581: Fraud, failure, & new frontiers in Alzheimer's research | Journalist Charles Piller
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What if the very foundation of Alzheimer's research has been built on a shaky premise, one that's held back progress for decades? Today's guest, Charles Piller, is here to unravel a complex story of scientific groupthink, fraud, misconduct, and a hope for a better path forward.

Charles is an award-winning investigative journalist whose work spans public health, biological warfare, infectious disease outbreaks, and more. And his recent book, "Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's," dives deep into a field plagued by controversy and unanswered questions. In today's show, Charles unpacks why the world's long-dominant amyloid hypothesis may have steered Alzheimer's research in the wrong direction.

and how doctored images in the field have perpetuated this costly mistake. Plus, what needs to change to move this science forward? But look, it's not all doom and gloom. Charles highlights promising new areas of research, and he also shares practical insights on lifestyle factors that can help reduce your risk for dementia. You don't want to miss this one. Let's dive into it.

So what is the big lie as it relates to Alzheimer's research? Well, that is indeed the question, Jason. Thank you for asking it. I would say there isn't one maybe single big lie, but there is a confluence of things that has caused Alzheimer's research to have disappointingly slow, disappointingly meager results for patients and for their family members who are caring for them.

Let me put it in two parts. One is that Alzheimer's research has been dominated for decades by a one big idea, and that is something called the amyloid hypothesis. And very briefly for listeners, this hypothesis is based on the idea that something called amyloid proteins, and these are what people may remember as the sticky plaques that emulate the brain,

and other forms of amyloid protein that are a little bit different, over time, cause a cascade of biochemical effects that lead to Alzheimer's dementia.

That idea, that central idea, has been in force for a very long time and has been dominating scientists' minds and research and funding and drug development, but unfortunately has yielded very meager, if any, really substantial results for patients. So that's one part of it. The other part of the big lie, if you want to call it that, is the very unfortunate set of circumstances that

In Alzheimer's research, we have seen an enormous amount of apparent image doctoring in seminal papers and many other papers that have influenced thinking in the field. And when I say image doctoring, what I mean is that scientific images that purport to support the premises of experiments that

Steer thinking in the field have been improperly altered or apparently improperly altered to support a false premise. And these two factors, the combination of

the dominance of a single hypothesis and apparently wrong thinking in the field influenced by important work that may have been based on false pretenses. These combination of things has resulted in, I think, unfortunately, a lot of disappointment in the field of Alzheimer's. There are other factors, of course, but those are pretty clearly part of the puzzle.

A lot to unpack there. So the subtitle of the book is Fraud, Arrogance, and Tragedy, because it is a tragedy in the quest to cure Alzheimer's. And as you so notably pointed out, we haven't made much progress here at all. We've made tremendous progress in other disease areas. And so in terms of this false hypothesis, the amyloid hypothesis, where we subsequently spent

our lion's share of time and resources chasing this false premise. How do we get to the amyloid? Was there fraud in the amyloid hypothesis or was it just

Not thorough. Like, let's start there and then move on. Because when you're talking about doctor images, that's flat out fraud. It can be. Yes, absolutely. So let me take us back all the way back to the beginning, just briefly, to give people the context of why the amyloid hypothesis developed. So in 1906, Alwa Alzheimer, the guy who the disease was named after, died.

made a famous study of a patient who was suffering from dementia. He was a pathologist and a clinician, and he eventually, after she died, he did an autopsy, and he found in her brain a couple different kinds of proteins. One was the so-called amyloid proteins, and the other was something that we call tau, which is the

so-called tangles within neurons in the brain. So these two proteins, plus dementia, became the definition of what we call Alzheimer's disease. And because of simple demographic realities, nothing that significant was done to study the disease for many decades. And what I mean by that is that until the 50s, 60s, 70s,

We didn't have the medical tools to really radically extend lifespans for most people. And with the advent of antibiotics and vaccines and other medical techniques and really excellent progress on killers like cancer and heart disease and diabetes,

human beings have managed to really extend our lifespans in many ways. And because Alzheimer's is a disease of the elderly primarily, it means that many, many more people were having Alzheimer's late in life, and it became a very important disease that deserved an enormous amount of attention. So back in the 70s and 80s, the government began to really dedicate itself to more research. So

