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- [00:00]
Susan Ettlinger
The PC gave us computing power at home, the Internet connected us, and mobile let us do it pretty much anywhere. Now, generative AI lets us communicate with technology in our own language, using our own senses. But figuring it all out when you're living through it is a totally different story. Welcome to Leading the Shift, a new podcast from Microsoft Azure. I'm your host, Susan Ettlinger. In each episode, leaders will share what they're learning to help you navigate all this change with confidence. Please join us, listen and subscribe wherever you get your podcasts.
- [00:31]
Mike Pesca
This episode is brought to you by Progressive Insurance. Fiscally responsible financial geniuses, Monetary magicians. These are things people say about drivers who switch their car insurance to Progressive and save hundreds. Visit progressive.com to see if you could save Progressive Casualty Insurance Company and affiliates. Potential savings will vary. Not available in all states or situations.
- [00:59]
Hi, I'm here to extol the virtues of Peska Plus. Now. Full disclosure, I am Peska and have been accused of being a little plus. But if you subscribe and you do so by going to subscribe mike pesca.com you get all sorts of bonus features. We do extended interviews. We have a book club every other month. We had an amazing live event. I don't know if I'll ever replicate this, but it was a soiree plus a discussion with members of the Fifth Column. And it's free for everyone who is a Pesca plus member. Now is the best time to get your membership approved. I have to tell you the approval process you're going to skate through. I know this because as I said before, I am the titular Pesca of Pesca Plus. And of course, like all of our subscription service services, all the podcasts will be ad free but with Pesca Plus. Oh, so much more. Subscribe Mike Pesca.com It's Friday, March 14, 2025 from Peach Fish Productions. It's the gist. I'm Mike Pesca. When we last left the Senate Democrats on the verge of a government shutdown, according to the Washington Post article I read on the show Wednesday, the group is still agonizing over whether to use this rare point of congressional leverage to extract concessions from Republicans. Disclosure, that wasn't me, it that was the Washington Post. Very nice audio service. Don't know if it's a computer or a guy, but kudos to him. Kudos to the guy, the computer they hired for the Hill. What word do you notice in their coverage?
- [02:33]
Senate Democrats are staring down a major dilemma as they agonize.
- [02:37]
Yeah, and the New York Times wrote about it with these words in lengthy closed door group discussions over the past three days, Senate Democrats have agonized over how to handle the spending bill. Well, friends, the agony is over. Though maybe not for Chuck Schumer. Schumer smart. He doesn't give in to the more impassioned parts of his coalition when it's not in his or their interest. But he's also old and easy to make fun of. And he's going to be, of course, younger members of the coalition, cooler hoodie wearing members, stylistically the opposite of Chuck Schumer, like John Fetterman, or specifically only John Fetterman, have argued against the shutdown as well. Remember what you are voting for, you are voting to shut the government down and that will absolutely punish millions, millions of Americans. And that argument seems sound. I didn't hear a good substantive rebuttal on what would actually happen to people or the government. I heard about messaging or signaling, but not about people. So on Wednesday I pointed out that Democrats shouldn't worry too much about blame, but they should also realize they don't have much to gain. Now, I thought for a while that I had predicted wrong. Axios headline on Wednesday p.m. senate Minority Leader Chuck Schumer has signaled his party is prepared to let the government shut down. Cut to the next day Axios headline Democrats prepared to fold on government shutdown. What happened? Well, the House Democrats and a lot of Senate Democrats are going to blame Chuck Schumer. And I say that is what he wants. I mean, he doesn't want it, but he'll take it. He's going to be their pain sponge. He is saying, you know what? Yell at me, blame me. I'm not up for reelection and when I am, I'll be probably too old and I'm running in New York. Chuck Schumer is quite clearly saying a government shutdown is not the right thing to do, ethically or politically. He explained why to Chris Hayes and.
- [04:41]
Chris Hayes
Donald Trump want a government shutdown so they can take the dramatic cost. Here's why Chris Under a shutdown it is the executive branch, in this case Trump, Musk, Doge and Vogt, who's head of the omb, who we all know are authoritarians, vicious, nasty, who would have sole control over what is funded and what isn't. They get to determine what is a, quote, essential service and they will just cut to smithereens far greater than in the CR bill, which is a lousy bill, far greater than that, what could be funded and what couldn't. And there's no recourse. You can't go to court. This is a decision totally in the executive branch.
