Dr. Matthew Schrag s discovery that one of the most influential studies in Alzheimer s research may have been a fraud has caused headlines around the world. And if that turns out to be true, it means about a billion dollars in U.S. taxpayer-funded research over the past 16 years may be for nothing.
00:50:57.900And then this important study entered the breach.
00:51:02.460This was the 2006 study in Nature, which, as many listeners may know, is one of the most important scientific journals.
00:51:10.420And this study by Lesney and Ash seemed to show a cause and effect relationship showing neurocognitive impacts, memory problems in rats associated with their star 56 protein.
00:51:27.800And so for the first time, there was a substance that seemed to directly cause effects in an animal that mimicked Alzheimer's disease and gave a lot of credence and hope to people who had been believing all along that this discovery would be made and that the amyloid hypothesis would be proved out in a very practical way that would present new targets for drugs that would be able to cure the disease eventually.
00:52:20.740Scientists who advance other potential Alzheimer's causes, such as immune dysfunction or inflammation, complain they've been sidelined by the amyloid mafia.
00:52:34.640Forsyth, the doctor I mentioned a second ago, says the amyloid, I mean, hypothesis became the scientific equivalent of basically the model of the solar system in which the sun and planets rotate around the earth.
00:52:48.100And people had started wondering by 2006 whether the field needed a reset.
00:53:19.120Well, so, yes, I think in fairness to Lesney, he does deserve an opportunity to defend his work during an investigation being conducted by the university.
00:53:29.380I hope that will be a rapid and thorough investigation.
00:53:33.380My fear, and I think it's supported by the experience of many other investigations by universities and other entities with vested interests in a particular outcome, is that it won't be thorough and fast.
00:53:46.320But I think we need to hold out the possibility that the university will get to the bottom of this.
00:53:52.720So I think Lesney deserves his opportunity to defend himself, and I presume he is doing so in the university's look.
00:54:01.080But let's take it a step back to the evolution of Lesney himself as a scientist.
00:54:07.480So I was very curious about this idea that he was the guy who was responsible for all this, as Karen Ash now seems to be implying, or in some cases, almost openly saying.
00:54:21.260And I think what I wanted to do was to ask myself the question, how far back did these concerns with Lesney's work go?
00:54:30.520And Matt Schrag had looked at papers that go back a couple of decades, and others, including Elizabeth Vick, who reviewed some of Lesney's even earlier work, found additional problems.
00:54:44.920So we had more than 20 papers going back a couple of decades where it seemed that there were anomaly after anomaly, question after question.
00:54:55.360And that sort of a history certainly does raise eyebrows.
00:55:00.180But to me, the acid test was talking to one of his mentors at the University of Cannes in Normandy, France, where he did his PhD training.
00:55:09.740And this particular professor, he said that he was doing a joint paper with Lesney back in his PhD days, 2002 approximately.
00:55:22.360And he found images that Lesney had been producing in service of that paper that he regarded as suspect, untrustworthy.
00:55:32.180He tried to have those images repeated by other graduate students.
00:55:38.760So finally, this professor pulled the paper, which was about to be published in a prestigious journal.
00:55:44.700And he pulled it because he feared that would affect his own scientific integrity as the senior author of the paper.
00:55:50.880So I guess what I'm saying is that there had been a history of suspicion, a history of concern.
00:55:58.180And in the field, he became known as someone who had the ability to get things done in the lab that some others were not able to do.
00:56:08.400He was a brilliant bench scientist, they call it, who was able to complete experiments in ways that others found very difficult to do or could not accomplish.
00:56:18.780And when you have that combination of history of difficult to prove images that appear to have been doctored and suspicion from his own mentor in France,
00:56:32.380and this idea that he had kind of the ability to get things done in the lab that others could not accomplish.
00:56:40.400And then you have image after image and paper after paper that is suspect.
00:56:44.740Well, that paints a picture of someone who, you know, maybe has been engaging in possible misconduct for a long time.