Because of the definition of Alzheimer's, amyloid plaques and these tangles in the brain cells, and dementia, amyloids became an obvious, obvious way to look at the disease. And what happened was this hypothesis of this cascade of biochemical effects became very popular for logical reasons. When autopsies are done on sufferers of Alzheimer's,

Alzheimer's after death, they often, they always find some degree of amyloid accumulation in the brain. There were contradictions, of course. It's a complicated disease. And

You know, one of the contradictions was that they also find amyloid proteins in the brains of people who had no cognitive decline after they died. So it's confusing. It can be confusing. But there was enough evidence of amyloids involvement, and everyone thinks that there is some involvement of amyloids, some association with Alzheimer's.

that it became a logical thing to look at. So it sounds like more a case of correlation, but not necessarily causation. And that's where we went tremendously wrong. Many scientists think that that might be the case. There's a lot of

new thinking about Alzheimer's that have been questioning whether this singular focus on amyloid hypothesis has well served the community of scholars involved in this. And of course, you have to ask the question, when so much emphasis is placed on one way of looking at the disease, a complex disease that people are still unfolding the mysteries of,

The question is what is lost in the case of Alzheimer's disease when the majority of funding I'm talking billions of dollars the majority of mindshare in the scientific community and the majority of credibility among the institutional authorities of science the journals the funders the drug developers the regulators

universities. Everyone was on the bandwagon to a significant degree. And I think it would be fair to say a kind of, as you phrased it, a kind of groupthink may have seized the research community to a degree that perhaps is somewhat unhealthy and has crowded out other ways of thinking that themselves we don't

We don't know if they'll eventually be fruitful and prove to be instrumental to securing the disease because they haven't had this degree of attention that perhaps they need to have in order to be learned about fully. Yeah, it's, you know, when I first heard about this story and read your excellent book, Doctored, which I encourage everyone to pick up.

I just couldn't help but think how broad the implications are. And it is very scary.

when we think that trust in the quote-unquote medical establishment isn't exactly at a all-time high, and we hear about this, and you mentioned groupthink. But before we go to the broader implications, I want to go back. So okay, everyone's operating under this potentially wrong premise, but we've got brilliant minds, and we've got a lot of funding. And yet, in this process, over decades, there aren't many people raising their hands and saying, maybe

Maybe we got this wrong. They're completely buying in. You mentioned people are fabricating findings, doctoring images. Talk through a few examples. And I want to get into motive.

Sure. So let me give you an example that I think is very central to this idea. And then I'm happy to talk about what I think is going on in the minds of scientists who are cheating. And with the caveat, of course, that I'm not a mind reader, I can only surmise.

But this is an example that actually was at the genesis of my interest in writing a book about this topic. Just to take you back a few years, back in 2006, this was the 100-year anniversary of the discovery of Alzheimer's disease. So kind of an interesting juncture in the history of the disease. And

a very important paper was published. Now, the context is that at that time, the amyloid hypothesis had already been pursued for a very long time since really the early 90s. It became pretty dominant in the thinking of the field. And a bunch of different remedies had been developed, antibody remedies. So the body, as most listeners know, produces antibodies that fight off illnesses, viruses, bacteria, etc., infections.

And these remedies that were produced were these artificial antibodies produced in a lab that would then be put into a person's body and they would fight the amyloid plaques and try to remove them from the brain. And even a vaccine was developed that had a similar goal. And what was learned from these antibodies

experiments with people is that the substances that were developed, the drugs that were developed, were extremely good at removing amyloids, but not good at all in arresting the symptoms of Alzheimer's or improving people's cognition. So what we had was a failure of results for

meaningful results for patients, but a success at the target, the drug target, removing the amyloid plaques from the brain. This was very discouraging to people in the field, to drug developers and scientists and patients and doctors, of course. Very discouraging and

Because this was the big idea and they hoped it would work. Everyone hoped it would work. And so there had been some discouragement and questioning and skepticism rising about this way of operating. And then in 2006, a seminal experiment was done by researchers at the University of Minnesota. And this experiment...