- [05:23]
Mike Pesca
The logic is solid. The shutdown would have signaled a willingness to fight, would have messaged that the Democrats aren't going to take this lying down, but it would have actually done the opposite of what they're trying to do for Americans and also politically. And so since messaging and signaling was the major selling point of the shutdown, Schumer is offering them an alternative opportunity to signal their displeasure through him. And that might be the agony. It's not the kind of agony where it's a difficult choice because it's a 5050 call over whether it will help the Democratic agenda. It is a tough choice because it's actually pretty clear what the right call is. Only Schumer knows shows he's going to get slaughtered for it. And that, my friends, that is the political agony on the show today. It is a full show interview with a fascinating figure. So researcher Matthew Schrag is a doctor and also medical researcher of Vanderbilt who is sometimes hired to investigate drugs and studies. And the people who hire him are looking for perhaps flaws in the studies, so called breakthrough drugs that he says, actually, I don't think it's going to break through through and then the companies invest accordingly. Okay, fine. So one day as part of his job, he came across not just a flaw, but one of the biggest actually bordering on frauds in the history of American medical research. The underpinnings of what we knew or thought we knew about Alzheimer's research seemed to be entirely wrong and the product of a lot of bad things like groupthink, assumptions overriding evidence and like I said, flat out fakery. Shrag's story is told in a new book called Doctored. That's where I found out about him. I wanted to have him on himself in his own words to talk about what he found and how he does his job and how he thinks about medicine and truth. Dr. Matthew Schrag of Vanderbilt University. Up next, elevating my style used to mean well spending way too much money and way too much time figuring out what website. Then when you go you say does the sweater look good? But Quince ends all that I know and can rely on high end versatile pieces at prices I can afford. Quince is a delight. To clad myself in the Mongolian cashmere sweaters from $50. The the leather jackets, great pants for every occasion, formal casual pleats non they got it all Quint Items are priced 50 to 80% less than similar brands. The key is they partner with top factories, they cut the cost of the middleman, they pass the savings on to us. I mean, that sounds kind of cliche, but that's what they do and it works and you look good in them. They only work with the factories that use safe, ethical and responsible manufacturing practices and premium fabrics and finishes. I have a Mongolian sweater. That's the one. I have worn it on a few of the videos that we put out so you could see it. You'll never know how good it feels from the inside, but I'm here to tell you it's plenty good. Indulge your affordable luxury. Go to quince.com/the gist for free shipping on your order and a 365 day return. That's Q U I N C e com thegist to get free shipping and 365 day returns. Quince.com the Gist For a limited time.
- [09:00]
Ryan Reynolds
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- [09:31]
Mike Pesca
For over 100 years since Alwa Alzheimer discovered and named the disease that you know is Alzheimer's disease. This is how it was thought to have worked. An amyloid plaque, a sticky plaque in the brain accumulates. There's this tangled protein named a tau within the nerve cells of the brain that's present too. And then the person has to have symptoms of dementia because sometimes people can have physical features and not experience dementia. But when you have all three, it's Alzheimer's. And this is called the amyloid theory. The amyloid plaques being key to understanding what Alzheimer's disease is until. And then for years. Well, for years nothing was done to research it. And then research became very prominent and there was a lot of money riding on it. In fact, companies worth billions of dollars just on the basis of possibly coming up with a cure. And then it all began to crumble because largely of the efforts of my next guest, Dr. Matthew Schrag. He's a neuroscientist and a physician at Vanderbilt University. He is a and this is not a word he likes and we'll explain why he's a whistleblower into the entire apparatus of identifying amyloid plaques. He is the main subject, the hero, if you will, of a new excellent book by the journalist Charles Pillar named Doctored Fraud, Arrogance and Tragedy in the Quest to cure Alzheimer's. Dr. Schrag, welcome to the gist.
- [11:04]
It's my pleasure to be here with you.
- [11:06]
So take me back to when you first started looking into everything that I've been talking about, the imaging, amyloid plaques, et cetera. When was that in your timeline as a physician and researcher?
