[music] I'm Alexander Heffner, your host on The Open Mind.

I'm delighted to welcome our guest today, investigative journalist and author Charles Piller.

He's author of the book Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.

Charles, a pleasure to be with you today, thanks for your time.

Thank you so much for having me, Alexander.

Charles, when did you, in your research, first discover that something was awry in the, search for Alzheimer's cure?

In the process that was, being undertaken by, researchers and, people who were purporting to cure Alzheimer's.

So this traces back to 2021, and I was tipped to a source who had apparently very credible information about the existence of many studies associated with a drug called simufilam, an Alzheimer's drug created by a company called Cassava Sciences.

And that's a long, kind of sordid tale about a company that developed a drug based on apparently fraudulent science associated with doctored images in basic science behind the drug's development.

Now, if I could just pause on that one for a minute and move ahead a little bit, the source that I was referring to is a guy by the name of Matthew Schrag, who's a neuroscientist at Vanderbilt University and in his own time, aside from his work as a professor there, he started to become an expert in forensic image analysis.

And he started to try to look at whether these studies from Cassava Sciences were studies that were credible in regard to the basis for developing this drug, simufilam, for a population of Alzheimer's sufferers.

And in the course of doing this, he also started to look more broadly at Alzheimer's research, asking himself this question, if some studies were based on doctored images, was this a problem that the field more generally had?

Is it a problem that required a deeper look?

And, that's where really it all began for me.

And really with a very profound finding about an important Alzheimer's study.

Now, of course, your book is the authoritative account of this.

But for those watching now, what was the answer to that question, about how widespread this abuse was?

Corruption in research?

In the endeavoring to cure Alzheimer's.

How pervasive was the problem?

The problem is very pervasive in the sense that some very important figures in the field, I have found in the course of my reporting for the book, reporting that was greatly supported and validated by a team of forensic image sleuths, they sometimes call themselves, who are able to distinguish the presence of image manipulation and important research.

Now, when I say the problem is important and goes pretty far in the field, I don't want people to get an exaggerated sense of what that means.

It's important, and it has skewed scientific thinking and in my view, has slowed the search for a cure for Alzheimer's.

But it would be a very bad mistake to say, because some research has been doctored, some research has been the result of either misconduct or even a kind of outright fraud that all research is suspect.

This would be a very misguided way to review it, and particularly in these political times we're living in where some have used, important findings of, you know, bad things happening in science to tar all of the scientific enterprise.

That's something I would never subscribe to and would want to resist.

Understood.

If you were to broaden your discussion of the field.

Would you say that the most effective Alzheimer's drug on the market today, is above reproach, has undergone scrutiny, but is not in the category of suspect?

Well, right now there are a couple of drugs that are available to Alzheimer's patients for the treatment of dementia.

So there's a lot of drugs on the market for other symptoms of the disease, like sleeplessness or anxiety, that have been used for a long time with some degree of success.

But the really, the holy grail that scientists are looking for are drugs that arrest or reverse the symptoms of dementia, that are the fundamental problem with Alzheimer's, and the reason why people feel so afraid and desperate about this disease, because it slowly takes our memories and then our ability to function in everyday life.

And finally, even a kind of sense of self we have associated with who we are as people.

And so any drug that could intervene and either halt those symptoms of decline or reverse them would be an incredible boon to humanity.

Now, the drugs that are currently available are drugs that have what they call statistically significant benefits of slowing cognitive decline.

So patients who take these drugs, they're still getting worse.

They're still continuing to have a worsening symptom of dementia as a characteristic of the disease.

But compared to people who are not in the drug, according to these studies that have been done, these patients, their decline is a little bit more slow than those who are not taking the drug.

Now, let me just put that into perspective.

It is so subtle a difference that many clinicians, patients and family members would not perceive a difference.

In other words very, very subtle.

Hardly a breakthrough drug.

Now, that said, I don't have any evidence that these specific drugs were based on fraudulent research.

They're legitimate drugs developed in a legitimate way.

However, their efficacy is small and their potential hazards are great at times.

And what Schrag and you exposed in the manipulated doctored images.

Was that a drug that was perceived to not slow but reverse memory loss?

