Alzheimer’s Research, Doctored Data, and the Human Cost | Charles Piller – EP 722

30:58So now I'm going to get to exactly your question, the risks that he took. So you're talking about a junior professor at Vanderbilt University, did not have tenure, going up against some of the biggest journals, funders, and authorities, all people and institutions he needed to continue and develop his career to become successful as a scientist himself. And yet he ultimately decided that his journey of discovery was central to helping the public understand this set of contradictions. And that he was trusting me after literally months of discussion about this, that he trusted me to tell his journey of discovery in both Science Magazine and in the pages of my book in such a way that we could try to illuminate the importance of it and to help to try to correct the scientific record in a positive way that could open up new ideas for the field.

32:03So as someone who is not part of the scientific community, which is a very tight-knit club based on what I've seen across universities, would someone in his position first attempt to go to some of the people in the scientific a community themselves and confront them? And then after that confrontation ended in going nowhere, then they come to you or does it not work that way? Well, yes and no. So what Treg did is that he always followed the path of the appropriate way to question research, which is to go to the funding agencies and the journals, the agencies that funded the work and the journals that published it and to present all of his information openly to them and make sure that they had the full set of concerns about a body of work in order to judge whether it's worth looking at and whether his concerns might be well-founded.

33:04And it was only after months and months of being stonewalled by those institutions, months and months of being ignored by the journals that are responsible for the scientific record itself, that he felt that it was appropriate for him to come out publicly through my writing. And so the short answer is yes, he followed the sort of prescribed protocols and found them to be unfortunately not very useful. And this is, I would add, a very typical story. These institutions are sluggish at best in examining problems that occur on their watch, both out of a sense of embarrassment and also out of the problem of trying to guard against people criticizing them.

33:53There's a longer story about it, but the gist of it is, yes, he did approach those institutions and did not get satisfaction. So this isn't a simple thing like you see in the Washington Post or New York Times, Wall Street Journal, where they publish something, someone writes in saying you didn't get all the information right. And you see in the editorial comments that we published this story and it's come to light that part of our reporting was incorrect. So we feel it's important to restate the information. So these publications that we're talking about don't normally do something like we see in a lot of newspaper reporting on a common basis.

34:30No, just to be clear, look, we're all human. We all make mistakes. I have made mistakes in my reporting, although I got to say it's pretty unusual because I'm a careful person and I have great editing and great fact checking. But that said, whenever there's a claim that I've made a mistake, I drop everything and go directly to reinvestigate that issue to satisfy myself that either the questioner is incorrect, or if there was a mistake made that we issue correction. This happens immediately. Not so with scientific journals, usually they spend weeks, months, or even years without doing anything.

35:10Normally, they kick the question back to the home institution of the investigator who's been questioned. So let's take the example of the important experiment from the University of Minnesota from 2006. The journal Nature published this. This is an eminent journal, one of the most important journals of scholarly writing in the world. You might say an equivalent with science, the journal that I work for. And nature basically sat on this literally for more than almost two years before doing anything about it. And actually more than two years, it turned out to be. Now, what they did is they kicked it back to the University of Minnesota.

35:54This is the institution with the most to lose and the least to gain from doing a robust, complete, and publicly accessible examination of concerns about one of its scientists' research. And lo and behold, they went years investigating this. Ultimately, the study was retracted, but we didn't get the details of what the University of Minnesota's investigation was. We didn't get those details because they behaved in an incredibly secretive way. I might add that ultimately, Sylvain Lesney, who was implicated in being most involved with the apparent image doctoring in this study, was retired out of the university, even though he was a young, full professor there.

36:38Very unusual, but clearly a substantial problem that caused him to retire. When you think about the papers and the funding that were all based on the amyloid hypothesis, hypothesis in practical terms, just so the listeners can get some type of sense, like how much time, money, and human opportunity did we lose by chasing a theory that was based on falsified data? Well, let me put it this way. So I want to make it clear that I agree that amyloid proteins and tau proteins have something to do with Alzheimer's disease. I think where I part ways with the progenitors and supporters of the amyloid hypothesis, as the dominant way of looking at the disease is that I don't think they have everything to do with Alzheimer's disease.