- [11:19]
Well, I've been studying Alzheimer's disease for the last 10 or 15 years, and I've been studying it from the perspective of a research integrity analyst for about four or five years.
- [11:31]
What's a research integrity analyst do?
- [11:34]
Well, there's some of the same things that we do in the laboratory. You know, a lot of the work in the laboratory is ultimately leads up to taking a photograph of some experiment or another. And those photographs are often the stage at which research integrity lapses enter. The process is how somebody handles or manipulates the, the photo of the end result of an experiment. And so we've become very good in this laboratory and analyzing images and some of those skills cross over into a forensic standpoint to figure out when, try to figure out when data's been altered.
- [12:09]
Are you the internal affairs of the scientific community? Like the cops have their ia.
- [12:14]
No, not at all. I'm just, I'm just a scientist running a lab and occasionally have, have worked as a consultant for journals or, or attorneys or had concerns in this area.
- [12:26]
Right. So sometimes there is monetary, there's money at stake. I think in this case some short sellers were questioning the, a drug which was said to be a blockbuster drug, and they hire you to look at it. So you're the guy who can point some, or raise some red flags, is that right?
- [12:44]
That's right. So this case involved a company called Cassava Sciences, which was a relatively small biotech company out of Austin, Texas, who were developing a drug that they thought might be helpful for Alzheimer's disease. And a number of individuals had some preliminary findings suggesting that they, they were worried that the data might have been manipulated. And they asked me to come in and verify their concerns and extend the research and help them to draft a report describing the problems. And it turned out in, in my opinion anyway, that they were right, that they were just enormity of red flags in the data associated with this company.
- [13:21]
And this drug, and this drug is Simufilam. Or was.
- [13:25]
That's right, yeah.
- [13:26]
And so when we said billions of dollars are rioting on even the promise of the drug, I think based in large part on your research and the fact that the short sellers were correct, that there should have been red flags, they lost something like $5 billion in market cap, I think.
- [13:42]
Yeah. The company did relatively poorly after this information became public. And then ultimately the clinical trial that they were running failed, which is a sort of anticipated result when the data that supports the. It's basically the underpinning of doing that trial is perhaps not trustworthy.
- [14:00]
Yes. So what you do is not necessarily. There are many kinds of scientists who look at data sets and say, oh, that seems to be an anomalous reporting of the findings. But you're actually looking at images, right?
- [14:13]
Pictures, for the most part. Yeah.
- [14:15]
Because these amloid explain it to us as if. I don't know, me, I wasn't familiar with what an amyloid plaque should look like and what.
- [14:24]
Sure.
- [14:24]
What they're looking for when they're finding the telltale. Oh, I believe it's amyloid beta star 56.
- [14:30]
Well, the star 56 story is sort of tangential to cassava Science's story, but it came out of this. This work. I was working on this case and we were working on some techniques to try to improve our ability to measure the differences. It's one thing to say that looks like the data's been fiddled with. It's another thing to try to prove the point or to put some probabilities around the point. And so we were working on those techniques when we encountered this second set of potentially problematic data. But the story of the amyloid cascade hypothesis goes something like this, and you set it up very nicely. We've got 120 years of knowing that plaques form in the brain in Alzheimer's disease. And coming out of the genetic revolution of the late 80s and early 90s, a number of genes were discovered that were linked to Alzheimer's disease. These are very rare variants of Alzheimer's disease that run in families. Most Alzheimer's disease doesn't track in families quite that cleanly, but there are exceptions. And in those families, the genes seem to be closely linked to this protein, beta amyloid. And because genetics were so dominant at the time this became the leading theory was that the plaques came first. Everything else that happened in the brain was downstream, essentially of the plaques was caused by the plaques. And the argument was, you've got this core disease driver, this beta amyloid plaque, and you've gotta either get it out of the brain or you've gotta block its effects or prevent it from forming in the first place. And those ideas have formed the basis of the therapeutic strategies for the various clinical trials that have come since then. So around the year 2000, there was a very high profile clinical trial, probably the most effective up until that point, of remov removing the plaques. And what they did was extremely clever. They vaccinated patients against that little protein and tried to get the body's immune system to gobble up and remove the plaques. And they were somewhat successful at doing that. But they had a couple of problems. One is that some patients got side effects, the brain would get inflamed, and so they couldn't continue that trial. But even in the patients who had plaque removal, they didn't seem to get better. And that set up sort of the first big controversy around this hypothesis. And the idea sort of took a big stumble and people started criticizing it.
