in a sample. It's very important in Alzheimer's disease, which is based largely on the idea that certain proteins drive the disease. And so if you take these bands and you change their shape or you move them from one place to another

or you remove them with an erasure tool in Photoshop, you can create data that corresponds to the ideas that you're postulating in your experiment, whether or not the actual data reflects those results. Thank you for that. And back to the story, you're talking to this scientist, Matthew Schrag, about the possible discovery of photoshopped images in a landmark paper that has been held up as a key pillar of the amyloid hypothesis for Alzheimer's. What happens next? We were both a little bit stunned thinking about this together at that moment. This was in January of 2022 after he and I had been

talking for a month or so about these matters. And what Matthew Shragge and I were both stunned about is that we knew that this was a seminal study in the history of Alzheimer's disease. In a way symbolic of a lot of the challenges and triumphs of the amyloid hypothesis in the scientific field. And so we knew that if this experiment had been faked, essentially, and again, this was at a point where it appeared that the images had been doctored, but I hadn't done my own due diligence yet. Both of us were saying this appeared to be the case, but more work needed to be done to find out for sure. So that was months of reporting that followed.

And months of me vetting Shrag's findings about the images and also vetting his assumptions about the importance of this study with some of the top experts in Alzheimer's disease. So this was the reporting process I went through my own due diligence as an investigative reporter where, of course I had to do that. Of course, I couldn't just take what he said on faith. So what I did finally was to write an article that showed that his assumptions, his work, his investigation of those images seem to be very valid according to those two types of experts, forensic image analysts and experts in Alzheimer's disease.

And that story is published in science, and it was something that really disturbed the field dramatically. So nature, esteemed journal of scientific research, reads your reporting, how did they respond? What is the current status of that landmark 2006 paper. Sure. So just to be clear, of course, I submitted all of the findings to nature well in advance. And in fact, they had been aware of it for months prior to that because Matthew Schrague gave it to him. He wants to make sure that he follows a prescribed method for trying to correct the

scientific record if necessary. And what nature did is sat on it for a long time. They started an investigation where they consulted with the scientists who are involved in the experiment. they consulted with the University of Minnesota. That was the university where the experiment was primarily conducted. And lo and behold, two years later, the paper was retracted. In June 2024, nature retracts this famous paper for image doctrine. And you can see it now, actually, if you search for the paper. It's still on the Nature website, but the headline begins with the all-caps words,

retracted article. And just days after that, Hu Yan Wang, the rejuven. researcher, the scientist at Casava Science, he's indicted on charges alleging research fraud. So Charles, how deep does this scandal go? Well, let me give you two examples, Derek, that I think capture the severity of this problem. The fraud goes very deep, and I'm going to talk a little bit about what it does show in it, when it doesn't show later on. But I want to say that it's a big problem.

And these two examples, I think, show how deeply it goes in important areas. One is a guy by the name of Bereslov Slocovic, who is a scientist at the University of Southern California. And the story that I wrote about him, and this was based on the collaborative efforts of four forensic image analysts, they sometimes are referred to as image sleuths, who, some of whom had great scientific expertise in neuroscience, not all, though. And Zlakovich was and is one of the world's most influential scientists in issues related to the blood-brain barrier. This is a protective mechanism in the brain to prevent basically from bad stuff getting into the brain and harming the brain. And he was always very interested in how that might be associated with neurodegenerative disorders like Alzheimer's and Parkinson's disease. And he had done many studies about this over the years. Well, the team of image sleuths that I worked with, which included Matthew Schrague from Vanderbilt University and others, looked very closely at the research that Zlakovich was engaged in for many years and found that in study after study, there were apparent problems that pointed to possible image manipulation.

And so just like I did for the story of this 2006 Nature paper, I did a thorough look at the image. associated with that. Then I did my due diligence. I had other people weigh in on whether the findings seem valid. I had top scientists in the field. Look at this. And honestly, they were stunned by it, stunned by how terrible the apparent effects of this would be. Just to give you an example, this scientist, Lakovich, was at the time, his work was used as a basis for a major stroke trial. So this wasn't even Alzheimer's disease. It extended to stroke and other ailments. And this trial, which was going to involve a couple thousand patients, was about to kick off with a promised $30 million in funding by NIH. And so when my story