37:27And I think that the way in which that idea has been promoted has squeezed out other ways of thinking about Alzheimer's. Because of the scarcity of funding, when so much emphasis goes on one dominant set of ideas, it can be hard for other researchers to get traction in their way of thinking about the disease. I think that is the sort of tragedy of the issue. If I could just expand on that briefly, there has been an enormous amount of fraud and misconduct in the field of Alzheimer's disease, a lot of it associated with the amyloid hypothesis. And that is in part because the dominant way of thinking about the disease presents a big target, and it makes the possibility of incorrect or falsified information more likely to be accepted by the scientific community.

38:17If it fits with the dominant way of thinking about disease, even if it's wrong, even if it's based on fraud or misconduct, it's much more likely to pass muster and to be seen as being correct information. But I want to say briefly that fraud and misconduct is still, in my view, a small part of the overall scientific equation. Most scientists, like most people in all walks of life, are honest and deeply committed to doing the right thing to develop human knowledge and to serve humanity in a beneficial way. And even though I think Alzheimer's disease has been badly damaged by fraud and misconduct, I'd say that most scientists are not in that category.

39:01Of course they're not. If you look at the scientific record, there's been a lot of fraud and misconduct in heart disease, cancer research, diabetes research, basically everything, because a very small percentage of people in every field of life are going to cut corners or even worse. But the difference is that unlike heart disease and cancer and diabetes and other very important human ailments, which have seen enormous progress in the last few decades, which have seen even cures in some cases, we have not seen that in Alzheimer's disease. There's never been a remedy developed that arrests or reverses the cognitive symptoms that are so terrifying and so damaging and really have created the sort of dementia crisis that we have worldwide with Alzheimer's.

39:58And in my view, part of the reason why progress has been slow is that the human brain is an incredibly complex organ and is very difficult to decipher what's going on inside there. So that's one reason. Another reason is that when so much seminal research in the field is based on thinking that has been skewed by doctored images, by falsification of data, and by basically fraud, that undoubtedly that has been a factor in the problem of a lack of progress in Alzheimer's research. So it's multiple problems. Since you brought up things like cancer research, et cetera. One of the things in Doctored that you exposed was a cabal of researchers, funders, and pharma executives who helped enable the deception that went on.

40:54And the reason I'm bringing this up is because it's an entire system. I mean, it's often systems that stop things from making progress or make things like this become something of progress. What incentives did you find that made fraud not only possible, but predictable? Sure. So I refer in the book to something that I call the amyloid mafia. And I want to make it clear that it's not a real organization. It's not a real mafia. These are not criminals, except to the extent that some people who are proponents of issues in Alzheimer's, like some proponents of the amyloid hypothesis and other related scientific factors have engaged in inappropriate actions, have engaged in doctored research.

41:47But what I mean by the amyloid mafia is people whose careers and personal fortunes and paydays from pharma companies and scientific reputations and their legacies as scientists are all integral to this idea of this one dominant way of thinking in the field. And when you have this enormous set of incentives for professionals in the field who are very powerful and who are often the gatekeepers of knowledge, who are prominent scientists, whose work has been cited many thousands of times, whose ideas tend to dictate the trends in drug development and the trends in scientific thinking, when you have them working in lockstep with each other to try to reinforce what is ultimately their professional legacy and to prove out one way of thinking in the field, then you can have the effect of forestalling the ideas that might run contrary to that, or might just complement it in ways if they were not starved for funds, if they were not regarded as a secondary or lesser or not worth pursuing.

43:08And I think what you had in the field is this dominance that crowded out other ways of thinking. Now, I'm happy to say that thinking in the field is beginning to expand. More and more, you're seeing people push back against the singularity of the amyloid hypothesis and to look at the aspects of it that might be extremely valuable to keep exploring, but also to expand out to other ways of thinking of the disease that might in themselves be equally valuable or might in combination with research on amyloid and tau proteins lead to better outcomes for patients. Thank you for going into that, Charles, And I have a follow-up question to that, and it revolves around Big Pharma itself, because many Alzheimer's patients, including my grandfather, had pinned their hopes on the evolution of drugs coming out to help them.

44:01Based on your reporting, how effective or ineffective are these drugs really? Thanks, John. I believe you're referring to two anti-amyloid antibody drugs. Their names that they're sold under are Kasunla and Lakembi. And they've only been on the market a couple of years. And these drugs were developed to strip amyloid proteins out of the brain with the idea that, again, if you do that, you are going to be preventing this cascade of biochemical effects that lead to terrible dementia of Alzheimer's patients. And large trials were done with these drugs. These are human trials where people with mild symptoms of Alzheimer's or what they call pre-Alzheimer's symptoms, very mild dementia or memory loss symptoms, join these trials, take the drugs for an extended period, and then they're compared against a group of people who are given a placebo, which is kind of the classic sugar pill, although in this case, it's not a sugar pill because these are infused through veins.