So was it in this category of drug that you're kind of alluding to that really hasn't been achieved yet.

Yeah, and this particular drug that kicked it all off is, called simufilam from Cassava Sciences, and the claims were that it could actually improve cognition.

So, reverse the symptoms of Alzheimer's disease.

And, those claims proved to be false, and eventually the drug crashed and burned.

It was an example, I think, of not very good regulatory oversight by the Food and Drug Administration that it was able to pass through so many hurdles and make many millions of dollars for, people who were behind the drug.

However, the drug itself was based in part on studies that were apparently fraudulent and on statements that were apparently untrue about its efficacy.

So this is a terrible, terrible story, but I would say that that drug is not that representative of what's going on in the field.

The field's been dominated, for decades by a particular way of looking at Alzheimer's disease called the amyloid hypothesis.

And just to go back very briefly, if I may, to provide a little bit of context.

So let's go back to the genesis of Alzheimer's disease, discovered in the early 1900s by, of course, the namesake, Doctor Alzheimer in Germany.

And what he discovered in his work.

He was a clinician and a pathologist who's a doctor who does autopsies and examines tissues for signs of disease.

And he had a patient who was suffering from terrible dementia.

And when he autopsied her and looked inside her brain, he saw, what would come to be known as the characteristic signs of Alzheimer's disease.

These so-called plaques, sticky plaques that are a type of protein called amyloid protein in the brain.

And second, another protein called tangles for their tangled shape.

That is a kind of protein called tau.

And so this combination of plaques, tangles and tau became the defining characteristics of this disease.

And, fast forward many decades, the disease, you know, didn't get a lot of attention really for decades because of a simple demographic reason, which is that there weren't enough old people living into their 70s and 80s, which is the characteristic time for people to, end up having Alzheimer's disease, for it to be a big scientific issue in our society.

And so what happened is, of course, a number of incredible breakthroughs in cancer, and in heart disease, stroke, diabetes began to extend human lifespans.

And suddenly we had a population of very old people in our country by the 70s and 80s.

And it's kind of a good news, bad news story.

The good news, of course, is it's great that people are living longer lives, more healthful lives.

But it's terrible, of course, that now there was a higher prevalence of Alzheimer's disease.

And that's when a lot more attention was placed on these ideas.

On the ideas of how do we go after this terrible disease and the idea, this hypothesis about amyloid proteins really became the primary one for how, people viewed the disease for decades, but unfortunately not yielding very much in the way of very strong beneficial results for patients.

I want to go back to the, bad science, or faulty intelligence, that you shine a light on.

I know you say you don't want to at all besmirch the industry as a whole.

Or say that it's the majority of medical research.

But, I am drawn to, stories about, Vivek Ramaswamy's involvement in an Alzheimer's cure project, which seemed to be motivated by the same thing, to try to monetize, a process for an end product of shareholder wealth as opposed to, the assignment at hand.

I don't know if you follow, the drug, and the story that Ramaswamy was involved in and his family, I think, too.

But are there parallels with what you exposed?

And even if it's not the majority of practice, is the starting point for anyone who sets out to cure Alzheimer's, not in fact, curing Alzheimer's, but shareholder profit?

Well, that's an excellent question, Alexander.

And one that I've thought about long and hard, of course, in the course of reporting this book.

So our system of drug development is a commercial system for the most part.

And so, yes, the end goal is, providing as much profit as possible for shareholders.

And that can take very, very terrible turns at times.

I don't know all the details of Ramaswamy's, foray into drug development, but what I do know is that the case of Cassava Sciences is interesting because although their drug proved ultimately to be completely ineffective, it was a vehicle for some shareholders, some company executives to become very wealthy along the way.

And it's particularly painful because of the strong evidence that some of the basic research behind the drug and some of the clinical research testing in humans had been inappropriately or even at times fraudulently represented.

And because of that, the fact that people made millions of dollars, became very wealthy in the development of this drug is, and I think evidence of the waste in our system and the abuse of the system in ways that can be very harmful in delaying progress towards a cure.

But with, the bulk of Alzheimer's research, I think what's pretty interesting to me about it is that because of the dominance of this one way of looking at the disease, the so-called amyloid hypothesis, that amyloid proteins lead to a cascade of biochemical effects in the brain that cause Alzheimer's dementia, because of that, the dominance of that idea for many decades.