appeared in science and revealed that there was a parent image doctrine directly associated with the underlying studies that led to the testing of a new drug from a company that Zlakovich had financial interest in for treating stroke, the agent. immediately stepped in and shut down the trial three days after the story appeared. And that's a situation where the evidence was so disturbing and so incontrovertible that the agency felt that it had to act. That drug now has been taken off its pace for a clinical trial for stroke. But it was an example of this trusted authority in the field. Someone who was literally one of the top figures in Alzheimer's research was found to have been apparently

engaging in image doctoring or it was at least coming out of his lab for many, many years. So that's an example number one. I think it's important to raise one other example in this context. This one is, to me, truly mind-boggling. It's perhaps the most egregious case. This is a guy by the name of Elizer Moslia, who is a scientist at the National Institutes of Health. until recently he was the director of the division of neuroscience at NIH. And so for context, listeners should understand that this is the agency that funds most of the important neuroscience research in the country, basic science that leads to drug development and even funds some drug development studies as well. And this guy was at the top of this.

He was at the top of the power structure to decide on what to fund, to advise the country on what would be worth, while. And in addition, he had been for decades one of the leading scientists in Parkinson's and Alzheimer's disease with immense productivity coming out of his lab at UC San Diego before he became the director of this division at NIH. And the scientists that were, the scientists and the image sleuths that were in collaborating with me to try to understand better the extent of problems within Alzheimer's disease, we latched on to mauslia in part because there were breadcrumbs, you might say, in the scientific record there might be something amiss. And he was important. So that were, those were important reasons to get a close look at what he was doing, going back in history,

going back 25 years. I should mention that the people involved in the examination of his studies were Matthew Schrag, I mentioned earlier, who was working completely outside of his day job at Vanderbilt, just on his own freelance at image integrity work. A guy by the name of Patrick, Kevin Patrick, who is someone who is a non-scientist, but is very adept at software and can try to understand how images might have been manipulated. A woman by the name of Elizabeth Bick,

who's a premier image integrity expert. And last, a scientist, Mu Yang, who is a biologist at Columbia University, who took the lead role in examining the bulk of the studies by Moslia for the work that was done for my book. So what did they find? They found literally 132 studies that appeared to have been based on image manipulation. They developed a 300-page dossier on these studies. It is a pretty stunning body of work.

It's not that they couldn't find other problems. in his work. They stopped at 300 pages because they thought, okay, we've made our point. So this is a guy, again, top of the power structure, leading not just top of the power structure, but his work had been cited thousands of times in the scientific literature, 18,000 citations to studies within these 132 that appeared to be based on tainted images. It's absolutely shocking, Charles. And we're talking about leading neuroscientists, faking evidence, and putting thousands of people in clinical trials based on that faked evidence. We're talking about the director of the Division of Neuroscience at NIH.

I mean, we haven't even mentioned the fact that the president of Stanford University, Mark Tessier Levine, another global leader in research on brain circuitry and Alzheimer's, was also forced to step down because of is his own? image faking or evidence that he was faking images himself. Is this the most expensive, most widespread example of catastrophic research fraud in the history of modern science? Does anything come close to this? That is a terrific question, Derek. I'm not sure I can answer it, but what I can say is that, fortunately, when I presented all of this evidence, obviously as a reporter what I'm going to do in advance of writing a story about this is I'm going to present it to the subject of the story. And unfortunately, Moslia did not respond to any of my request for comment. The National Institutes of Health, however, on the day my story appeared in science about this,

and it's also, of course, detailed in my book doctored, on the day the story appeared, they announced that Moslia is no longer going to be the head of that division because they had investigated two, exactly two, two, of his papers and found scientific misconduct, not the 132 that I had submitted to them earlier. So that was the outcome of that, which I think is beneficial. Let me see if I can put this to a little bit of context scientifically. So Alzheimer's is a special case for certain reasons, but it's not completely unique in the regard to image doctoring or misconduct.

So misconduct takes place not just in every scientific field, but in every walk of life. Let's face it, people are people. In any population, people, a certain number are going to cut corners. They're going to play to their own financial or professional advantage improperly. They might even commit fraud. The vast, vast majority of people in this field are honest and deeply determined to do the best work to solve this problem of Alzheimer's. There's no question about that. But a few people in high positions, a few people with carefully placed but unfortunately untruthful

work can have an influence, a deleterious influence that skews thinking in the field. And I think this is what happened with Moslia, with Zalakovich, and with lots of others that are detailed in a book. We looked, when I say we, look, this is my book. I'm speaking for myself. But I was very fortunate to have the help of this team of image sluice who looked at 46 scientists in the Alzheimer's field, including quite a few important leading scientists, and examining many hundreds of papers and found about 600 papers that were based on apparently doctored science. Charles, how much do you think this scandal has cost us in terms of progress on Alzheimer's research?