- [16:44]
So was what you were doing going back and questioning, is it really the amyloid beta 56 or were you looking at something else?
- [16:53]
Well, so the A beta 56 came on the scene right after this clinical trial came along. There's a group of researchers who started with this line of thought, okay, if the plaques themselves aren't the problem, is there some sort of reformulation of this idea that could help us figure out where to target the treatments? Maybe, you know, when you form a plaque, it's this massive clump of these proteins, just millions and millions of copies of this protein all stuck together. And somewhere between an individual strand of this protein floating around in the fluid of the brain, in this massive clump, there must be a whole range of individual size clumps that are much smaller. And they said, maybe there's some toxic component in that spectrum. And basically what they argued was what they thought they found was that a clump of 12 strands of this little tiny protein was the toxic magic bullet, that when it clumped it at a particular size in a particular way, that was the toxic piece that caused memory problems. And they argued that you could just go after that. That was the A beta 56. It was the big reformulation of the idea of the amyloid cascade hypothesis.
- [17:57]
Were the original drugs taking neutralizing all of the amyloid plaque, including this particular beta? If they were sweeping it all up, why wouldn't we have seen an effect of, you know, curing or reversing dementia?
- [18:12]
Yeah, well, I think that you've got two issues there. One is that you're unlikely to sweep it all up. And so if you're. If you're removing 50% of the plaque, but only a teeny tiny fraction is actually the poisonous component.
- [18:23]
So the story is something like, okay, the original drugs weren't effective enough because they weren't sufficiently targeted. But now that we know what the real thing we have to target is, we can make drugs that are more effective.
- [18:33]
That's right. And variations on this theme were developed. People came out and said, okay, maybe not. It's. Maybe it's not a strand, you know, a clump of 12 strands, maybe it's three or four, a particular modified version. But this sort of set the stage for reformulating the idea to target specific smaller clumps of beta amyloid that people have gone on to call oligomers, which just means small clump.
- [18:54]
Great for you scientists. That's great for us laymans, like, oh, another confusing term on top of a confusing term. But that's fine.
- [19:01]
I'm sorry about that. I'd say half of our prestige in this industry is just the language you use, right?
- [19:07]
Oh, yeah. All the hard sciences, soft sciences, poetry. Absolutely. So what did you do? What did you look at? Or what did you reexamine?
- [19:17]
So this group published their findings in nature in 2006. It was a huge.
- [19:21]
And that's big. That's as big and prestigious a journal.
- [19:24]
As it gets, basically. As big as it gets, yep. And it was hugely influential. It was not just in Nature, but it went on to be cited an enormous number of times and continued. In fact, I would say continues to be cited. It's an influential paper.
- [19:37]
Seems like 1900 times.
- [19:39]
Charles writes it. Just enormous amount of attention. What I found was that initially some other papers written by this team of authors had some red flags that they happened to be in a pool of papers that we were practicing on for this other case, but it was the same authors. And when you start to see patterns, when you see issues, come up with a group of authors, the odds of seeing it throughout their work are pretty high. And so eventually we saw, or I saw enough papers with problems that I thought, well, we better look at this group. And this Nature paper was part of the resume from this group that needed attention.
- [20:15]
You found a group of authors that correlated to papers with questionable results. In other words, you identified your clump of toxins.
- [20:25]
Yeah, I mean, if there's one pattern in this business that has proven to be remarkably reliable, it's that cheater's cheat. And when you find a couple of problems, and they're legitimate problems, and not just mistakes. The odds of going on and finding a lot more of that are pretty high.
- [20:41]
Yeah, but my point there was just to point out what they were doing or said they were doing, which is to find the telltale toxins within the overall body of work. That's exactly what you were doing. But your toxins were people, not beta proteins.
- [20:56]
That's an interesting descriptor. Yep. Well, and I have to say, this high profile paper, when we went through the forensics for it, there were problems in the majority of the figures. They sort of copy paste type changes. So sometimes you'd see little clone segments within an image where there were repetitive features and it looked like somebody had covered something up or added something into the image.