with collaborators, I might add, from other institutions. And this experiment was very clever. And what it did was it took genetically engineered mice that were programmed to produce copious amounts of amyloid proteins in the mice's brains. And the proteins were extracted from the mice brains and then purified a certain kind of protein

certain kind of amyloid protein was purified out of the sample. And this is something they dubbed amyloid beta star 56, kind of a catchy name, star protein. And this protein was then injected into rats. And the rats were said to develop symptoms of memory loss that they compared to the memory loss that people experience in Alzheimer's disease. So what you had was for the first time,

kind of cause and effect experiment that suggested that a particular substance, in this case the star protein amylase beta-star 56, could cause dementia. And so the field pounced on this. It became one of the most cited, revered studies in Alzheimer's science for many years.

And people started to say, okay, this revives our confidence that we're on the right path. This really made the field

realize that maybe we haven't gotten the right drug yet. Maybe we haven't gotten the precisely right target of the certain kind of amyloid protein in the brain that we need to be removing in order to improve the experience of patients. But we're on that path, and we're going to do drug development that heads in that direction. And enormous sums of money were poured into the field to target these special kinds of proteins that

They're called oligomers. It's kind of a wonky term, but it means a kind of amyloid protein that is soluble in the spinal fluid that bathes the brain, not sticky plaques that is sort of the classic understanding of what amyloids look like in the brain. And so a lot of drug development was done, etc. And unfortunately, you still continue to have failure after failure, experiment after experiment.

These drugs became excellent at removing amyloid proteins from the brain, but not good at making people's experience better. All right, so that's the background. In 2022, a scientist by the name of Matthew Schrag at Vanderbilt University, working in his spare time on integrity issues in science, which is a subject that he became an expert in, he and I had been talking about another case, but we

He sort of stumbled on this experiment, this 2006 experiment that was published in the very important scholarly journal Nature, one of the most important in the world. One of the most prestigious in the world. Absolutely. That's part of why it got so much attention. It was the imprimatur of arrival in the important scientific community. People really pay attention to you when you get in that magazine. So Schrag said,

had been examining a bunch of different images from different scientists, and he ran across this scientist from the University of Minnesota, Sylvain Lesnay, who was the first author of this important 2006 study in nature. And Schrag was evaluating some images in that study as part of an

exercise, he was essentially trying to develop new techniques for understanding the validity of scientific images associated with a different project he was working on. And when I say the validity, what I mean is that it had been known by that time by many people that using programs like Photoshop, you can move around parts of an image or

change the look or intensity of certain parts of an image to display ideas that weren't well supported by the experiment itself. And so what we call image doctoring. And so Shrag was looking at this carefully. And if it's okay, Jason, maybe I'll just take one little tiny step back and explain what kind of images, visually what they look like for readers. So for listeners to understand what we're dealing with here.

principally it's two kinds of images. It's something called micrographs, which in this field mean highly magnified images of tissue, brain tissue from mice or humans, depending on the circumstance. And, you know, doing things to the images that

illustrate techniques or ideas or effects of drugs within these micrographs that are different from what was really found in the experiment. So the other is something called Western blots. And this is a very common experiment in science, not just in Alzheimer's disease, but in a wide range of biomedical sciences. And what

What it does is it takes samples of tissue or blood and it divides out the different kinds of proteins that are in that sample by molecular weight. So that's a particular way of characterizing different elements of the protein and how much of the protein is present in

and what kinds are present. Very important in tests that are involving what's happening to the proteins in the brain. You need to do these Western blots to have an understanding of that. They look like a series of stacked bands, kind of irregularly shaped stacked bands. And when scientists improperly manipulate these bands, they can suggest outcomes in an experiment

results in an experiment that might not have actually occurred. So these are the images we're talking about. So what Schrag was doing is he was examining micrographs. He was examining Western blots and trying to ask the question, do these look right? Do they seem to be completely consistent with what the experimental hypothesis was saying and the results as described? And you can put them through the paces of examining them with other software programs to try to see, hmm,

