Editing 19: Bret Weinstein - The Prediction and the DISC/lang-it
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'''Bret:''' | '''Bret:''' Yeah, I think, I think that's well said. So anyway, I left the room feeling like I had just glimpsed something so important, kind of, you know, I wondered could it be right and I started to just do the first bit of library research to figure out whether somebody else knew what I knew orâ | ||
'''Eric:''' | '''Eric:''' So I'm not even sure that you fully said it. I want to make sure that I'm even clear on it and I'm going to, I think I'm right, but correct me if I'm wrong. What you're saying is, âWhat if the Hayflick limit is a protection against dying from immortality at a cytological levelâ, that some cell gets a dream of immortality that it shouldn't have because, let's say, it's a somatic cell, and it says, âOkay, I just want to keep dividing and dividing and dividingâ. Nature knows how to do this, and that immortality, which sounds good at first, is actually called cancer. And so in computer science we would say, okay, you've introduced a recursion limit into a while loop or a for loop to make sure that you don't have a resource leak, which is what a tumor is. | ||
'''Bret:''' | '''Bret:''' Yeah, so let me say it this way. If you have a damage to a tissue cut on your arm or something, the cells on both sides of that cut suddenly become aware that there is a problem, a gap, because the can't hear a neighbor on one side of them and their natural reaction is to start growing into the gap until they can hear a neighbor which is the sign to stop. If you imagine that something like that is occurring in every tissue, or almost every tissue, the problem is that that means that every tissue in your body for which that story is about right, is in danger of having damage from radiation or whatever, turn it deaf to its neighbors. A single cell that has turned deaf to its neighbors will suddenly start replicating, and if it is deaf to its neighbors, then there's no message that it's going to hear that's going to tell it to stop. So that thing, imagine any cell in your body just taking off and growing and growing and growingâ | ||
'''Eric:''' Okay, | '''Eric:''' Okay, this is terrifying. What you're saying to me is, is that if I'm comprise of let's say 30 trillion cells and I view them as each let's say subroutines, any subroutine that is not denucleated, right? Like this wouldn't happen in the in the lens of your eye because the nucleus has been removed, but any other reasonable cell is potentially your assassin, because it's mitosis process might completely go rogue. | ||
'''Bret:''' | '''Bret:''' It can run away. Â | ||
'''Eric:''' Okay. | '''Eric:''' Okay. Â | ||
'''Bret:''' | '''Bret:''' And so the rather elegant and very simple idea is that there would be a hard limit so that any cell that had become damaged, so it started down this path would just simply run into the number of cell divisions it was allowed in a lifetime and it would stop. Â | ||
'''Eric:''' | '''Eric:''' So like, the moles on my face that some of my less couth commenters loved to talk aboutâ | ||
'''Bret:''' | '''Bret:''' Yep. | ||
(01:08:01) | (01:08:01) | ||
'''Eric:''' | '''Eric:''' Are effectively attempts to kill me that may have stopped. And that the perimeter where they stop is where the Hayflick limit took over and said, âThis cell line must die so that the patient will liveâ? | ||
''' | '''Bret:''' Yeah. The name I gave him was âprototumorâ and the idea is a prototumor is a patch of cells arrested at their Hayflick limit. Because they had become unregulated. If you go to the dermatologist and you say, what do I look for? You know, they tell you certain things to look for. So a round patch of cells that suddenly becomes irregular in shape. Well that's what would happen if you took one of those cells and gave it a second mutation and it started growing again. Â | ||
''' | '''Eric:''' Got it. Â | ||
''' | '''Bret:''' Right. So anyway, the idea that a limit on cellular reproductionâ | ||
''' | '''Eric:''' Yep. | ||
''' | '''Bret:''' Is adaptive to protect you from cancerâ | ||
'''Bret:''' | '''Eric:''' K, so there's a little bit of a mind bender because what you're telling me is that I've got to avoid immortality, which can kill me, and that the solution to not dying is death. | ||
 | |||
'''Bret:''' Yes, and that what selection does is it balances these two competing forces to give you as much vigor and longevity as it can. | |||
(01:09:00) | (01:09:00) | ||
'''Eric:''' | '''Eric:''' So all of the other diseases and insults and things that I can die from sort of start to fade away. And at the complete core of biology, in this theory, there are two things that I can't get away from, one of which is death by immortality, and the other one is death by recursion limit. Â | ||
'''Bret:''' | '''Bret:''' That's it. Â | ||
'''Eric:''' | '''Eric:''' It's a very elegant thing. And now the problem is, is that there's all this weird attended complexity that you had to deal with. Â | ||
'''Bret:''' | '''Bret:''' Right | ||
'''Eric:''' | '''Eric:''' So it was like stem cells versus germ versus ... | ||
'''Bret:''' | '''Bret:''' So when I went into the literature, what I found was that people had played around in the neighborhood, but that there was a particular fact which blocked every attempt to make sense of what was going on. And the fact was that rodents were understood to have ultra long, hypervariable telomeres. And I didn't know what that meant at first, but the more I looked into this possibility, the more I realized that dozens of longstanding problems would be solved if my hypothesis was true, but that my hypothesis couldn't be true because basically mice have long telomeres in short lives. Why is that? And I banged my head on the table for a couple of weeks trying to figure out what was going on. Â | ||
'''Eric:''' | '''Eric:''' Figuratively | ||