So I'm going to take one step back to provide that context. There are other diseases, other important diseases like cancer and heart disease for which there has been faked studies, for which there have been doctored images. This is something that happens in science. That small percentage always happens. But why have the death rates from these other diseases continue to go down? Well, the death rates from Alzheimer's disease have gone in the opposite. direction. Well, it's for a few reasons. One is that the brain and the mind are incredibly hard

medical problems to attack. It's so difficult to solve this disease. And so I don't want to make it sound like somehow this has derailed everything. It's just a tough problem. Second, the domination of one way of looking at the disease, the amylite hypothesis that has had most of the mind share of the field for many, many years, that has, in effect, crowded out other kinds of thinking about disease, that has effectively forced a lot of scientists to conform to the conventional wisdom. The combination of that, the difficulty of the problem, and some small amount of fake science that has skewed thinking in the field, that is combined for a very tragic outcome. that is very little progress, concrete progress in curing the disease.

We're talking here about two different ideas that can overlap but are fundamentally very distinct, which is fraud on the one hand and group think on the other hand. You can have a lot of group think without fraud. And so I want to move the conversation a little bit toward the group think because I think that's a really important piece of this. But before we do, when I hear, I'm not a scientist, when I hear, When I hear about the head of NIH neuroscience, doctoring images, and another leading blood-brain barrier scientist, doctoring images,

and president of Stanford doctoring images, and another scientist working with Cass for doctoring images, a part of me wonders, is there collusion here? Did you find any evidence of collusion in the field, people sharing strategies for how to outwit peer review, how to outwit NIH to draw money in, or is it your hypothesis or finding that image doctoring is just so easy that if you fundamentally believe in this theory

and believe that that theory is most likely to get you the funding, well, look, of course you're going to doctor the image. You don't need to read from anybody else's playbook to do it. Yeah, I think it's the latter. I think it's just too easy. And with the digital tools that are now available, it's getting easier and easier. These problems have existed for a long time. But people don't need advice on how to do it.

They can figure it out. It's just not that hard. And unfortunately, if people have bad motives, then they do it all the time. I mean, I think I can give you an idea of how this kind of progresses, if you want. I've tried to puzzle through this process, this thinking process people are going through because, you know, it seems so important to understand the basis of it. So often I think the way it proceeds is that someone has good motives, and they want to sort of, quote unquote, beautify their image a little bit,

to give it more curb appeal for scientific publishers who want not just truth, but beauty in their pages. And that's not misconduct per se. It's frowned upon, but it goes on and people look the other way. then that same scientist might say, well, I'm getting a weak result here, but I'm very convinced that my science is good science. It's leading us in an important direction. I'm just going to tighten this up, sharpen it up, maybe make a little change here. It's not really fundamentally changing my ideas or the underlying data, but it's going to make this accentuate my result. They find that they get away with it because in many cases, the ability and the interest in the scientific authorities, to closely watch and police these kinds of changes has been weak historically. And so then it's a bit of a slippery slope. It goes from there sometimes, I think, to, I deeply believe in my ideas, but I'm just not getting

the right result. I'm just going to go ahead and change this image to reflect that. I know I'm going to be able to do it in the next experiment. And there you go. You're on the way towards image fraud. And I think this happens over and over in part because people are in a desperately competitive environment where getting the right answer can mean the difference between fame, fortunate success and failure as a scientist who might not even be able to get funding in their field.