00:56:52.880I think people have looked at this sort of activity in science or really in other fields is that it rarely occurs just once in one image.
00:57:07.620I mean, he just loves he's got the same little perfect 365 app on his phone, except he's putting scientific data in there instead of noses and butts and legs.
00:57:18.500Sorry, Charles, that's my level of trying to bring the story to the viewers.
00:57:21.920But seriously, if this is true, this guy's got a massive problem and he's got a lot to answer for, but seems to be going the other way.
00:57:32.060According to your piece, not only did he become the leader of the University of Minnesota's neuroscience graduate program prior to this.
00:57:39.880This is two years ago, but he's leading their neuroscience graduate program.
00:57:43.920It's a respected program, respected university.
00:57:46.200If this guy did all this, that should end.
00:57:48.340And tell us what happened in May 2022, four months after Dr. Schrag delivered his concerns to the NIH.
00:57:59.040Yes, that is a kind of a befuddling aspect to this whole strange story.
00:58:05.840And in May of this year, he received what is called an R01 grant.
00:58:12.060So this is a prestigious, important grant from the university, very competitive to get these grants.
00:58:18.340It can give him up to five years of funding for his work.
00:58:23.120And this was, as you say, months after the agency knew that his work was under a cloud, that years and years of his studies were being suspected for possible manipulation and scientific misconduct.
00:58:38.460So that's question number one about the NIH's action.
00:58:41.400I would add that there's another strange twist to this NIH grant story, which is that the grant administrator for Dr. Lesney for his new grant is a guy by the name of Austin Yang, who is himself a respected scientist and was a co-author of the 2006 study in Nature, this very important influential study that is now under a cloud.
00:59:06.480That that that is not OK. You know, these conflicts of interest are all over the place.
00:59:12.000By the way, what what if any connection does Francis Collins at the NIH have to this story?
00:59:20.300OK, just wondering, because his name obviously has been in the news so much.
00:59:23.320What what what about that? Because, you know, there are a lot of people in the country who have a lot less faith in institutions like the NIH in the wake of all the covid madness than they used to.
00:59:34.620And, you know, this is not going to help this.
00:59:39.360What are people to make of our lead medical institutions within the government and the faith that we should be placing in them?
00:59:47.480Well, let me say that the NIH is so enormously important to our country, so enormously important to curing diseases and to understanding more fundamentally the nature of the bioscience behind many of the dread illnesses that that are being explored by physicians and scientists all over the world.
01:00:10.760So I have nothing but praise for much of the work that IH does now as an investigative reporter, I have looked at federal agencies, including the Food and Drug Administration and the National Institutes of Health when there are possible lapses or concerns associated with how they administer their programs.
01:00:31.100And so like any big bureaucracy, like any human endeavor, there's going to be questions.
01:00:37.140There's going to be lapses in judgment at times.
01:00:41.660There's going to be conflicts of interest.
01:00:43.840And I think it doesn't invalidate the enormously important body of work that the agency has funded over the years, of course, including work in Alzheimer's disease.
01:00:54.220But it does raise an interesting question about whether there should be a reexamination of how they prioritize this work, whether they became, in a sense, what some scientists might call captive to certain interests.
01:01:09.060Because, again, it's been described as the amyloid mafia in this case.
01:01:13.100I'm not saying that the amyloid hypothesis is useless or is somehow disproved.
01:01:19.920What I'm saying is that when you have a situation where year after year, drug after drug has failed when targeting amyloid plaques, that it's worth asking, is the priority on that?
01:01:34.600Where the enormous proportion of the amyloid hypothesis is focused directly on the amyloid hypothesis and on enormous billions of dollars of pharma company drug development efforts are focused on that.
01:01:51.020It's worth asking the question, should there be a shift in priorities or at least a broadening of interest in this, especially in light of what we've seen with the Lesney-Ash situation, where some of the key research supporting that hypothesis has been found to be deeply suspect?
01:02:08.520Well, I mean, and that's the thing. I mean, these poor families out there suffering with Alzheimer's now waiting for the next drug to come through the pipeline.