45:11They're getting a dummy infusion that does not contain any drug in it. And then they compared the results of these two groups. And what they found is to a statistically measurable degree, statistically significant degree, the people who took these drugs, they, just like the placebo group, their cognition declined, but it declined to a very slightly less rapid rate than the people on the placebo. And so you say, well, isn't this a really beneficial effect of the drugs? Yes, they did not reverse the cognitive decline of Alzheimer's. They did not arrest the symptoms. But what they did is they made it possible for people to decline very slightly less rapidly.

45:59Now, so if these drugs were completely safe to take, if they were completely affordable, if they were drugs that did not require potentially harmful infusion process in doctor's offices or in clinics, and they only had a slightly beneficial effect, then why would anyone refuse them who was beginning to experience the symptoms of Alzheimer's disease? But unfortunately, the story told, I think, is not quite correct. So what in the community of neurologists and other doctors who prescribe these drugs, or don't prescribe them in some cases, is that these drugs, the benefits of them as described are so minimal that many doctors, patients, and family members would not be able to notice those benefits.

46:51In other words, the effects would not be discernible. That's how subtle they are. But at the same time, they have potentially dangerous side effects, including brain swelling and bleeding, and including brain atrophy. That's the shrinkage of the brain that occurs more rapidly than the shrinkage that occurs within Alzheimer's disease itself. And so you have these contradictions of potentially dangerous brain swelling and bleeding that does kill people on occasion for the benefits of the drug that are so subtle that in many cases people say it's imperceptible. So I'm not saying that no one should take these drugs.

47:32That's a decision that people should make with their physicians and with their family members. But what I'm saying is that people should not exaggerate the benefits. They should see that these potential benefits are very slight and the dangers are ever present. So all that being said, based on the research that you have done, and I'm going to phrase this in two different camps. For those of us who are younger in our lives and haven't reached the normal point for some of these diseases to take root, what have you found are recommendations people should do? And then if you are in the camp where someone has an early diagnosis for dementia or Alzheimer's, what have you learned through your research that might be appropriate steps for them to take?

48:26When you say an early diagnosis, you mean someone who's beginning to see the very early signs of dementia, who at any age or at a normal, what they call the sporadic Alzheimer's age of maybe in 70s, usually from 65 to 85. Yes. Well, let me say that in my view, Alzheimer's has been subject to some of the same things we see for all kinds of diseases. The two most important being that care and prevention has sometimes been sacrificed at the altar of cure. And so the vast majority of funds for research and development for drug discovery, et cetera, has outweighed the emphasis being placed on prevention and care.

49:15And these are things that can make a big difference in a person's life and experience of the disease and also in trying to forestall the possible terrible effects of Alzheimer's. So let me put it this way, living our best lives through good nutrition, exercise, controlling high blood pressure, controlling cholesterol levels, using your mind, reading, having good social relationships. These are all things that can forestall the worst effects of Alzheimer's if you're unfortunate to be someone who ends up getting the disease. There, in my view, is no brain game or supplement or exercise regimen that will definitively stop a person from getting Alzheimer's.

50:05But we know that this combination of effects, things that pay dividends in our lives generally, can be extremely important in forestalling or preventing the worst effects of the disease. And so I would just say people should remember that they have some agency in their lives. And that's one factor. The science, the scientists who are proponents of the amyloid hypothesis, who again, in my view, have important points to make, but their ideas should not prevent people from exploring other ways of looking at the disease and finding the combination of factors that might lead to Alzheimer's disease.

50:48But I think what they're advocating for is to treat early and earlier with these anti-amyloid drugs that again, as I mentioned, have potentially beneficial effects if very subtle effects on cognition. In other words, to reduce the rate of cognitive decline that people might experience. But when they're describing the idea of giving these drugs to younger and younger people, I think people should be cautious in adopting that advice, particularly people who have no symptoms of cognitive decline, but may have evidence of amyloid and tau proteins in their brain. Young people who have those symptoms, have those evidence of those proteins, might at some point be encouraged to take these drugs.