'''Bret:''' | '''Bret:''' Yes, maybe even literally on occasion. But the question was, I began to wonder if there was something wrong with the idea that mice had long telomeres. Sometimes, like in Hayflick's case it turned out that a bunch of people were copying some wrong result, so it seemed like a lot of people had seen it, but only one had. And I checked, was it true, that there was some, that everybody was parroting one study that said mice had long telomeres? Â | ||
'''Eric:''' | '''Eric:''' Right. | ||
'''Bret:''' | '''Bret:''' It turns out lots of people had tested it. Mice have long telomeres like 10 times the length of human telomeres. It just didn't fit. So finally, it occurred to me that it was possible that what was going onâI discovered something in trying to figure out what they meant by âmiceâ. Right? There's a lot of species of mice, but all the mice that we use in the lab, with rare exception, are from one genus, and often from a particular target species. Â | ||
'''Eric:''' | '''Eric:''' So you were focused, if I recall correctly, on mus spretus  | ||
'''Bret:''' Mus musculus, | '''Bret:''' Mus musculus, which is the common one. What shocked me was that it turned out all the mus musculus that were being used in labs across the country, and in many cases, farther afield than that were coming from one place, which I had no idea. There was oneâ | ||
'''Eric:''' | '''Eric:''' I remember getting a phone call when you said, what do you know about the [https://en.wikipedia.org/wiki/Jackson_Laboratory JAX Lab]? | ||
'''Bret:''' | '''Bret:''' The [https://en.wikipedia.org/wiki/Jackson_Laboratory JAX Lab] in Bar Harbor Maine, right? They seemed to be the source of everybody's mice. And so it began to beâit was a possibility I could not shut down in my mind, that there was something about what was going on at the JAX Lab that had resulted in the mice that were being sent out to all these other labsâ | ||
'''Eric:''' | '''Eric:''' Is it that they were representative animalsâ | ||
(01:12:04) | (01:12:04) | ||
'''Bret:''' | '''Bret:''' Right, these are a model organism. People were just using mice because mice were a convenient mammal, but they're all coming from one place, and it began to occur to me that that one place was not just a source of mice in the sense that we might think it, it was actually a selective environment that was impacting those mice. And when I dug deeper, it turned out that the mice had all, they were descendants of a long lineage that had lived in captivity under conditions at the [https://en.wikipedia.org/wiki/Jackson_Laboratory JAX Lab]. And at some point I realized that the most likely thing going on was that there was something about this environment that had wildly elongated the telomeres of these mice. And that was simultaneously an unbelievable idea, but the only one I could think of that made sense of everything I had seen. And soâ | ||
'''Eric:''' | '''Eric:''' Well, it's unbelievable because the consequences, I mean, look, I have not even heard whether anyone has said, âYeah, we did that, we screwed that up.â But it is, like, your favorite model organism for mammalian trials being screwed up by a central facility. Because also there's this weird thing where medical people very often stop taking into account evolutionary theory because they treat that as âWell, that's that class I took in college or the beginning of graduate school.â | ||
'''Bret:''' | '''Bret:''' Right. So I began to focus on this question and I did something that was the right thing to do, but I did it in a way I will forever regret. I found somebody who was represented in the literature, who I regarded as very well versed. They made sense to me, their papers. Her name was [https://en.wikipedia.org/wiki/Carol_W._Greider Carol Greider]. Carol Greider is now a Nobel Laureate. She was not at the time. She was the co-discoverer of the enzyme [https://en.wikipedia.org/wiki/Telomerase telomerase], which is the enzyme that elongates telomeres, when that occursâ | ||
( | (01:14:01) | ||
'''Eric:''' | '''Eric:''' With the famous and co-Nobel recipientâshe was the student of [https://en.wikipedia.org/wiki/Elizabeth_Blackburn Elizabeth Blackburn]. | ||
'''Bret:''' Elizabeth Blackburn. | '''Bret:''' [https://en.wikipedia.org/wiki/Elizabeth_Blackburn Elizabeth Blackburn]. Exactly. She was her student and they shared the Nobel prize with [https://en.wikipedia.org/wiki/Jack_W._Szostak Szostak]. In any case, her work seemed good to me. I called her up, cold, you know, I went into the insect division office and I sat down at the phone. I called her, I said, Carol, you don't know me. I'm a graduate student at Michigan. I'm an evolutionary biologist. I'm racking my brains trying to understand something. Can you tell me, is it possible that mice don't have ultra long telomeres? That it's only laboratory mice that do? And she said, huh, that's really interesting. I'm pretty sure that mice have long telomeres universally. But it is odd that if you order mus spretus instead of mus musculus and you order from European suppliers, the lengths are very different than what you get if you order mus musculus from the JAX Lab. I said, Whoa. | ||
And she said, yeah, that's really interesting. And then she said, I can't remember if it was the same phone call or if we had a second phone call, but she said she was gonna put her student, her graduate student, [https://biology.mit.edu/profile/michael-t-hemann/ Mike Hemann], who I think is now at MIT, on the project. And he was going to do a little work to figure out whether there was anything to this. And Mike did some work. They sourced some different strains of mice that were, they were actually not wild mice. Wild mice would have been the right test, but she couldn't get wild mice for obvious reasons. Â | |||
'''Eric:''' | '''Eric:''' Youâd have to go out into the woods. | ||
'''Bret:''' | '''Bret:''' Right, exactly. And so she got several different strains of mice that had just been in captivity much less time. She actually got one strain of mice that was treated very differently in captivity. But nevermind. She put her graduate student on it, and he measured their telomere lengths. And I get this excited email. [https://biology.mit.edu/profile/michael-t-hemann/ Mike Hemann] sends me any email that says effectively, âWhoa! The hypothesis is true, mice have short telomeres!â Right? Nowâ | ||