- [21:17]
So I want to stop you. This is really interesting. What you're doing is you're looking and you're magnifying to an amazing degree. You're looking at the pixels, you're looking at the visuals. And the nature of their fakery was they would take these visuals and there was, you know, the beta that they wanted to say was everywhere, maybe wouldn't be everywhere. So they'd cut and paste and they'd use this protein and give the impression that this protein was prevalent when in fact it wasn't. It was a forgery. Right, right.
- [21:58]
You know, we would see the same image used in two different sections of the, the manuscript. And one, one it's describing mice that are much younger than at another time when they're describing it. And so you can see how the data in that set of figures had been altered and altered in sort of a directional way. Right. And that's one of the key things.
- [22:16]
Yeah, right. It wasn't just random mistakes. It would always to prove the thesis.
- [22:20]
That's one of the key things that we're looking for is when we, when we say this is very likely to, to be manip error, we're looking for more complex changes. We're looking for things that are hard to imagine just happening. Somebody grabbed the wrong file or wasn't paying attention because you know that's, that's just real life. That stuff happens, but like it's directional.
- [22:40]
Does your skill lay in your eye? To some extent, especially back then. Maybe we talk about if AI is now getting involved. Yeah, but you're just able to notice this, whereas others aren't. Like an expert on art forgery.
- [22:54]
I think some of it is going into it saying, I'm looking for that. When we peer review a paper, most of us don't start from the point of Saying this person could be a fraud, that's just not the way we're wired, nor probably should we. And so people often ask, well, why didn't the peer reviewers catch it? And I think if something is really ham fisted, peer reviewers can and do catch them. But that's not peer reviewers primary job. Their job is to think about the science and does this make sense and are the experiments reasonable? They're not really forensic specialists.
- [23:26]
And so look, it's so interesting that you're looking at it and years earlier, maybe they didn't have, you tell me, did they not have the magnification tools for someone to sufficiently suss this out.
- [23:37]
With, you know, they probably did. But if you look at images from the mid-2000s that had been photoshopped, I mean, we probably thought they looked pretty clever when we were doing that kind of stuff back then. Right. I mean, when we were playing with these tools and now they look relatively primitive. And I wonder to what degree we're going to have the same reaction to AI generated images that things to us that look pretty impressive and convincing that 10 or 15 years from now we'll look back and say, I can tell that that came out of a box.
- [24:05]
Like the first Star wars movie, you know, had to be.
- [24:08]
Oh, it was amazing.
- [24:08]
Right? Yeah, right.
- [24:10]
Absolutely right.
- [24:12]
I wanted to ask you something about the image. Oh, would most research. I'm sure there are all different kinds of researchers and they read the study and try and glean different things from it. But do most researchers in reading an original study, I'm not talking about the people who are in charge of peer reviewing it, but the experts who look at it, who the equivalent to a research based on data, they might have inclinations or suppositions about the data. It might be surprising sometimes if the data shows a finding that's, you know, so extreme. That's with data. Yeah, but my question is with pictures. Are they literally looking at the pictures? Would they be looking at the journal Nature? I'm picturing it in print and like kind of holding it up to the light and seeing if the plaques look like what the researchers say the plaque looks like.
- [24:59]
Yeah, probably not in that level of detail, but it is interesting when the story comes out. All of a sudden you have this veritable parade of people coming forward saying, could never get that to work. We had tons of doubts about this, but because, and I'm sort of intuiting here what happened, but this was an incredibly prominent lab and this was a finding that I think a group of People really wanted. Right. It sort of fit sort of the missing puzzle piece at just the right time. And again, it went through iterations after that.
- [25:31]
It rehabilitated a prominent theory that a lot of people and a lot of money were invested.
- [25:37]
So to stand up and say, I couldn't show that, you know, it was a somewhat risky thing to say. And I wonder to what degree that contributed to its longevity in the literature, because literally the minute the story came out, there was a parade of people saying, we couldn't get that to work. And, you know, Dennis Selko, who was one of the original authors of the, of the amyloid hypothesis, came out and said that there were components of the methodology that just didn't make sense to him and that he had always had those doubts. And so there had been sort of this long running a stream of doubts that sort of didn't rise to, you know, to the level where everybody knew about it.