01:02:17.080The disappointment of Adjahelm, you know, the drug we talked about earlier that did get FDA approval, but $57,000 a year, $56,000 a year flopped because there doesn't appear that it was doing what they had said it would do.
01:02:33.360And then now we've got some euphilim who, you know, which we discussed with the doctor, very concerned about that one, too.
01:02:41.900And I'm sure there's others that are being researched right now, maybe in part in the green apple lane, you know, maybe in part based on this research.
01:02:50.740So what does this mean for families who are waiting for the breakthrough?
01:02:57.280Well, I would say this is a terribly sad situation, according to experts with whom I've spoken, that really what we're talking about is opportunity costs.
01:03:06.640So if you're focusing so much of your effort and so much of your money on a particular scientific direction that has failed over and over,
01:03:16.100then to the neglect of other ideas that themselves could have some possible benefit and could be fruitful and leading to potential remedies for Alzheimer's disease,
01:03:29.520I think the patients and their loved ones have reason to be concerned and have reason to be angry that this occurred and that these suspect studies have proved to be so influential.
01:03:42.620Now, that said, I would say that to me, one of the acid tests for me was talking to a really eminent scientist by the name of Dennis Selko,
01:03:56.740who's at Harvard University and is a progenitor of the amyloid hypothesis and someone who believes deeply in the importance of studying the amyloid oligomers that Dr. Schrag had mentioned in his segment.
01:04:12.620That these are the subtype of amyloid proteins that are thought to be toxic and to be perhaps instrumental in Alzheimer's disease.
01:04:21.560So Dr. Selko said to me that there are currently clinical trials of drugs that are attacking these oligomer types of amyloid proteins.
01:04:38.000And if they fail, the amyloid hypothesis is under some duress.
01:04:42.800Now, that was pretty interesting to me because this is a guy who is a total advocate for this hypothesis,
01:04:49.060believes deeply in its importance, and has spent a lot of his career studying how best to get at it.
01:04:55.340Yeah, the NIH spent about $1.6 billion on projects that mention amyloids in this fiscal year.
01:05:06.720That's about half of its overall Alzheimer's funding.
01:05:10.160So we'll see whether we'll see whether this shakes that or opens up funding in the other lanes and leads to a realistic reassessment of this paper and others like it,
01:05:22.460in which this guy Lesney has had any connection.
01:05:26.000Charles Piller, I hope you win all sorts of awards for this article.
01:05:29.120It was brave and it was important, and I encourage the audience to read it because Charles actually does a great job of walking you through it.
01:06:36.540This is actually part of a much bigger problem.
01:06:39.360So we are all witnessing the Titanic, that is mainstream medicine, going down because it has rammed into the iceberg of chronic illnesses.
01:06:53.740And I'm talking about Alzheimer's, Lou Gehrig's disease, frontotemporal dementia, Lewy body disease, on and on, CBD, PSP, all these other ones, and including late stage cancers, including chronic renal failure.
01:07:09.300We are all in an era in which mainstream medicine is treating things the way we treated them in the 20th century, simple illnesses, viral illnesses, bacterial illnesses, things like that.
01:07:23.400And so we're ending up with things where the big problem here is really about what Alzheimer's is.
01:07:30.240And let me just for one moment say, yes, I've known Professor Ash for 40 years.
01:07:35.100She is a brilliant scientist, a brilliant neurologist, and she's absolutely committed to finding the mechanisms underlying Alzheimer's disease.
01:07:45.960And the work that she did, you did a beautiful job with Charles Piller and with Dr. Schragge, but didn't mention that this is based on an analogy with Nobel Prize winning work.
01:08:00.100And this was from Professor Stan Prusner, that identified in the case of prion diseases, this is a different kind of neurodegenerative disease, looks a little like Alzheimer's, typically faster than Alzheimer's disease and much more rare.
01:08:15.820And he found one form of a protein that is normal, and one form that's abnormal, and if you give the abnormal one, the person or the animal gets the disease.