'''Eric:''' | '''Eric:''' I'm sorry, this is like as close to a who'd done it Discovery J'accuseâ the mice, you know, I remember, you were over the moon. Â | ||
'''Bret:''' | '''Bret:''' I still am! I still can look at this email and it is the moment at which I realized, A, there's no way I'm kidding myself about how well I understand this. | ||
'''Eric:''' | '''Eric:''' Right. | ||
'''Bret:''' | '''Bret:''' Right? That prediction wasâ | ||
'''Eric:''' | '''Eric:''' How old are you? Â | ||
'''Bret:''' | '''Bret:''' Now? Or then? | ||
'''Eric:''' No, | '''Eric:''' No, when you get this email. | ||
'''Bret:''' | '''Bret:''' When I got that email it was 1999? 98? Something like that. Â | ||
'''Eric:''' Okay | '''Eric:''' Okay. So over 20 years ago. Â | ||
'''Bret:''' | '''Bret:''' Yeah. So I get this email, andâ | ||
'''Eric:''' | '''Eric:''' By the way, that puts you at about 30. You're at the beginning of your career, and youâin this story, you've just predicted thatâ | ||
'''Bret:''' | '''Bret:''' It's a stunning coup for a graduate student. And, it wasn't in my advisorâs wheelhouse, so it was clearly my own work. And, I mean, Dick was great about not blurring those things, butâ | ||
'''Eric:''' Okay, | '''Eric:''' Okay, either you are a dirty dog liarâ | ||
'''Bret:''' | '''Bret:''' Right | ||
(01:17:10) | (01:17:10) | ||
'''Eric:''' | '''Eric:''' And I was there at the timeâ | ||
'''Bret:''' | '''Bret:''' Yeah. Â | ||
'''Eric:''' | '''Eric:''' Or, so we're both dirty dog liars about this particular storyâ | ||
'''Bret:''' | '''Bret:''' Orâ | ||
'''Eric:''' | '''Eric:''' Or, one of the great moments in evolutionary theory, which isâand let me just curate this, because I'm not a biologist, but I think I can more or less get thisâbecause it's a breeding protocol that is the alteration in the evolutionary landscape for these laboratory mice, and because it's acting on a non-protein coding region, the adaptation to a change in the breeding protocol can be extremely rapid. It doesn't have to undergo some sort of completely crazy typical Darwinian story about random mutation and some of them being retained and others being rejected. Â | ||
'''Bret:''' | '''Bret:''' It's even better than that. The creatures are presumablyâso we haven't gotten to what the breeding protocol has to do with thisâbut the creatures are built in some sense to detect how dangerous their environment is, and to the extent that the level of extrinsic danger changes, their telomeres respond quickly so that they are better adapted to the environment. So, they're built to detect the environment and then what is actually a strict matter of market forces. Â | ||
'''Eric:''' Okay, | '''Eric:''' Okay, so there are no predators in this environment. | ||
'''Bret:''' | '''Bret:''' No predators in this environment. | ||
'''Eric:''' | '''Eric:''' And we're not killing them particularly early based on their skills. So environmental insult is sort of absent. Â | ||
'''Bret:''' | '''Bret:''' Environmental insult is more or less absent. What we are doing is imposing an economic rule on breeding so that we can maximize the rate at which we turn mouse chow into mice, which is obviously economically the right thing to do, if you're selling mice to all these labs, you want to produce as many mice as cheaply as possible. So producing as many mice as peopleâ | ||
'''Eric:''' | '''Eric:''' The genius of the market! | ||
 | |||
'''Bret:''' | '''Bret:''' It's the genius of the market. | ||
(01:19:08) | (01:19:08) | ||
'''Eric:''' | '''Eric:''' There you go. Â | ||
'''Bret:''' | '''Bret:''' So in order to produce as many mice as cheaply as possible, what you do is you don't breed animals past eight months. They breed faster when they're younger because of senescence. And so you don't breed older mice. You throw them out and you replace them with younger mice who breed faster. What that effectively did was it eliminated the selection against cancer, and it turbocharged the selection in favor of youthful vigor | ||
'''Eric:''' | '''Eric:''' Well let me see if I get thisâin general, almost all cancers, like, cancer of the germline happens early in life, but all the other cancer, in general, is much more common later in life. Â | ||
'''Bret:''' | '''Bret:''' I gotta pause. I realize I forgot to tell you one thing Carol told me in my first phone call with her thatâs vital. | ||
'''Eric:''' | '''Eric:''' Sure. | ||
'''Bret:''' In | '''Bret:''' In addition to telling me that there was something funny about mus spretus, she told me that, consistent with the hypothesis that I was conveying to her, that all mice die of cancer. She said, âIf you let them live long enough, and then you do the necropsy, you find cancer of one kind or anotherâ, and that was perfectly consistent because they had these wildly long telomeres and no cancer protection. That would be the prediction of the hypothesisâ | ||
'''Eric:''' | '''Eric:''' Thatâs an extrapolationâit's not really all mice. It's all mice that we see in the lab, which happens to be the mice that are ordered. Â | ||
'''Bret:''' | '''Bret:''' Right. She was still speaking from the mindset of somebody who thought that the mice she was getting in the mail representative representative of mice in the wild. Â | ||
'''Eric:''' | '''Eric:''' Got it. Â | ||
'''Bret:''' | '''Bret:''' Okay, so let me clear up why the breeding protocolâand I should say, that it is the breeding protocol that is causing this? That part, I would say, is still a hypothesis. It has not been directly tested by anybody, but, what I would say is that many hypotheses were tested in the aftermath of the discovery, that lab mice have bizarrely long telomeres, and wild mice donât, and no other hypothesis has stood up to scrutiny. So it is the last hypothesis standing and I'm all but certain that it will turn out to be true. Â | ||
'''Eric:''' | '''Eric:''' Yeah. Â | ||