- [26:13]
Yeah. So everyone pointed to that study, or so many people pointed to that study. And I'm sure there were still some dead enders who said, no, it's right. But they pointed to it and they essentially tried to sequester. Sequester it. Right. And cauterized the wound and say, okay, take this study out of circulation or out of the body of knowledge. We're still.
- [26:34]
We're still fine.
- [26:34]
Yeah, but they weren't.
- [26:36]
Yeah.
- [26:37]
So that now, now, now we get into human nature and what people are invested in. These aren't people consciously making dedicated to fraud, but they are contributing to something other than the truth. And in fact, a giant distraction. What do you think explains that?
- [26:55]
Well, I think you've got a couple of tiers of issues here that are interacting with each other. You know, the first thing is it's not just one paper. Right. There's one big, massively influential paper, but we're actually talking about a larger body of work. So this specific group, you know, had maybe about 20 papers where we found really serious issues, and collectively, they have a fair amount of influence. But then also those papers are amplified in the, what we call narrative review literature. People write articles where they try to build theories and these ideas are integrated into those big theories that go on to guide the field. And so even though people had expressed some doubts privately or in some cases quietly, publicly, they still went on to cite these papers. It was sort of a useful component of building the foundation of this argument. So that was one big piece. The next big piece is actually that, that the clinical trials were really not aligning with this idea. But there was this reluctance to accept the biology of what the clinical trials were telling us. As people develop antibodies to go and bind up these specific oligomers of various persuasions over and over and over again, we were getting poor outcomes. We were removing plaque, we were removing certain forms of beta amyloid. But patients were not getting better, they were not declining more slowly. And even in the late last couple of years when we've seen a few drugs get approved, we're not seeing the effects at a scale where it's going to matter to patients. Right. So when these new reports came out for two drugs in particular, that Aduhelm is that one, Aduhelm was the first and extremely controversial. And there have been two since then, Lecanemab and Donanemab, which are slightly less controversial. But these were the most effective drugs on the market. And we gave them as a field, we. As a field, I wasn't involved in it. But when they were given to patients at a very, very early stage of Alzheimer's disease and they were carefully selected to make sure they had loads of beta amyloid in their brain, so everything is right. They slowed the progression of Alzheimer's disease by the just slimmest of margins, a margin that most patients couldn't perceive. And so conceptually, this is showing us that the plaques are just not the big driver that we thought they were. Right. We're sort of at the end of this process. There's probably some role for plaques in what's going on in the brain, but it's not this big massive factor that's going to be a game changer in the pursuit of a real treatment for Alzheimer's disease.
- [29:26]
And we'll be back in a minute with more of Dr. Matthew Schrag.
- [29:38]
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- [30:08]
Darwin
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- [30:42]
Mike Pesca
Dr. Matthew Schrag of Vanderbilt University, essentially the protagonist of the new book Doctored. All the money spent on trying to target the plaques is that money that could have been spent looking for other cures, finding other cures? I know you talk about some of the other possibilities.
- [31:01]
Yeah, it's certainly an argument, right. And there, there are people who have been in this space for decades who have said we just can't get traction unless you genuflect to this idea that the beta amyloid plaque is supreme, that this is the first domino in the cascade. If you think that smoldering inflammation is the problem, you've somehow got to put it downstream of beta amyloid or you're going to have a hard time getting funded. And so people have sort of contorted their ideas, or at least that's the description many people have brought, you know, about their experience, is that they had to conform to this architecture, this cognitive architecture around what was going on in Alzheimer's disease.
- [31:38]
So there were people who had strong inclinations, intuitions, it might be something else, but either they knew where the money was or I always, this is always my description for these things. There's a great social pressure. You don't want to be seen as, you know, the nutter who throws away amyloid theory, which quote everyone knows about and focuses on inflammation, you know, that marks you as a certain kind of person and doesn't get you invited to certain, if not cocktail parties than text threads, right?