01:08:27.820So this was an analogy here, which I think is one of the reasons that it was, you know, interesting to people at the beginning.
01:08:34.520Aha, we have the same story, makes sense.
01:08:37.580But as you've shown beautifully, this is much more complex.
01:08:41.540And I should add, you mentioned the green apples.
01:08:45.820In this case, this is a brew, this stuff, this stuff interchanges.
01:08:50.180So you have green apples, red apples, and yellow apples, and they're changing into each other.
01:08:54.900You have larger apples, smaller apples, you have apples that are sticking to each other, just like heated gummy bears.
01:09:00.860So you've got this brew, and it's not simple.
01:09:04.640And they're trying to say, is there one part of this brew that is actually causing the disease?
01:09:10.940And you mentioned Professor Selko, who was really the first, many, many years ago, to argue that it was assemblies of small numbers of these amyloid molecules that were the critical players.
01:10:22.840When you put $40 billion into developing these things and trialing them, it's hard to say, you know, this has really failed.
01:10:30.240But the surprise was that the FDA actually approved this, when in fact, the trial proved just the opposite of what the reason that they approved this.
01:10:42.080They approved it because they said, well, it removes amyloid.
01:10:45.100So we expect it to have clinical benefit.
01:10:47.920No, that's exactly what all of these trials showed is not the case.
01:10:52.100When you remove the amyloid, it does not give you clinical benefit.
01:10:56.700So we're left with we need a better understanding of this disease.
01:11:01.940It just it's so undermining of my own faith in places like the FDA, not to mention movies like Dope Sick.
01:11:08.020But there are all sorts of reasons to be skeptical of them and whether they're acting in our best interest.
01:11:13.340Let's not even get started on covid and the vaccine and so on.
01:11:17.540I just think people see this sort of this rubber stamping of drugs that really might be hurting the sickest and most suffering amongst us.
01:11:57.640And you really can't put the toothpaste back in the tube.
01:12:01.180Once you've given out millions and millions of dollars of grants for what is now a suspect result, are you going to ask for that the grants be returned?
01:12:12.860In this case, again, this is there's some important nuances here.
01:12:17.060It may turn out, just as Professor Ash has suggested to you, it sounds like today, that this will all turn out to be supportive of her theory and supportive of the work they originally published, even though there are clear red flags about how this was presented.
01:12:34.040Or it may turn out, or it may turn out not to be the case.
01:12:37.000And so you're right, this is really concerning.
01:12:40.300And I think it just shows how complicated and how difficult research into human conditions is.
01:12:47.960And the fact that humans are complicated organisms.
01:12:51.680And there's a lot going on here, far more than just amyloid.
01:12:56.680Multiple amyloid species clearly have toxic effects.
01:13:00.800But the question is, is that the cause of Alzheimer's?
01:13:04.400It is likely to be a mediator, but not the upstream cause of what's going wrong in an Alzheimer's brain.
01:14:23.500You can support them and so forth and so on.
01:14:25.980And in fact, the big issue with Alzheimer's, as you know, is the loss of those synapses.
01:14:30.440So what our research suggested, and we've just published a successful clinical trial based on the implications of this, is that you have this is a network.
01:14:39.780This is just like running a large company or running a country.
01:14:43.880There are many, many different contributors.
01:14:46.780And in the case of Alzheimer's, we initially identified 36 different contributors.
01:14:58.100And so insulin resistance is critical.
01:15:01.200Ongoing inflammation, various pathogens, various toxins.
01:15:05.920All of these things can change that network function.
01:15:10.980And so the idea of just doing the same thing for each person, it's like taking every single car that comes into a garage not doing well and just filling it up with gas.
01:15:21.820Yeah, a couple of the cars, that's going to be fine.
01:15:24.160But you need ultimately to treat these cars as complex mechanics and look at what's going on.
01:15:33.480And the same thing needs to be done for people with Alzheimer's, and it is not being done in mainstream medicine.