This one maybe doesn't look quite right. And what he found was that there were a number of images within this seminal 2006 paper that

that looked just wrong. They looked like they had been digitally manipulated to produce a result that was not actually found in the experiment. So let me just say, this was a moment where Shrag and I were on the phone talking about this. This was in January of 2022. And we were both kind of stunned and asking ourselves, what are the implications of this? This very important, pivotal experiment that had

not been the only experiment that was influential, not the only experiment that pushed the field in the direction of exploring these so-called oligomer forms of proteins in the brain that might be related to Alzheimer's, but it was a very important one that influenced the spending of enormous sums of money over many years. And he and I both realized at that time that we had something that was very important to help validate and

try to understand better. He did an enormous additional amount of work on that paper and other papers that came out of the same lab, the Lesney Lab at the University of Minnesota, and also colleagues of theirs, including an incredibly important and influential scientist by the name of Karen Ash at the University of Minnesota, who I might add, did not... My further reporting showed that I didn't find any evidence that she personally

was involved in any image manipulation, but her name was on the paper. It became a very famous and important paper, and she greatly benefited from it in her career. So it was an awkward situation to say the least. So this example, when I published an article about this in Science Magazine, another important scholarly journal that employs me as an investigative journalist, it hit the field like a ton of bricks and a

Rightfully so.

This is an opportunity for the field to take a good hard look in the mirror and ask the question, have we been too tightly focused on one way of thinking here? Should we broaden our horizons? The other side was saying, oh, we always thought this experiment had problems and we never took it seriously and the field is fine. We're just going to proceed as we've always done. And ironically, most of the people who were taking that position publicly were people who had cited this study by Lesney et al.,

in nature dozens of times in their own scientific work as the

important subtext and basis and justification for some of the ideas that they were promoting in their own studies and their own work. So it was really quite a pivotal moment for the field. My dad works in B2B marketing. He came by my school for career day and said he was a big ROAS man. Then he told everyone how much he loved calculating his return on ad spend.

My friend's still laughing me to this day. Not everyone gets B2B, but with LinkedIn, you'll be able to reach people who do. Get $100 credit on your next ad campaign. Go to LinkedIn.com slash results to claim your credit. That's LinkedIn.com slash results. Terms and conditions apply. LinkedIn, the place to be, to be. I'm sorry, this has been a bit of a digression, but... I love it and I commend you. Like this was, this is a huge moment for civilization.

Alzheimer's effects, I forget the latest numbers offhand, but millions of people in the US, it's growing and we've wasted decades. So with that said, I want to get into, before we move on to implications and what do we know for sure, I'm thinking a lot of what went wrong? What can we learn from this? So I think of a couple of buckets. I think of the system. So the system being, I'm working at a university,

I need funding. I got to go get my lab funded. I got to get my research funding. And maybe that system and how that doesn't necessarily reward independent thinking and maybe rewards a herd mentality where someone maybe makes a potential breakthrough and

funds all go towards backing this and so if you want to gain funding and do research you maybe have to go in this direction so maybe that's it maybe it's i'm thinking it's like a cousin of group think system doesn't necessarily reward independent thinking for someone to go against the consensus it's a lot easier to just stay with the consensus and maybe where the resources are financially for your lab then be a dissenter right

I think about desire for recognition. So you're not a mind reader, but what's your take on the variety of factors at play that led us astray for decades? Aside from the fraud, which is a whole other egregious, like maybe we'll touch on it for a moment, but put that aside for now. I think that's a very important question, Jason. There are some perverse incentives in academic practice.

work in medicine, academic medicine, and in science, the scientific enterprise generally. As you already stated, there is the pressure, publisher-perish pressure, for young scientists is extreme for all scientists, but particularly young scientists getting started in their career. And

I think to a degree, particularly in Alzheimer's, but in other fields as well, there's a pressure to migrate towards the conventional wisdom. And thinking radically, thinking differently can sometimes be discouraged because, as you say, it's difficult to get money for it. You've got to keep the lights on in your lab if you're going to be a successful scientist. So that's one thing. The other is that there's a tendency to push volume over quality research.

in scientific papers. So people get promoted when they publish a lot and sometimes not enough emphasis is made on the thoughtfulness and clarity and contributions of a smaller number of publications.