- [32:08]
No, that's exactly right. I think that, you know, there's some, some ways of thinking about science in general that couldn't benefit from the experience we've had in the Alzheimer's field. And that's that even when you've got a dominant hypothesis, even if it's right, let's say that the amoled hypothesis was completely right. Permitting a broader range of ideas to compete with it is going to strengthen that idea. Right. I think that if you get a really monolithic field and you only fund one concept, you can create an echo chamber where these sorts of problems, like research integrity issues cannot get rooted out quite as fast. If there's competition, right. People are going to say, no, no, no, that's wrong. Right. And it's going to get Those ideas thoroughly tested faster. And so even if the leading hypothesis was right, you still need to permit some of the nutters to be part of the conversation.
- [32:57]
Yeah, maybe don't even call them nutters.
- [33:00]
There you go.
- [33:01]
But let's go back to when I think the science article that you first appeared in, but that Charles Piller wrote was in 2021. And it's not as if. And then there was some testing and some debating, but every single. Every single thorough vetting of what you were saying just backed you up. You kept being right because you were right. It took a long time, and it's still going on to unwind from those incorrect conclusions. How long did it take? Why did it take that long? And do you think that there. Well, then we'll get into what could be done better or the legitimacy of the criticism.
- [33:42]
And I have to preface this by saying that in my experience, Nature is one of the most responsive journals out there. Right. And so when we criticize how long it took. Right. That's funny. When we criticize how long it took, understand that a lot of journals have done a lot worse than this. And so the paper was ultimately retracted only about six months ago. And really we didn't see motion on that until we won.
- [34:05]
Five years after. Five years after you were reading it.
- [34:07]
Darwin
Yes.
- [34:07]
Mike Pesca
Three and a half, four, anyway. But we didn't see action, at least public action, until the majority of the authors were on board with it. Right. You really had to win over the authors to see this. I think what would surprise most people is that when you have a serious research integrity problem, I think most people are surprised by who's responsible for investigating that. Who do you suppose it is? Well, it's not the nih, it's not Health and Human Services, although they have a role.
- [34:37]
Almost all licensing body should be implicated, you would think.
- [34:41]
The investigation is almost always referred back to the parent institution. So the University of Minnesota is asked to investigate their own people. And of course, the University of Minnesota benefits from indirect funds coming in from the grants that fund these people. They share a reputational interest in potentially not finding problems.
- [35:00]
It's a disincentivized body to actually fund, find fault that. That would be it. Yeah.
- [35:04]
This is in, in some ways potentially the most conflicted imaginable system. And almost all the other steps in the process often, often wait for the conclusion of that investigation, which can take years and years and years. And so many journals will simply take your concerns and say, we're going to sit tight until we hear from the University of Minnesota, what they think happened, which may never happen.
- [35:29]
I suppose that. But I guess you can make the argument that that is thorough and you don't want to incorrectly ruin someone's career. But sometimes, you know, justice delayed is justice denied. But I'm worrying about all the. Or wondering about all the other research that's going on based on these false assumptions that a timely and perhaps more fairly conducted investigation would have redirected. Right. Would have. The science would benefit if we know who's telling the truth. And we know that in a time.
- [36:01]
Well, look, there's a couple of things that are crystal clear, is that when there are issues of a substantial magnitude, institutions can't investigate themselves. It doesn't make sense. Right. That simply shouldn't happen. There should be an independent body appointed to do this fairly and efficiently. And you're absolutely right that some people who are accused ultimately get cleared of those accusations. And they also deserve to have their reputations cleared reasonably quickly after an appropriate investigation. And so, you know, all parties are served best by doing this in a fair and efficient manner. You know, there's a. One of my colleagues commented that the culture of research integrity investigations is innocent until retirement, not innocent until proven guilty. Right. You just sort of drag your feet until these issues go away.
- [36:46]
Yeah, yeah. Until tenure gives you your pension. There is, it seems, the evidence points to. There was one researcher who was consciously faking.
- [37:01]
That's right.
- [37:02]
And there were more prominent researchers who this one researcher worked for who might have been snookered, but also afterwards weren't exactly quick to correct misinformations. And this one researcher, French neuroscientist affiliated with the University of Minnesota, Sylvain Lesney, just so your paper comes out like we say, in 2021. Last month, February 10th, I'm reading this report from Science that he has resigned. It took that long. And which isn't to say he's now not a scientist anymore. He just left that institution.