'''Bret:''' | '''Bret:''' The reason that the breeding protocol has this weird effect, is that when you throw out the mice at eight months of age, you eliminate selection against cancer, you turbocharge selection in favor ofâ | ||
'''Eric:''' | '''Eric:''' Sorry, when you throw out the mice, for breeding purposes, at eight months of age. | ||
'''Bret:''' | '''Bret:''' Right, | ||
'''Eric:''' Okay. | '''Eric:''' Okay. Â | ||
'''Bret:''' | '''Bret:''' When you throw them out for breeding purposes at eight months of age, you are increasing the importance of their early life breeding, and you are discounting anything related to their ability to fend off cancer because they don't live long enough in that period of time to get cancers that kill them. And so what has happened, according to this hypothesis, is that the mice that have longer telomeres have driven out the other animals from the colony. The trait of having long telomeres has swept through the colony and the telomeres have been elongated to an absurd degree, creating animals that do all die of cancer. And interestingly enough, another thing that's evident from the literature is that if you look at their tissues, their tissues do not age in the way that a normal mammalâs tissues age, they remain young. Â | ||
'''Eric:''' | '''Eric:''' So there's one aspect of aging, but that there's a far darker interpretation of what you've just said. If I'm understanding youâcorrect me, Iâve never taken a class in biology, but I lived this adventure with youâthose tissues have, at a histological level, the level of how cells are organized, the possibility of radical histological repair. Â | ||
'''Bret:''' | '''Bret:''' Yes, radical effectively indefinite capacity to repair, which is going to come back in this story in the worst possible way. Soâ | ||
'''Eric:''' | '''Eric:''' This is like aâI mean, I just forget how great of aâ | ||
'''Bret:''' | '''Bret:''' Me too, I go years sometimes without thinking deeply about it. | ||
'''Eric:''' | '''Eric:''' Without telling the story. Alright. | ||
(01:23:06) | (01:23:06) | ||
'''Bret:''' | '''Bret:''' Yeah. Okay. So the story now gets kind of ugly. I recognize I've got all the pieces of the puzzle necessary to tell the story correctly. I have taken on a coauthor, we've found the literature necessary to do it in proper scientific form. Â | ||
'''Eric:''' | '''Eric:''' This came from you, but I want to mention your coauthorâs name. Â | ||
'''Bret:''' | '''Bret:''' Yeah. Debbie Ciszek. Â | ||
'''Eric:''' Okay. | '''Eric:''' Okay. Â | ||
'''Bret:''' | '''Bret:''' And Debbie was an excellent coauthor, strong contributor to the paper. Anyway, we put together over the course of a year, I took a break from, effectively, my real dissertation work, and wrote a paper. Dick thought it was a fantastic paper. He was blown away by itâ | ||
'''Eric:''' | '''Eric:''' Well I remember the revisions, and I remember this was like, I mean, if I think about what's on the line, like this combines one of these freak situations where you're using evolutionary theory to predict something, and in this case it's at the level of molecular biology, so with Darwin's orchid it's a tongue, and with Dick's thing, its behavior in naked mole rats. This thing is actually at a molecular level, and, it couldn't be more important if mice are going to be the major system in which we are going to test drugs, which are highly sensitive to what? Histological repair. | ||
'''Bret:''' Yup. | '''Bret:''' Yup. It's so profound on several different levels that I'm super energized about getting this into the world. It's transformative. Dick looks at the paper, he says, âThis is fantasticâ. He puts me through the ringer to get it really tight. We get it tight. We send it to George Williams, theâ | ||
'''Eric:''' | '''Eric:''' The number one guy in the world. | ||
'''Bret:''' | '''Bret:''' The number one senescence guy at the evolutionary level in the world, and he writes a beautiful recommendation letter for this piece. We're going to send it to Nature. George Williams tells Nature, you need to take this piece very seriously. We send it to Nature and they send it back with one of their absurd form letters that says that âThe nature of the article is such that it's probably notâ | ||
'''Eric:''' | '''Eric:''' Of limited interestâ | ||
'''Bret:''' | '''Bret:''' To their readers. And we're, you know, I mean, we had a good laugh about that. You know, it's cancer, it's senescenceâ | ||
(01:25:10) | (01:25:10) | ||
'''Eric:''' | '''Eric:''' Dude, it's so bad. Like, this is a response that indicates either malfeasance, or an Eliza program, or the janitor ended up responding who didn't know any bioâ | ||
'''Bret:''' | '''Bret:''' Itâs the craziest thing, and you know, the cherry on top is that they're turning down George Williams recommendation? Like, how craâ do they know who he is? Like, what? Where? | ||
'''Eric:''' | '''Eric:''' On what planet? Â | ||
'''Bret:''' | '''Bret:''' On what planet do you turn down his recommendation to look at something about senescence? So, anyway, I get back this rejection, and I have purposefully not shown Carol Greider the paper in preparation, which I am afraid she might've read some way. The reason I didn't show it to her was because I wanted to preserve her independence as a reviewer for the paper. I was hoping, because I still thought she was an ally of mine, I was hoping that Nature would send it to her to review, and that she would look favorably on it, especially since it was, you know, very clear that she had doneâ | ||
'''Eric:''' | '''Eric:''' It was her lab that made the confirmation. Â | ||
'''Bret:''' | '''Bret:''' Yeah. And I, oh, another thing I forgot, I asked her at some point, something that now rings in my earsâI asked her, Carol, you've now got this result about, no, actually lab mice have long telomeres, but wild mice have short telomeres. That's a big result. Â | ||
'''Eric:''' | '''Eric:''' Thatâs a hell of a delta. Â | ||
'''Bret:''' | '''Bret:''' Where are you going to publish it so that I can cite itâ | ||