You have a situation where that has kind of created a kind of crowding out of other intellectual discourse, other scientific exploration, because it's soaked up most of the money and most of the mindshare, if you will, in the scientific community.

And that, has been deleterious in a couple of ways.

One is that this idea, this hypothesis has not been one that has ever created any drug that can arrest or reverse the symptoms of Alzheimer's disease, even though it has created drugs that have come to market and have had very, very subtle, some would say almost imperceptible benefits and at a great cost, great financial cost, tens of thousands of dollars per person per year, and the possibility of great harm from side effects.

So these combination of factors are very frustrating when you see that other ideas haven't been as well funded.

And the drugs that have come out of it have been frustratingly, meager in their benefits and sometimes very costly.

Is there any maverick in the field right now that shows promise?

That's taking an intellectually divergent perspective on, you know, the chemical equation that's going to cure this in a person?

Yeah, I'm glad you asked that, in part because I'm happy to report that there has been in recent, very recent years, increasing skepticism about the dominance of one way of looking at the disease.

And I think even the skeptics of the amyloid hypothesis would argue that amyloid proteins have something to do with the disease.

They just don't have everything to do with the disease.

They may be an aspect of it, but they may not be the cause and the driver of the disease.

And so a lot of interesting research is going on that I think it's possible that it could illuminate new aspects of how to attack Alzheimer's, or even possibly produce remedies to the disease.

Even in the next few years.

Let me give you a couple of examples.

One is the GLP inhibitors.

These are the, somewhat, magical, you might even say weight loss drugs like wegovy and others that have come to market in the last few years and have revolutionized thinking about obesity and are being considered or used for diabetes and other ailments.

They seem to have a wide range of associated, possibly beneficial, preventive effects for a range of other ailments.

There was a very interesting article in Nature, a prestigious scholarly journal that came out.

I think it was just a few days ago that talked in depth about a study of, patients at the Veterans Administration who had been taking these GLP-1 inhibitors for a considerable period of time.

And there was suggestions that it was, serving to be, at least somewhat effective in preventing even Alzheimer's disease, the rate of Alzheimer's disease in that group of patients.

Now, that's an observational study.

It's hard to know for sure whether that would bear up in further research.

But right now there is a clinical study, a large scale clinical study going on testing GLP-1 inhibitors for their possible benefits among Alzheimer's patients.

I think it's fascinating.

I think it's something I'll be really keeping my eyes closely on.

And if you don't mind, I'd like to mention -two other things that I think, -Absolutely.

I was going to ask you if there's more, there too, alternative approaches.

There are alternative approaches that give me hope.

As someone who has unfortunately been writing a book about some of the many discouraging aspects of the study of this disease, one is there's something called the infection hypothesis of Alzheimer's, and this is the idea that even though there may be several factors to the disease, several reasons why it makes cognition worsen.

One may be infections with viral agents that are kind of latent infections from things like herpes virus that causes cold sores that then resolve.

And then people think, okay, thankfully I'm over this, but those viruses might hang out in some organs in the body, including the brain, possibly for years or even decades, and cause these subsidiary effects, including the possibility of influencing the course of Alzheimer's and there are, again, clinical studies underway now that's exploring whether that might be a factor.

Increasingly that's thought to be one of several factors that's worth serious study, and I'm happy to report it's getting that study.

So, we have the possibility of learning more about it through those clinical experiments.

And finally, let me leave you with sorry to filibuster here.

No, please!

Let me leave you with one last thing, that to me is central to, you know, our place in the world with the unknowns of medical science.

And that is that we have agency in our lives, even in a situation like Alzheimer's, where there is no cure and there's no real surefire preventive, there's no supplement or brain game or set of practices that will ensure that you can't get this disease.

But what we do know is that high blood pressure, high cholesterol, sedentary lifestyles, poor diets, these are all factors that can contribute here to your susceptibility both to Alzheimer's and the worst symptoms at an earlier age.

So by living our best lives, by taking some sense of agency in our destiny, medically, we can at least have a beneficial effect.

And it's going to have a lot of important dividends for your entire life.