- [37:38]
Yeah. This is problematic. Right. I mean, it just. There is this sense of lethargy and how these issues are handled, and I think a sense of not realizing how important they are. When people have criticized the work that I have done and that Charlie has written about. One of the most common criticisms that we get is not that the forensics are wrong or that the problems are not, in fact, problems, but that we're painting with too big of a brush, that this hasn't really influenced the entire field. That's sort of the most typical criticism. But I think that this is the bigger part. This is the part that influences the entire field. They're right. It's a relatively small number of people who are involved in outright fraud, particularly of a quasi criminal nature. Right. This scale is relatively rare. It's not as rare as we'd like to think it is, but it's relatively rare.
- [38:27]
By the way, quasi criminal. Right. One of the main researchers in one of those drugs that we talked about, he was convicted of crime.
- [38:33]
Well, he's been charged. That's right. Okay, I'm sorry. The invest the case is still ongoing is my understanding. But at any rate, I think that the bigger problem is that the field has a tendency to cover for these sorts of things. The journals have a tendency to allow people to correct things which a lot of us interpret as fake. It better you come back and give people who have been caught in the act a chance to go and do the same thing better. Seems to me to be a poorly rationalized response to these types of problems. But it's everywhere. This occurs with enormous frequency that these sorts of problems are simply corrected. And I think that journals often dismiss the problems. We've worked with a number of journal editors who were hugely conflicted in the Cassava Sciences case. There was one journal editor who handled one of our concerns who had actually co authored a paper with the author of the paper we were worried about. And that paper that they wrote together was shortly after retracted for the same stuff. And so this journal editor is telling us, this journal group of journal editors saying there's nothing wrong with this paper, nothing to see here while they're co authoring papers with this other person. And interestingly, that paper was peer reviewed in an alarmingly fast seven days, which I don't know how, how oriented people are to this, but I've never had a paper peer reviewed in seven days. It's extraordinarily fast, right? Ordinarily this takes lightning fast.
- [40:03]
Darwin
Peer review.
- [40:03]
Mike Pesca
This is a month would be fast.
- [40:06]
There are organizations, they're definitely not as deeply funded or as entrenched in the establishment as the journal Science and the universities. But there's Retraction Watch, which you've written for. There's. Is it called Data Colada, which is looking a lot at the social sciences. There's this group that seems to be some sort of open source or the equivalent of a Reddit group that does what you do. They look at, they look at medical imaging to see if anything's been faked. How useful are they? They are symbolically useful, but are they really causing a real retrenchment or reconsideration in the field?
- [40:49]
I think so. I mean, I think it's starting, you know, and it's interesting because you have this sort of loosely affiliated group of people with different levels of expertise and different levels of, shall I say, politeness in their interactions with people. And so there has been some criticisms of how aggressive some of the folks working on Pub Peer are, but I think as a whole, generally they're more right than we'd like to think they are. They have uncovered a lot, lot of problems and I think that there can be a healthy conversation about what's the best way of going about this. But frankly, when journals don't want to hear this, when institutions don't want to hear this, you need a venue where you can have these conversations openly. And, you know, places like Pub Peer have provided that. And, you know, I'll be, I'll be honest that there are certainly occasions where the conversations are not as genteel as maybe they could be, but at least we're having the conversations.
- [41:48]
Is the replication crisis which is going on or has gone on in the, the social sciences, so many experiments just can't be replicated. Is a version of that happening in medical science and the hard sciences?
- [42:01]
Oh, absolutely, absolutely. We have a massive replication crisis throughout the hard sciences and I think that research integrity is a part of that. It's not the whole story. I think there's lots of reasons why we have a replication crisis, but yeah, it's a huge, huge problem for our field and we're going to have to think very, very carefully about how we invest in strengthening the rigor and reproducibility of our, of our data output.
- [42:28]
Dr. Matthew Schrag is a physician and neuroscientist at Vanderbilt University and he's the main character, I'd say the protagonist of a new book by Char Charles Pillar called Doctored Fraud, Arrogance and Tragedy in the Quest to Cure Alzheimer's. Thank you so much, Dr. Schrag.
- [42:48]
It's been an absolute pleasure. Thanks for having me.
- [42:55]
That's it for today's show. The Gist is produced by Cory Wara, cbso Michelle Pesca. Leo Baum is our intern. Umparu G. Peru Duparu. And thanks for listening.
- [43:13]
Darwin
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