'''Eric:''' | '''Eric:''' Right. Â | ||
'''Bret:''' | '''Bret:'''In my paper, which is the natural thing to do. And she says, âwe're not going to publish it. We're going to keep the information âin house.â That was her phrase. I was too young to understand what the hell she was talking about. | ||
'''Eric:''' | '''Eric:''' I'll be honest, I'm 54 and I don't quite understand it myself. Â | ||
'''Bret:''' | '''Bret:''' Well, it's so heartbreaking. What she has effectively done is decided, âI could publish this resultâ | ||
'''Eric:''' | '''Eric:''' And then everyone would have it. | ||
'''Bret:''' | '''Bret:''' It would be huge, but then I'm on a level playing field with everybody else. If I don't publish this resultâ | ||
(01:27:16) | (01:27:16) | ||
'''Eric:''' | '''Eric:''' I have a stream of papers I can get at. | ||
'''Bret:''' | '''Bret:''' Then I can start predicting other results. Nobody will know how I am doing that thing. I will look like a super genius. And so, holding it âin houseâ is a mechanism for a whole slew of papers. | ||
'''Eric:''' | '''Eric:''' to be, to be 100. You can afford to bend over backwards and not make inferences. Let's say the following, holding it in house is any seemingly inexplicable decision in science, but for the fact that it fits at least one story of this kind, which is that it is consistent with wishing to publish a stream, rather than the source of the information that would allow youâso you can either do one discovery or you can do a stream of predictions and that makes a certain amount of sense, given the ruthlessly competitive grant-winning environment. And we don't know exactly what happened, but there is no world that I know of in which you're allowed to hold back that kind of information, because, in part, of what's on the line. Â | ||
'''Bret:''' | '''Bret:''' Right. Soâ | ||
'''Eric:''' | '''Eric:''' I mean, this is not just a question of academic interestâ | ||
'''Bret:''' No. | '''Bret:''' No. | ||
'''Eric:''' | '''Eric:''' Because these mice are used for medical testing. Â | ||
'''Bret:''' | '''Bret:''' Not even that. It's medical testing, but it's also all of the science relative, at least, to cancer, senescence, wound healingâall of the science that is stacked on these mice that is contingent on their function relative to their tiers is all compromised. You're letting year after year of this stuff accumulate. It's malpractice at an incredible level. So, I don't know that she has turned on me, but I call her up, and I say, âCarol, we are stunned to find that our paper was turned away without review from Natureââ | ||
'''Eric:''' | '''Eric:''' Without review. | ||
'''Bret:''' | '''Bret:''' Without review. We need your help. Can I send you the paper and have you look at it? And she says yes. And I sent her the paper and she sends back the paper with an unbelievable number of intense criticisms that are not sensible. She pans the paper, does not believe itâ | ||
'''Eric:''' | '''Eric:''' Do you still have that copy? | ||
'''Bret:''' | '''Bret:''' I have that paper, I have that paper with her handwriting. I believe I also have the FedEx envelope in which she sent it to me. But she hates the paper, and I have now forgotten a bit of the sequence. But as I am attempting to fix this up for another journalâoh, here's a, sorry, I hate to tangle this story, but it's important to get it right. | ||
'''Eric:''' No | '''Eric:''' No but you havenât told this in enoughâ | ||
'''Bret:''' | '''Bret:''' I haven't told it in a very long time. After the rejection from nature, after Carol has seen the paper, and said it's cruddy, I get a letter I don't expect from a journal I don'tâI know it exists, but I'm not super familiar with it, Experimental Gerontology. Experimental Gerontology says, âWe are the editors of experimental gerontology. We have heard a rumor of your work. We're very interested. Would you be willing to submit a version to our journal?â and, oh, this is happening prior to Carol looking at my paper and panning it. Â | ||
'''Eric:''' | '''Eric:''' So the only way they would have known about this would have been from Nature or from Dick, orâ | ||
'''Bret:''' | '''Bret:''' I'm pretty sure I know, based on what they, again, I was too young to sort out really what they were saying, but they indicate that they're fans of antagonistic pleiotropy, so what happened was George Williams, having heard that it got rejected, contacted some friends of his and was like, you should really take a look at this. So I begin the process of revising it. I've shown it to Carol, she's panned it. I send the revised version to experimental gerontology. They send it out for review. As you know, review is blind. You don't know who your reviewers are, but you can often tell who they are. It's not as obscureâ | ||
'''Eric:''' | '''Eric:''' If itâs a small field. | ||
(01:32:00) | (01:32:00) | ||
'''Bret:''' | '''Bret:''' Yeah. So they read the acknowledgements of my paper, which are now on alert about Carol. I have to thank her in the paper for the work she did, but I'm now on alert that she's gone strange on the subject matter of this paper, and so I've broken her out separately in the acknowledgements. I don't want to be as gracious to her, because she's being hostile to me. | ||
'''Eric:''' | '''Eric:''' Right. Â | ||
'''Bret:''' | '''Bret:''' But I don't want to not acknowledge her, so I acknowledge her separately. Experimental Gerontology thenâI am 99% sureâsends the paper to her as the reviewer. She pans it. Absolutely brutal critiques, just pages and pages and pages of them. They are not high quality critiques. I could go through every single one. Â | ||
'''Eric:''' | '''Eric:''' Donât bother, this is a podcast, justâ | ||
'''Bret:''' No, | '''Bret:''' No, I can't do it here, but I could have thenâ | ||
'''Eric:''' No, okay? | '''Eric:''' No, okay? | ||
'''Bret:''' | '''Bret:''' But I didn't know what to do because she was in line for a Nobel Prize, that was well understood. I didn't want to accuse a leading light of the field of, | ||