You know, I should say very clearly that there have been institutional failures and it's resulted in a large number of Alzheimer's studies that I describe in detail and doctored.

that have been based on apparently false images, false scientific data, and in my view, have had a big influence on the field. And of course, there's many examples of that in the book, and we can talk more about it. But I want to address this question of what went wrong that you asked, which I think is a critical one. So first of all, let me say that I think the institutional failures have included the funders like the National Institutes of Health,

The regulators like FDA, the organization that tries to ensure the quality and safety of our drug supply,

universities whose professors have sometimes transgressed, and journals that are the gatekeepers of scientific knowledge. All of these institutions have been historically extremely lax, extremely basically asleep at the switch regarding checking papers for possible misconduct. It's really tragic because

In my view, these are institutions that we should all be very grateful for because our country is lucky to have really important levels of quality control. Some of the greatest science that's been ever done has been partly due to the system we have in place that in many ways has performed incredibly well. And as a result of that,

It is befuddling and puzzling and really just tragic that these organizations have not put much emphasis, until quite recently, on understanding the role that possible misconduct might be playing in steering scientific thinking. And when I say steering, what I mean is that it's

it's not that this sort of misconduct is rampant everywhere in science. I don't subscribe to that at all. I think the vast, vast majority of scientists are deeply determined people of integrity who joined that kind of life because they feel enormously concerned about bettering the human condition. It would be a mistake to kind of lump everyone together and say it's just a

a morass in a way. So I don't want to put that out at all. Yeah. And just to double click on that for a moment. Look, I do believe scientists go into this field because they're passionate about science. They want to do good work. They want to help people. So I do think everyone starts from a good place. However, I think my view without knowing these people personally, my guess is something happens in the process.

maybe i got to do something to keep the lights on i have to make a hard choice you know maybe maybe i miss something maybe i'm working 20 hour 20 hours a day maybe i'm short on sleep maybe like there are a variety of factors but but i want to get like i do think my view is when you when you when i'm hearing you say quantity i'm hearing the system

My guess is there are a variety of factors that maybe led to this versus, you know, the quote unquote evil mad scientist who's, you know, a narcissist and will do whatever it is to become famous.

There are those. There are those. But there are very few. There are those, but very, very, very few. I agree completely. So let me just lay out two things. So I can tell you what I think is going on based on surmising the experience that I've seen over and over again, the cases that I've looked at, dozens and dozens of cases.

But before I do, I want to put it just a little bit in the context of Alzheimer's disease. So I think that there is a small amount of misconduct in every field, every human endeavor. Scientists are no different. They're people. And of course, there's corruption in science. Of course, there are episodes of misconduct. That said, Alzheimer's is a particularly tragic situation because unlike many of the other major killers like

heart disease, cancer, there are a lot of remedies that have been developed for those diseases that have been very effective. There is hope for all diseases, including Alzheimer's, and we can talk about that too. But what we have now are treatments and techniques and even things like healthful lifestyles that can greatly influence the outcome of a cancer or heart disease patient's life. And so it's kind of incredibly tragic that with Alzheimer's, if

the influence of misconduct has steered things in a wrong direction. It's just that much more heartbreaking for patients and their families. Now, here's what I think may be going on in a lot of these cases. So there is something that is called beautification of images in the scientific community. It's kind of a term of art. And it means that scientists are taking images that

They're fine, but maybe they could be just sharpened up a tiny bit, not changed in a material way that really changes the outcome of an experiment, but made to look better to add a little what you might call curb appeal for journal editors. So we'll call it like a filter on Instagram. I'm making the photo a little bit better on Instagram. Something like that. Right. Or just removing a little tiny corner of it that...

you know, just looks ugly and they want an image to look perfect so that a journal editor will say, ah, I want that paper in my journal. And that is not appropriate behavior in science, but people look the other way because they don't think it has a material effect on the outcome of an experiment. So there's that. And then a person might then get kind of mediocre results that have some

They, to some degree, show that their hypothesis for the experiment made sense, but they're not very strong. And they think to themselves, I know I've got the right result. I'm just going to sharpen it up a little bit in this image so that it's more visible to the reader.

I'm not changing the outcome of the experiment. I'm just making accentuating it a little bit. And they do that and it looks good and they get the paper published and they realize no one really looked too carefully at that and everything went fine. And they thought, okay, that supports my idea. All the peer reviewers and the journals thought this was great. So I'm sure that I was on the right track and I believe deeply in my science.