51:38And I think you need to proceed down that path with great caution because of the potential hazards associated with them. I want to go back to image manipulation for a second. Based on your discoveries, is fraudulent image manipulation rare, or is it shockingly common across some scientific disciplines, such as what you found in neuroscience? John, let me just say that I, again, I just want to emphasize that I think most scientists would never manipulate images, but even a minority of scientists who do can have profound effects on thinking in the field, which is what I discovered in my work. And I would say then that, yes, image manipulation is unfortunately quite common.

52:27And part of the reason for it is that I think scientists sometimes become very convinced of their ideas and ways that they follow a kind of slippery slope where they might make a small change in an image in order to exaggerate the beneficial results of a study and that they see that no one notices that they made an improper change. And they think this is good because I'm very convinced of the truthfulness of my science and the importance of my science. And by making this change, I have created an opportunity to get new funding, funding that I desperately need to prove out the validity of this work.

53:09And then the next study comes along and they see, well, I'm not quite getting exactly the results I want and need to prove my hypothesis, but I know I'm close. I'm just going to make a couple of other changes to reflect well on the experiment. And so you see where I'm going with this. Suddenly you're moving into the direction of outright fraud and misconduct that then goes into the scientific record, skews thinking in the field. And in the case of the amyloid hypothesis, there have been many studies done that are above reproach, but many others that have been done that are based on doctored science, doctored data, that have pushed people in directions that suggest that the importance of this work is greater than it really is.

53:57Given the decades of false starts and misconduct, how hopeful should the public be about the future? Are we closer than we think, or is Alzheimer's still an unresolved mystery similar to pancreatic cancer in the near term? I think in the near term, we're going to be faced with many dilemmas and conundrums in the Alzheimer's field. That said, I do have a lot of hope, in part because I think scientific ideas are opening up a bit. Perhaps I've had some small part in forcing the scientific community to take a good hard look in the mirror and ask themselves, how can we do this better? How can we approach our science with both greater validity and greater open-mindedness?

54:42And I think that is beginning to take hold. Let me give you a couple of examples that I feel very interested in seeing how they come out. And potentially, they could be great developments in the field. One is an emphasis on the infectious hypothesis of Alzheimer's. And this is the idea that latent infections such as that of herpes virus or other ailments could hide out in the brain for years or decades and cause problems such as inflammation that could contribute to or lead to the symptoms of Alzheimer's disease. People are studying these things ever more seriously. There's clinical trials going on right now to see if that idea might be one of great importance.

55:25And I think within the next couple of years, we're going to see some evidence to suggest whether it is or not. So I'm very hopeful about that, adding new information to the field that could be beneficial. The other is GLP-1 inhibitors. These are the new seemingly magical drugs that are used for weight loss and for diabetes and now a raft of other ailments that have taken the world by storm over the last few years. And they're also being tested as a possible preventive or treatment for Alzheimer's disease. And very soon, even perhaps by the end of this year, early next year, we're going to have the initial reading of a big clinical trial associated with GLP-1 inhibitors that will have some, I think, some interesting results to see whether they're heading down a path that could be beneficial.

56:19And so these are the kind of scientific projects that give me a lot of hope and a lot of belief that science is vast. Much of it has not been corrupted. Much of the set of ideas behind the brain and neuroscience and Alzheimer's disease, I think, will bear fruit eventually in ways that can really be hopeful for patients. And in the meantime, we also have the kind of hopeful quality of, again, living our best lives in ways that could help us forestall or prevent some of the serious effects of the disease for years in a way that could really benefit our lives. Charles, you alluded to this a little bit, but I wanted to ask you because it's intriguing to me.

57:10After years of reporting on what you wrote about and doctored, what changed in you? How has exposing fraud at this scale reshaped your belief, not only in science, but truth and the human capacity to self-correct? Terrific question, John. It's been a really difficult journey because I believe deeply in science and the scientific method. I believe that it's one of the greatest, most important developments in human thinking historically. We have reaped enormous benefits from it in medicine and in many other fields, of course. That said, I think the scientific method teaches us that you can't fake information ultimately and get away with it because science is what they call self-correcting.

57:59And what that means is that false information will eventually be discovered, uncovered, and corrected by new experimentation. The problem that I see in science is that because of difficulties in the journals, the funders, the universities, and the regulators of science, all four of those important scientific institutions have deep flaws that have been created the conditions where problems in science, either corruption or just simple error or simple misunderstandings that are part of the scientific research process, are being allowed to remain in the record and to skew thinking in the field for much longer than they need to be.