01:15:39.600We need to look at many, many different contributors.
01:15:43.360We need to have computer-based algorithms that will now look at these data and say, okay, in this particular person, it was mainly A, B, C, D, E.
01:15:52.120In this person, it was mainly F, G, H, I, J, et cetera.
01:15:55.420Well, let me ask you a question about that, because I'm just looking at the specific factors got my brain moving.
01:15:59.900So you could have a person who came in to see you who says, very outgoing, extroverted person who says, I've got tons of friends.
01:16:08.760I love to smoke and drink with them many nights a week.
01:18:13.920And we need to have more doctors understand this very point that you need to know if someone has a leaky gut.
01:18:20.640You need to know, by the way, not only about their gut microbiome, as you mentioned, but also about their oral and nasal and sinus microbiome.
01:19:06.960So there are many different pieces we have to look at here.
01:19:10.540And I think this is where medicine is headed.
01:19:13.480What, is there a society on Earth where they really don't get Alzheimer's or dementia?
01:19:19.460There are societies where there is less.
01:19:22.980But there, other than people dying young, it is all over the world.
01:19:27.660But yes, for example, it's been argued that people who, you know, who eat curcumin, for example, people in India, as you can imagine, part of the problem here is curcumin, yeah, turmeric, which happens to have a nice anti-inflammatory property.
01:19:43.600And this has been eaten for, you know, thousands of years.
01:19:47.240And yes, there seems to be a little bit less in that particular group.
01:19:51.880And of course, there are others, some areas, for example, Okinawa, where people live long lives and have, in general, longer health spans.
01:20:01.320Of course, Dan Buechner's Blue Zones, so-called.
01:20:05.720But the answer is no, there's no place where people simply don't get it.
01:21:43.320But plant-rich for all the phytonutrients should be high fiber and should be colorful and should be associated with a period of fasting that allows you to be metabolically flexible.
01:21:57.000And that means able to burn glucose, able to burn ketones.
01:22:00.620Most people, as I mentioned, who have Alzheimer's or pre-Alzheimer's are unable to burn either of those.
01:22:08.480Last time we were on, you mentioned coffee.
01:22:10.820My husband gave it up for, I don't know why, but he started to resume because of the brief conversation we had.
01:22:18.720Absolutely, and some beautiful work out of University of Florida has shown that, in fact, coffee, it reduces your likelihood of developing Alzheimer's.
01:22:31.740You know, it can be stressful for your adrenals.
01:22:33.820It can interfere with your sleep, of course.
01:22:36.360But it does, in terms of just epidemiology, it is associated with a lower likelihood of developing Alzheimer's disease.
01:22:44.100Women get it more often than men, at least in America.
01:22:49.600And I was sitting there getting my hair done before the show today, and I was thinking, I was breathing in all the toxins from the hairspray and the other products that she uses.
01:23:02.460And I was like, we should do a study to see whether news anchors or actresses or people who have to get their hair done or women who work in hair salons get it more often than women just who have naturally gorgeous hair and don't need all that nonsense.
01:23:14.460I'm telling you, it's like the toxins.
01:23:15.820That's what I'm going for, the toxins.
01:23:33.980And part of the reason may be because of the rapid hormonal change during menopause, where you lose estradiol rapidly, because estradiol does have a beautiful anti-Alzheimer effect.
01:23:45.840And as you indicated, exposure to toxins, we've been very surprised at how commonly toxins are one of the important contributors to cognitive decline that turns out to be associated with Alzheimer's disease.
01:27:13.780You're saying that memory has not been your strong suit since you were younger.
01:27:17.300And so that's a very important point, because what we're looking for, which is, again, why everyone should have a baseline if they're 45 or over, is that we want to know change.
01:27:28.980And so we've had an example for one example where a guy who was the math champion of his entire state began to have very significant dementia.
01:27:39.280And his wife took him in to see a neuropsychologist who said, oh, great news, you're scoring in the 50th percentile, so you have no problems.