We've been talking about folks like Moslige who are giants of the field, but they're representative of just one aspect of the problem you describe in your book. They're not representative of the junior scientists trying to get their first publications who aren't interested in fraud, but need money, feel a pressure to publish, feel this intense interest in finding the next breakthrough. Can you explain to people how the stranglehold of the amyloid hypothesis might have encouraged these less established scientists to bias their own investigations toward this theory? Yeah, you don't have to take it from me.

scientists that I've spoken with and who have been reported on by others have said over and over that they have been advised by senior people in the field to steer away from alternate ideas, or at least to pay homage to the amylide hypothesis and their grant proposals. So what you often see is people who really you can get the hint that they're trying to find out some new information, but they also have to say, we believe we're going to have an effect in our understanding of amyloid proteins in the process of doing this experiment, even if their desire is to explore something else like inflammation or perhaps the viral infection of Alzheimer's disease or other issues, they always have to give a nod to the amyloid hypothesis

and continue to acknowledge that as sort of the direction everyone needs to be moving in. Instead of confronting it and saying, look, let's look in other directions as well. not eliminate all research in the amylaid hypothesis, because there's too much evidence that it has something to do with Alzheimer's, but not everything to do with Alzheimer's. Let me speak up for neuroscientists here who might say, don't throw the science out with a fraud. Yes, this field has been sullied by image manipulation,

and yes, maybe there's too much group-think in neuroscience as there's group-think in every field. But there is genetic and animal study research that does seem to back up the centrality of amyloid cascades to Alzheimer's. And they're going to say maybe we should continue to pursue this theory alongside other theories. I mean, there are still top neuroscientists and biotech startups that are devoting their talent and their treasure to amyloid. The FDA has approved several Alzheimer's drugs that target amyloid proteins.

So I don't believe in steel manning for the sake of steel manning, but I'd like you to do something that might be a little bit tough. I want you to tell me what's the best case that you're wrong and how much stock do you put in the best case that you're wrong? Sure. the best case that I'm wrong is that people will start large-scale testing of anti-amloid drugs in young people. In other words, the idea being, oh, it's not working as well as we hope because we need to go earlier and earlier. And let me just put this into context if those experiments are successful. and they say, okay, removing amyloid proteins from the brain at age 40 or age 50 or age 50 instead of at age 75 or 80, that you're going to see much better results.

You're going to be able to have a preventive therapy. Understand that if these drugs were cheap and without risk, I would be the first person to say, let's go for it, go for it right now, get those large-scale studies underway because we know we can remove the proteins from the brain. There's no question about that. The problem is that they're very expensive and they're potentially very dangerous. Even the possibility of causing death, the ones that are in the market now carry a black box warning from the FDA. And what this means is it's the highest caution risk of death from brain swelling or bleeding.

Now, most people take drugs don't die from them, obviously. Most don't have severe brain swelling and bleeding, bleeding. But there's enough of that going on that it's a cautionary tale. But going younger, that's the best case for why I might be wrong. Charles, there's going to be people who read this book who entirely agree with you, but come away with a very specific conclusion, which is that science is broken, and the NIH is broken, and our academic institutions are broken, and the entire industry is so shot through with fraud and dissembling and doctoring

that we should just shut it all down. We should find some way to reduce funding through NIH, find a way to defund a lot of these academic centers and universities that are doing neuroscience, that they come away from this book thinking, this entire field feels fraudulent to me. what's your message to people who are having inklings of that thought listening to this podcast or might have inklings of that thought reading your essays in the New York Times or the book, doctored?

Yeah, I would say that would be a very, very unfortunate and potentially disastrous conclusion to reach for possibly someday curing Alzheimer's disease and other dread diseases. For these reasons, one is that only a very tiny percent of all. of this research is subject to image doctoring or other types of misconduct, very, very small percentage. The vast, vast majority of Alzheimer's research, notwithstanding the very unfortunate examples of people like Eliza Masliah or Erzlovlovich or some others, notwithstanding those examples, most scientists are honest and deeply determined to cure the disease. Sure, there's been some group think in the field. Sure, there's been some delays. Sure, there's been some very

big disappointments, and people should be angry about that. They should also be angry at scientific institutions that have been complacent in managing these problems, that have been unduly supportive of scientists who need to be examined more closely for their deleterious effects on the research field for skewing thinking improperly. So, yes, be angry. And Yes, demand better. Yes, shake scientific institutions out of their relative complacency and demand that the tax dollars that are spent go towards things that are more important and more impactful. But no, without those institutions that generally serve our society incredibly well that have led to some of the best health care in the world and, I might add, some of the safest drug supply of any country in the world and the most heavily. regulated for good reason to show that these products are good, safe and effective. Please, let's not get in a bandwagon of saying we should defund all those agencies because there