58:47So I mentioned earlier that, for example, the University of Minnesota was charged with examining the possible corruption of this important study in alzheimer's research and because the university was very slow in doing their work this study remained on the record influencing thinking for many years longer than it needed to be and what i would say and what i have been writing about in my book is the importance for these scientific institutions to up their games to do better at investigating correcting, and enforcing the importance of accuracy and truthfulness in the scientific record. And I say this because I have great faith that these institutions have the ability to do better and reform themselves.

59:40But we as citizens and consumers of science and journalists and everyone, we have standing to insist that they do better. Now, this is different from insisting that we defund them or cause them to be redirected into, in my opinion, sometimes incorrect areas. I don't subscribe to the idea that the way to correct these institutions is to completely, in a way, challenge everything about them and destroy them in a way that, I think to some degree, that effort has been made by people in Washington of late. But what I do believe is that we should not stand for laziness and inconsistent enforcement of rules and an unwillingness to challenge conventional wisdom in ways that is vital to improving the scientific record.

1:00:37Thank you so much for that. I just am curious, what is the next topic that you're now working on to tackle for science? Well, unfortunately, John, I can't talk about that because all of my investigations are under wraps until I'm much farther along in the process. But stay tuned. We're going to have some stuff in the magazine pretty soon that I think will be of interest to your listeners. Okay, great. And Charles, where's the best place for people to learn more about you and your work? The best place is really to go to my website, charlespillar.com. And up there, you can read more about my book, Doctored.

1:01:16And you can also see links to my stories in Science Magazine, the New York Times, and in other locations. And I think if you're interested in any aspect of my work, that's a terrific starting point. Okay. And the last question I'm going to ask you, on PassionStruck, we're all about teaching people how do you create what I call a passion struck life, which you are obviously passion struck about the journalistic reporting that you do. For you, what does it mean to be passion struck? Well, for me, it means you have to be a little obsessive and you have to be deeply concerned about doing something beneficial for the human condition.

1:01:56That's where for me, it's central to my identity. But I have to say that I also feel that for me to explore my passion most effectively is that I have to challenge myself and sometimes not take myself too seriously. And my method of doing that is to spend time with my three-year-old granddaughter who does not put up with any kind of pretension, or she is someone who I love so much and value so much. And spending time with her keeps me honest. Well, Charles, you didn't know this before we did this interview, but I actually have a children's book coming out in February. The title is You Matter, Luma.

1:02:36Once I get some advanced reader copies, I'd love to send one to you. It's a little bit early for her, but she'll be forward before you know it. I can't wait to see it, John. Thank you for mentioning that. Charles, thank you so much for coming on PassionStruck and sharing this important research discovery that you made. It was my pleasure. Thanks for having me, John. That brings us to the close of today's conversation with Charles Miller. This episode stayed with you. That's because it wasn't just about Alzheimer's research. It's about how truth survives or erodes inside powerful systems. Here are three reflections that I'm carrying forward.

1:03:13First, progress without integrity is fragile. When certainty replaces curiosity, systems stop learning. Second, And whistleblowers aren't disruptors, they're guardians. Truth often arrives through the people willing to risk belonging. And third, mattering requires accountability. Human worth erodes when outcomes matter more than honest. Charles' work is a reminder that meaning isn't only something we cultivate internally, something we must defend structurally in science, leadership, and culture. If today's episode resonated, please consider sharing it with someone who cares about medicine, ethics, or the future of truth.

1:03:49or leave a five-star review on Apple Podcasts or Spotify. It's the most powerful way to help these conversations travel. If you'd like to continue the work, visit the ignitedlife.net for episode reflections and practices. Watch the full conversation on YouTube at John R. Miles or passion-struck clips or explore intention-driven apparel at startmattering.com. Next Tuesday, we start a new series, You Matter, with a conversation that shifts from corrupted systems to constrained choice. I'm joined by renowned psychologist Barry Schwartz, author of Choose Wisely, as we explore how the paradox of choice shapes mattering, agency, and regret, and why more options don't always lead to better lives.

1:04:31What we're trying to suggest in the book is that it's important to think of our lives as ongoing narratives, that there's a trajectory to life, that it isn't simply about attaining one pleasurable moment of experience followed by another pleasurable moment of experience with no particular connection between them. That is to say, life needs to have meaning. There are different ways that people can get meaning out of life. And in a pluralistic society like ours, you certainly see that. Until then, remember, truth demands courage. Mattering requires stewardship. And significance grows where integrity holds.

1:05:19I'm John Miles, and you've been PassionStruck.

1:05:32Thank you.