'''Eric:''' Okay, | '''Eric:''' Okay, this is exactly why I got angry with the beginning of the podcast, you moron. No, no offense. You were in line for a Nobel Prize. You didn't. I mean, I'm sorry. There is an aspect of this about giving away your power, before youâve even accumulatedâyou don't even have a PhD at this time. | ||
'''Bret:''' | '''Bret:''' I'm just saying, at the time, if you mentioned her name, people would say, âOh yeah, her Nobel Prize is one of these years.â Right? So my point was, I was in the awkward positionâI didn't understand what I was supposed to do. I didn't want to send back a review that said, âI don't know who the person is who reviewed this, but they don't understand the material, and all of their critiques suckâ, because I didn't want to accuse somebody who was that powerful of not getting it. | ||
'''Eric:''' | '''Eric:''' I mean, here's the problem. What do you do? You don't actually have evidence in the hard form where like you have got videotape, but on the other hand, these are small worlds. This, all of this is preposterous. | ||
'''Bret:''' | '''Bret:''' Right. So I sit on the review for too long, not knowing what toâ | ||
'''Eric:''' | '''Eric:''' Well you don't know how to play the game! | ||
'''Bret:''' | '''Bret:''' I don't know how to handle it. Â | ||
'''Eric:''' | '''Eric:''' I'm sorry, but, like, I had no advisor. Your advisor was not equipped for the modern era. Â | ||
'''Bret:''' | '''Bret:''' He wasn't equipped for the modern era. He wasn't equipped for molecular biology. Â | ||
'''Eric:''' | '''Eric:''' That's true. Â | ||
'''Bret:''' | '''Bret:''' I finally settle on a strategy that I can live with and I send back a note. I send back the review and my note says, âI don't know why, but this entire list of critiques is not high quality. If you would like to point me to any of the critiques in this list that you would like me to address, I am more than happy to do it, but I don't think it makes sense to address the entire listâ, and as I recall it, I hit send on the email, and within minutes, maybe it was an hour, I got back a response: âYour paper has been accepted for publicationâ, which blew me away because Iâ | ||
'''Eric:''' | '''Eric:''' It makes no sense according to regular protocols. Â | ||
'''Bret:''' | '''Bret:''' Right. It makes no sense, because, clearly, they're supposed to send it out for review. The reviewer is supposed to say whether it's supposed to get published. The reviewer said it shouldn't be published. I said, âI refuse to address these critiques unless you ask me to.â The editors have overridden the reviewer. They understood the reviews were cruddy. They needed me to say that in order to justify the move that they wanted to make. They knew the paper was good and the review was crap. So they effectively overrode normal peer review. Was my paper peer reviewed? Well, it was by the editors who were experts. | ||
(01:35:28) | (01:35:28) | ||
'''Eric:''' | '''Eric:''' Let me jump in. Peer review is a cancer from outer space. It came from the biomedical community, it invaded science. The old system, becauseâI have to say this because many people who are now professional scientists have an idea that peer review has always been in our literature and it absolutely motherfucking has not. Â | ||
'''Bret:''' | '''Bret:''' Right. | ||
'''Eric:''' Okay? | '''Eric:''' Okay? It used to be that the editor of a journal took responsibility for the quality of the journal, which is why we had things like Nature crop up in the first place, because they had courageous, knowledgeable, forward thinking editors. And so I just want to be very clear, because there's a mind virus out there that says âpeer review is the sine qua non of scientific excellence, yada, yada, yada, bullshit, bullshit, bullshitâ. And if you don't believe me, go back and learn that this is a recent invasive problem in the sciences. | ||
'''Bret:''' | '''Bret:''' Recent invasive problem that has no justification for existing in light of the fact thatâ | ||
'''Eric:''' | '''Eric:''' Well, no, not only does it have no justification for existing. When Watson and Crick did the double helix, and this is the cleanest example we have, the paper was agreed should not be sent out for review because anyone who is competent would understand immediately what its implications were. There are reasons that great work cannot be peer reviewed. Furthermore, you have entire fields that are existing now with electronic archives that are not peer reviewed. Peer review is not peer review. It sounds like peer review. It is peer injunction. It is the ability for your peers to keep the world from learning about your work. | ||
'''Bret:''' | '''Bret:''' Keep the world from learning about your workâ | ||
'''Eric:''' | '''Eric:''' Because peer review is what happensâ real peer review is what happens after you've passed the bullshit thing called peer review. Â | ||
(01:37:18) | (01:37:18) | ||
'''Bret:''' | '''Bret:''' Yes. Okay, so the paper was accepted by Experimental Gerontology. They went on to publish it. Â | ||
'''Eric:''' | '''Eric:''' This is called âLifeâs Slow Fuseâ? | ||
'''Bret:''' No, âLifeâs Slow Fuseâ | '''Bret:''' No, âLifeâs Slow Fuseâ was the title as sent to Nature, and I changed the title because I did not want to compromise the storyâI didn't want to confuse the story. | ||
'''Eric:''' | '''Eric:''' The original submission was called âLifeâs Slow Fuseâ. Â | ||
'''Bret:''' | '''Bret:''' Right. | ||
'''Eric:''' | '''Eric:''' We probably have a copy of that somewhere? | ||
'''Bret:''' Oh, | '''Bret:''' Oh, of course. Â | ||
'''Eric:''' | '''Eric:''' All right. Then the Experimental Gerontology paper, what is it called? Â | ||