have been some people who've done some bad things. I am not at all in support of that. But I have to tell you that as a journalist, it's tough because I hate to see people misusing the message of my work to suggest that we should tear it all down. That's the opposite of what I would want to convey. And yet, as a journalist, I'm not doing my job unless I call out misconduct and help create the conditions where it can be improved and changed and build up those institutions better. If I don't do that, what I'm in this business for. Charles, for people who love science, this episode will be mostly depressing, but I also want to see your work as being hopeful in a way, because I think you represent a part of the scientific

immune system that has fought back against what is essentially an inflammation of bad science, and inflammation of fraud, doctored images, groupthink. Hopefully your work is part of the cure, and I'm speaking to you now with your book out and its ideas moving into the mainstream. I want to think that the field of Alzheimer's research is healthier today than it was

two, three years ago before your revelations came to light. So in the interest of seeing where this story could go, in the best case scenario, what is the most hopeful interpretation? What are the most promising paths forward on Alzheimer's research?

I feel pretty hopeful about the possibilities of the future for Alzheimer's disease. And that's because even though a lot of new ideas have been crowded out by the amyloid hypothesis dominance, not all have. There are new things happening now,

including, as you already, I'm sure, I heard your story on the GLP1 inhibitor, and Alzheimer's disease, terrific show. That paper recently in nature that was observational that suggested that there was a link between GLP-1 inhibitors and improvement or at least lower rates of Alzheimer's disease. That's pretty interesting stuff,

and right now there's a clinical trial going on that could prove out some of the potential benefits of GLP-1 inhibitors. So I'm very excited about that. that only another year or so before we know the results of that experiment. Second, there's been some very interesting work going on in exploring antiviral therapies. There's some very increasingly accepted ideas that Alzheimer's might have something to do with viral infections that hang out in the brain. For example, herpes virus, which can cause lesions on the body that go away and people think, okay, I'm fine, I'm done with that. but those viruses can sometimes hang out in different organs of the body, including the brain.

And maybe many years later might be related to Alzheimer's dementia. So there's trials going on regarding that. There's the GLP1 trials. These are very hopeful and important next steps for at least exploring new ideas. And I really try to emphasize also that people have some agency in this set of problems that we call Alzheimer's disease. It's not that there's a magic cure. There's no supplement or lifestyle chains or brain game that I've ever heard of or know about that is a cure for Alzheimer's or preventive for Alzheimer's per se. But we know that there are several risk factors that we have a

degree of control over in our lives. High blood pressure, high cholesterol levels, sedentary lifestyles. These are things that we have some agency over in our lives. We can live our best lives and also reduce the possibility of having the worst effects of Alzheimer's. Should we be unlucky to get that disease occur sooner, we can maybe forestall some of those terrible effects. So I would just say people should remember that they are not powerless. Charles Peller, thank you very much. Thank you, Derek.

One thing to remember from today's show is that I fully recognize the political irony of publishing a show about the failures of institutional science during a time when it seems like the Trump administration is looking to cut institutional science, cut NIH spending slash personnel with the National Science Foundation. We live in an era of declining institutional trust. That is clear. Trust in the presidency, in Congress, in the courts, in business are all down among Americans. Trust in scientific institutions is declining to, perhaps as fast or even faster than the rest. Young people and conservatives especially are putting less faith in the NIH or the CDC or the FDA or universities.

They're turning instead to independent media, to individuals rather than institutions. And some of those individuals, I think, are careful and even brilliant explainers and guides, but some of them, I think, are conspiracy theorists who are much more interested in building an audience than in telling the truth. I want our scientific institutions to thrive, but there is a paradox here. Building trust in our institutions requires pointing out when they failed us. The legacy of fraud in Alzheimer's research is absolutely astonishing to confront. And as Charles explains, this isn't about one bad apple, one corrupt scientist.

This is a systemic problem. it exists at the level of groupthink, at the level of pressure to publish, at the level of journals, even at the level of the NIH itself. And people like me who want the NIH to succeed and even grow might feel pressured to brush off a story like this, right? Brush it under the rug, especially with the news that the Trump administration is making plans to cut overall NIH spending. But I think defending these institutions requires seeing them clear. And that means seeing how and when they fail, and explaining how they fail, and trying to fix them. If people like me don't tell stories like this, don't report stories like this, we leave the truth to be told by people who just want to burn the system down. That's why I think this story is so important.

It's absolutely critical to understand how today's systems of science don't work. in order to fix them.