And also possibly in forestalling the worst effects of Alzheimer's disease.

In the second alternative example you mentioned, were you using herpes as just an example of, a condition that recurs and that's in the bloodstream, that may be, dormantly, unknowingly, impacting your neurology or biology?

You were merely using that as one example.

The thought is it could be, you know, any one of a myriad of examples.

Is that accurate?

That's right.

It could be other viruses as well.

The reason I used herpes is that it's undergone a higher range and depth of testing and examination than other viruses, and shows some possibility that it could, in the fairly near future, provide some answers.

Understood.

And it has to be so challenging, in the field to look at someone who's aging and look at, all of the factors, in their life that could have contributed to this outcome.

And, you've named some of them, but is there any method to the madness of kind of discriminating against what you could say is symptoms of old age versus symptoms of, dementia, or specifically, as you classify it, Alzheimer's induced dementia?

Yeah.

I mean, I think, I'm not a medical doctor, so I wouldn't want to provide all the particulars of that.

But what I can say is that, it can be difficult to distinguish sometime between, dementia symptoms caused by, different kinds of ailments.

So Alzheimer's is considered by far the most common form of dementia.

And so a lot of people are classified as having Alzheimer's when they might also have other things going on biochemically that could be causing problems.

And, to be as clear as possible.

There are brain scans and there are, cognitive testing, and there is the ability from, of medical doctors who are sophisticated in these kinds of techniques to give patients a really clear sense of what's going on.

It's not a guarantee of how the disease will progress, but it's a way of assessing where people stand.

Understood.

And when you look at the, pending, imminent and active cuts to NIH, CDC, others.

You know, when I would interview people like Tom Frieden, and Nora Valco, and Maria Ferreira, others, whether they were in the Academy, or on the government science side, and when you hear, entrepreneurs interviewed about this, too, it's always funds.

You know, we wish there were more funds.

There just aren't enough funds.

And, part of the reaction to Covid is a demonstration of that and how ill prepared we were to manage it.

What's happening now is sort of seemingly an indictment of a system that is perceived to have been well funded and not delivered enough results, and therefore a bomb has been set to the whole medical infrastructure establishment.

Your perspective on that, as we close here.

Sure, thanks very much for that question, Alexander.

Because it's one that weighs heavily on me.

So I have written a book that is very critical of some of the institutional authorities of science.

And what I mean is the National Institutes of Health, which funds most biomedical research in the country, the Food and Drug Administration, which regulates drug development in our country, universities that oversee a lot of this research and scholarly journals, one of which, Science magazine, I work for, which I'm happy to say is one of the journals that's beginning to take these allegations and evidence of possible fraudulent image doctoring much more seriously.

Let me just say that, these are institutions that I consider to be the gems of scientific development, that they're so important for our system to produce really valuable changes and findings that have increased our lifespan, that have cured or found treatments for all these dreaded diseases.

And let's not make any mistake about it, in my view, cutting their funding criticisms that amount to let's burn it to the ground and restart, that are emanating from some quarters in Washington DC these days, I think are extremely wrongheaded and are exactly the wrong approach.

But it would be hypocritical for me and a terrible mistake for journalists and for scientists who support these agencies to somehow pretend that everything's fine, somehow pretend that they don't have any problems.

These agencies, these institutional authorities, need to up their game.

They need to proceed more with greater...

Understood, and in 30 seconds, and I know this is not a 30 second question, but I want your answer.

Is it more of a substantive, research or marketing problem?

Even you could go to the CDC website and you couldn't see a timetable for curing A, B, or C disease.

Was it a lack of transparent guidance from them that, or do you think, a lack of actually constructive practices, that led us to this point, where we have to accept from the current administration, the message that, this was mismanaged, that these entities have been mismanaged.

These are human endeavors.

There is an enormous amount of mismanagement and, laxity and in my way of thinking, arrogance.

But they are institutions that are very important for society to build up.

They should be well funded.

They should be protected, and they should be, there should be strong demands that they improve their practices to serve us better.

Fair enough, really grateful for your perspective, which is a nuanced and insightful one, Charles.

Charles Piller, author of the book Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.

Thank you again.

Thank you, Alexander.

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