'''Bret:''' | '''Bret:''' The Reserve Capacity Hypothesis, which is a much less catchy title, but, nonetheless, the paper, I'm very proud of how it's written. People read it who were not expert, could understand it. The abstract is extremely clear, and it ends with the clear point that, because we have unearthed, we have predicted, and Carol Greider has shown, that wild mice telomeres are short, and the telomeres had been elongated by captivity, that there is a clear danger that the mice we are using for drug safety testing are biased in an egregious way. And the bias would look like this: a mouse that has very long telomeres has an indefinitely large capacity to replace damaged tissue, and, it has a vulnerability to cancer that is preternaturally high. So, we may be overratingâif we use these mice, we may be overrating the danger of causing cancer, and vastly underrating the danger of toxicity. And, in fact, one of the thingsâso, the point was you give a mouse who's got an effectively infinite capacity to replace its tissues, a toxin, and either the toxin is so deadly that it dies right away, but if it doesn't die right away, it just eats up the insult. So those animals would lead us to release drugsâ | ||
'''Eric:''' | '''Eric:''' By insult, what you mean is cellular necrosis? Â | ||
'''Bret:''' | '''Bret:''' Damage. Yeah. What this would cause us to do is release drugs onto the market for human use that are highly toxic across the body. | ||
'''Eric:''' | '''Eric:''' Wait a secondâif the mouse standard was the last standardâ | ||
'''Bret:''' | '''Bret:''' Well, no, even if it's not the last standard, becauseâ | ||
'''Eric:''' | '''Eric:''' Well, itâs important to say thisâ | ||
'''Bret:''' | '''Bret:''' The problem is, I mean, you can imagine how hard it is to test on large, slowly reproducing animals. Â | ||
'''Eric:''' | '''Eric:''' Well, and the ethics of testing on humans is veryâ | ||
'''Bret:''' | '''Bret:''' Absolutely. | ||
'''Eric:''' | '''Eric:''' ârestricted, so mice is the last cheap placeâ | ||
'''Bret:''' | '''Bret:''' It's the last cheap placeâ | ||
'''Eric:''' | '''Eric:''' âto get large N data. Â | ||
'''Bret:''' | '''Bret:''' Not only large N, but it's the one place that you can make the following move. You can imagine that in many circumstances the accelerated lifespan, the accelerated life cycle of mice allows you to see long term damage as it would accrue in humans on a very short timescale. That doesn't work with monkeys. It doesn't work with human patients. It works with mice, maybe, but in the case of mice with ultra long telomeres, those insults will be invisible. Â | ||
(01:40:36) | (01:40:36) | ||
'''Eric:''' | '''Eric:''' Let's just, I want to back up because I think this is a really important part of the story. What you're saying is if you take an organism that has an expected, let's say, 40 year lifetime, it's very expensive timewise to say, âWe ran this experiment and found that there was no immediate damage that was visible, but towards the very end of their lives we saw a marked increase in morbidityâ orâ | ||
'''Bret:''' | '''Bret:''' Yeah, I mean if you took a drug and it knocked 15 years off your life on average, that might not show up in any notable way in a short term study. | ||
'''Eric:''' | '''Eric:''' If there was pressure toâ | ||
'''Bret:''' | '''Bret:''' Right. And nobody is going to want to let drugs, you know, you don't want to wait 40, 50 years to find out what happens to these patients. So what we do is we make the assumption that if we give large amounts of a drug to an animal that lives a very short life, we will see those effects early. And if the animal happens to have ultra long telomeres, you won't see those effects early. So, it's a perfect storm for causing us to release drugs that should never have been released into public. Â | ||
'''Eric:''' | '''Eric:''' Can you think of one? | ||
'''Bret:''' Oh, | '''Bret:''' Oh, I sure can. [https://en.wikipedia.org/wiki/Rofecoxib Vioxx], for example. So Vioxx was discovered to do heart damage, right? Heart damage. How do you, why do we know that it's heart damage? Well, the thing about hearts, for reasons we can get into maybe another time, hearts have a very low capacity for self-repair, right? That's why they're vulnerable to heart attack. | ||
'''Eric:''' | '''Eric:''' Not much turnover. | ||
'''Bret:''' | '''Bret:''' Not much capacity for repair, and not much turnover. Now, there's an adaptive reason for that, but hearts don't repair themselves very well in a healthy person. And when they fail, it's hard to ignore, right? If somebody who's 30 has their heart fail, there's questions asked, right? So anyway, Vioxx was released into the public having passed drug safety testing. | ||
'''Eric:''' | '''Eric:''' This isnât the only system that doesn't have a lot of mitosis, like for example, neurons. | ||
'''Bret:''' | '''Bret:''' Neurons don't have a lot, cartilage doesn't have a lot. Â | ||
'''Eric:''' | '''Eric:''' Got it. | ||
'''Bret:''' | '''Bret:''' Your eye cells don't. Now note, all of the tissues I've just mentioned, when's the last time you heard about anybody having, you know, cancer of the cartilage, of their knee, cancer of the heart, | ||
'''Eric:''' | '''Eric:''' If they get brain cancer, it tends to be glialâ | ||
'''Bret:''' | '''Bret:''' Itâs glial cells, exactly. So the tissues that have very low capacity for self repair do tend to wear out and they don't tend to get cancer, which is exactly one of the predictions of my paper. Â | ||
'''Eric:''' | '''Eric:''' Right. | ||
'''Bret:''' Okay. | '''Bret:''' Okay. So Vioxx is known to do heart damage. That created a big scandal because how the hell did it get through drug safety testing? It turns out a lot of drugs have done this. We've seen it with Gleevec, Fen Phen, Arithromycin. Your doctors probably still doesn't know that Arithromycin does heart damageâ | ||
'''Eric:''' | '''Eric:''' Yikes | ||
'''Bret:''' | '''Bret:''' Right. There's all of these cases of drugs that were released and then later understood to do heart damage. Now my claim is they don't actually do heart damage. They do cellular damage and the heart is the most conspicuous. Â | ||
'''Eric:''' | '''Eric:''' Yeah, yeah, yeah, yeah. Geez. This is like another layer of this thing. Â | ||
'''Bret:''' | '''Bret:''' It's like a huge fucking nightmare, right? Becauseâ | ||