And then you end up on a potentially slippery slope where someone who might believe deeply in their science, or perhaps even it's just a cynic and someone who is engaging knowingly in misconduct, might take an image and really change it and say, okay, I didn't get exactly the result I was looking for, but I still feel like I'm doing things that are good and important. I'm just going to make it look right so that this experience

experiment might have influence. I can continue my work in this lab because I'm going to get more funding. I can impress my colleagues. I can impress institutional authorities with my acumen as a scientist. And what's the harm? Because I feel so convinced that I'm right and I'm going to be able to prove it down the line. And you know what? I do agree. It's very helpful. And I do agree with your statement that you believe it's a very small percentage of fraud or just poor findings, however we want to classify it.

But I'll quote Dr. Schrag from Vanderbilt, who you mentioned in the book, and he says, quote, it doesn't take that higher percentage of fraud in this discipline to cause major problems, especially if it is strategically placed. That one was a zinger for me because...

I do think most people are good. Let's just say it's, you know, one-tenth of one percent. If strategically placed, very difficult to find. Okay, and can cause major problems. It can, and because the institutions of science have not been aggressive in managing this problem...

Scientists who have engaged in misconduct have, in many cases, found that there are no really big penalties for them. Consequently, I think some have decided to roll, dishonest people roll the dice. They think, okay, I'm probably not going to be caught. And even if I'm caught, the consequences might not be very significant for me until recently. And so, you know, I know most about this, about the field of Alzheimer's research and neuroscience and

So I've written a lot of articles about it, and there are consequences for scientists who have been implicated in these things. But you'd be surprised. Sometimes the consequences are far less than one might imagine because these institutions are too lax in their approach to it. Now, Jason, if you'll permit me, I just want to make something very, very clear. There are many attacks on science going on in our society right now, and science writ large. And

on the institutions of science, institutions like the NIH and FDA and universities. And personally, I find these attacks very, very challenging

And I abhor some of the comments that are being made. I do not subscribe to the idea that we need to tear everything down and rebuild and that people should be just unloaded from these agencies because they have done a bad job or something like that. I think these institutions mostly do a great job in most of what they do. It's just that they've been basically complacent.

on this issue and they must take the initiative to reform their activities in this way, or it will be done for them by people who hate the agencies or, or are too highly critical. And I got to tell you, that is going to be ugly if it happens. Well, I think of two things. I think of the quote unquote system and the system is not perfect. And I think we need to change the system. And I, then I think about groupthink.

And I think groupthink with science is,

is dangerous and that most great, the leaps and bounds we've made in science over, you know, beyond decades have always been, have come from places that, you know, from people who were maybe frowned upon, from people who were outsiders, people who thought were crazy, you know, the list goes, you know, we can start with Edison. There's a long list. And how do we get back to a place where,

where we can minimize groupthink. And I don't think we tear down systems, but create systems that have more checks and balances. And that's difficult. There's a lot culturally. There's a lot institutionally. These things don't happen overnight. So with all that said...

I want to get back to Alzheimer's and where we are today. What do we know for sure? If I'm listening and Alzheimer's runs in my family or it's of concern, and I'm thinking like, oh great, this is something I'm concerned. I think about all these other diseases. There's protocols. There's pharmaceutical interventions. There's lifestyle interventions. And there are people who have had some success with lifestyle intervention with Alzheimer's, but there's no great protocol.

pharmaceutical. There's no great intervention in the way that there is with heart disease. What do we know for sure? Are we at square one? We're back to the drawing board. Well, we know a lot, but there's an enormous amount of uncertainty in the field. And obviously, I think that the field should broaden its horizons, think more widely about what

possible biochemical things might be going on and also how you might attack those. So let me answer the question in a slightly different way. This book that I've written has a lot of discouraging things described in it, but it's not just discouragement. Reported the history of what happened in this field for decades. So...

You know, it has that very strong element running through it. But I would like to emphasize that there are a lot of reasons for hope in the field as well. There's some interesting ideas that are bubbling up that I think within a few years, we're going to know a lot more about, possibly within even a couple of years. And so just to backtrack slightly to address your question directly. So you're absolutely right. There's no magic bullet for Alzheimer's disease, whether you already have it

or if you are afraid of getting it, or you might have a genetic predisposition in your family that make it more likely that you might eventually get Alzheimer's disease. But I want to mention three kinds of experiments that are going on right now that are different from the amyloid hypothesis approach to Alzheimer's disease that could bear fruit. One is the

the so-called infection hypothesis that latent infections from things like herpes virus might be hanging out in the brain many years after the person who had things like cold sores from herpes have subsided and long forgotten might be an influence on Alzheimer's disease. And there's actually clinical trials. These are experiments with people for safety and efficacy studies

of drugs that could attack that in the brain and maybe have an influence on Alzheimer's dementia. That's one.

Another one that is fascinating to me is the use of these GLP-1 inhibitors. This is the sort of magical weight loss drugs for obesity and diabetes, et cetera, that have been sweeping through society in the last few years that are also being tested as a possible remedy for Alzheimer's dementia, early stage Alzheimer's dementia. And

I think within, probably by the end of 2026, we're going to have some results from a big trial that's going on that would give us some answers about whether that might be a useful intervention.

There's really fascinating studies going on about the so-called tau proteins. These are the companion to amyloid plaques that are actually inside the nerve cells of the brain. And, you know, that work needs some years to develop, but it's somewhat hopeful that it could be a tack on the problem that we'll see some benefits down the line.

But I want to say quite clearly that you're completely right, that there aren't any interventions that can prevent Alzheimer's per se. There aren't any interventions that can cure Alzheimer's. There's no drug that can arrest, let alone reverse, the symptoms of Alzheimer's. But we have agency as human beings. We do.

know for sure that there are certain risk factors in contracting Alzheimer's disease. One of them is high blood pressure. One of them is high cholesterol. One of them is living a lifestyle where you're not exercising or eating a healthful diet. These are all things that to some degree we can all control in our lives. And while they are not a cure and they are not

sure-fire prevention. We know that people who pay attention to these things in their lives can reduce the risk for the worst forms of Alzheimer's disease or at least

delay the onset of Alzheimer's. And that's worth thinking about, not just for Alzheimer's, but just for our general health and well-being and happiness in our lives. 100%, as we say here a lot, your genes are not your destiny, and lifestyle can get you very, very far. And what's interesting, as an aside, you mentioned Ozempic, the GLP-1s. There are many longevity doctors I know who are using very low doses of GLP-1s,

for people who do not struggle with obesity or diabetes, but they're using it for longevity benefits, specifically the brain benefits, as you mentioned. I think that's interesting. You're an investigative journalist. I'm sure your brain's thinking about lots of other areas. Does anything else post this book? I'm sure finishing a book, next thing you want to do is write another book. But

Are there other areas in science where you said, hey, maybe there's something going on here as well? Well, as you might imagine, I receive just an enormous number of emails from scientists and from patients and others out there. They're all trying to be your friend now. Well, people want me to look at things that they think are important and important.

I have to say that, you know, it can feel a little overwhelming because I get so many of these suggestions and many of them are really fascinating.

I can say I can't reveal precisely what I'm going after next, but I can say that I'm working on another Alzheimer's story that I think is interesting and provocative, and I hope to have that out before too long. And other kinds of science and medicine really need close attention. I'm sure I'll be jumping into some of those in the future as well. So if you could wave your magic wand...

unlimited resources to make this happen? How would you prioritize fixing this? What I would do is I would

try to create the conditions where journals, funders, and regulators take this more seriously and to reform their practices so that they are more aggressively examining and correcting the possibility of misconduct in their realms. And honestly, I hate to say it, but they don't really have that much choice in my view.

If they don't get going on this and take it more seriously, they're going to be forced to in ways that I think will be very disruptive of their operations by people who don't have necessarily

necessarily the most thoughtful best interests of improving science and medicine in mind. And so I'm asking and I'm expecting that these institutions will try to do better in the future. Well, we hope so. Charles, thank you so much. Everyone go pick up Doctorate. I'm sure you'll win lots of awards beyond many bestseller lists. Incredible investigative reporting, great storytelling. Just congratulations. Thank you. Thank you, Jason. I really appreciate your time and interest.