'''Eric:''' | '''Eric:''' Well, but it's this thing about, like, perseverance and disagreeability. You've got all sorts of things that sound like something that invalidates the theory, and then itâs sort of theories upon theories that allow you to see the original simplicity of the idea. I see the original idea is very simpleâ | ||
'''Bret:''' | '''Bret:''' Yep. | ||
'''Eric:''' | '''Eric:''' âbut if you know a lot of weird facts about what you think are just mice, or something about hearts, you can't put together what is going on. The idea that ambient damages only manifest in the heart because that's the one systemâyou know, or the neural systemâthat, like, really doesn't have a lot of mitosis. | ||
(01:44:17) | (01:44:17) | ||
'''Bret:''' | '''Bret:''' So, well, piece of advice to anybody who finds themselves in remotely similar waters. The signal that you are on the right track is that stuff starts canceling. Complexity in the story, which has accumulated because something was missing, starts disappearing in the story. You begin to take on a model. Anyway, so yes, we've got a situation where we've got a bunch of drugs mysteriously producing heart damage. | ||
'''Eric:''' | '''Eric:''' K, so now you've got a paper that's out. You've got a real world application. You've got a theory coming out of evolutionary theory. It's making a molecular prediction. Â | ||
'''Bret:''' | '''Bret:''' Yup. Successfully predicts mouse telomeres. Â | ||
'''Eric:''' | '''Eric:''' One of the world's leading labs has confirmed the prediction. Â | ||
'''Bret:''' | '''Bret:''' Yup. | ||
'''Eric:''' | '''Eric:''' Where are we now? What year is this? Â | ||
'''Bret:''' | '''Bret:''' God, well, let's see. The paper came out | ||
'''Eric:''' | '''Eric:''' And my recollectionâand, just to be horrible about thisâis that your fucking department at the university of Michigan, which has some great people, is also holding you back and enervating you year after year by not allowingâbecause this is groundbreaking stuff. This is Nobel quality work, at least one or two times over, in my opinion. I could be wrong. I'm biased because I'm your brother, but what concerns me here is that you are not comfortable with what this story really might be. Â | ||
'''Bret:''' No | '''Bret:''' No Iâ Look, it's not mine to judge. I'm very proud of this work and the workâ | ||
'''Eric:''' | '''Eric:''' But the problem, Bret, is that Jerry Coyne and Richard Dawkins did not know that Dick Alexander, Leonard Hayflick, and George Williams were all on this thing, because that community had broken down. | ||
(01:45:59) | (01:45:59) | ||
'''Bret:''' | '''Bret:''' You know, the irony is, I sent a letter to Dawkins when this was going on, asking for his help, and he sent back a letter saying, âThis is very interesting. It's not my area of specialty. You should talk to [https://en.wikipedia.org/wiki/W._D._Hamilton Bill Hamilton].â And I was in the process of writing a letter to Bill Hamilton on Dawkinâs suggestion, at the point that Bill Hamilton came back from Africa havingâhe was pursuing a remote hypothesis about humans having accidentally unleashed AIDS into the world with a polio vaccine. But anyway, soâ | ||
'''Eric:''' Bill Hamilton, | '''Eric:''' Bill Hamilton, I'm sorry, not everybody's going to knowâthis is the guy who came up with inclusive fitness? Â | ||
'''Bret:''' | '''Bret:''' Yes. He was one of the great geniuses of evolutionary biology in the late 20th century. Â | ||
'''Eric:''' | '''Eric:''' He was held back by John Maynard, right? Â | ||
'''Bret:''' | '''Bret:''' I don't know that story. I, you knowâ | ||
'''Eric:''' | '''Eric:''' I think Maynard is interviewed on Web of Stories where youâ | ||
'''Bret:''' Maynard Smith. | '''Bret:''' Maynard Smith. Â | ||
'''Eric:''' | '''Eric:''' Yeah, sorry. Yeah. Maynard Smith. Right. Â | ||
'''Bret:''' | '''Bret:''' Yeah. Â | ||
'''Eric:''' | '''Eric:''' And Maynard Smith talks about like, you know, âIt was very unfortunate. I didn't really understand who he was.â You should check it out. It's pretty amazing. Â | ||
'''Bret:''' | '''Bret:''' Well, as long as we're doing this, years after this story had cooledâ | ||
'''Eric:''' | '''Eric:''' Yeah. Â | ||
'''Bret:''' | '''Bret:''' âI ran across a paper from John Maynard Smith that, I now don't remember exactly what its nature was, but it appeared to predict my whole story. Â | ||
'''Eric:''' Uh-huh | '''Eric:''' Uh-huh | ||
'''Bret:''' | '''Bret:''' Right? And John Maynard Smith was dead. I couldn't contact him. I really wanted to say, âOh my God, you nailed it.â Right. But anyway, so I was in the process of writing to Bill Hamilton to get his help. You know, he was sort of on a par with George Williams, and he went into a coma on his trip back from Africa having contracted malaria. And then there was, I think complication with the aspirin that he took or something. And he never woke from his coma and he died, tragically. So he never got the letter, and who knows what he would've done. Â | ||
'''Eric:''' Okay, | '''Eric:''' Okay, but look, that's a tragic and interesting story, but Hayflick was positive towards you. Williams was positive towards you and Dick Alexander. Those were the three that blew me away. That's a huge amount of firepower. | ||
'''Bret:''' | '''Bret:''' Thatâs a lot of firepower, and it wasn't enough. But, here's the punchline to the story, effectively. At the point that my paper is outâ | ||
'''Eric:''' | '''Eric:''' Right. Â | ||
'''Bret:''' | '''Bret:''' âand it very directly alleges the danger with these drugs being released when they're not safe, and the drugs have started emerging and turning out not to be safe, and the government is now really interested in what's going on, the government puts together a FDA commission to study the question ofâthe book that they put out, literally a book that they put out, at the end of their study is called The Future of Drug Safety | ||
'''Eric:''' | '''Eric:''' I hope itâs a Blue Ribbon panel. | ||
(01:48:53) | (01:48:53) | ||
'''Bret:''' | '''Bret:'''It's not exactly clear what it was. What is clear is that you can search the manuscript of this book. Nowhere does it mention âmouseââ | ||
 | |||
'''Eric:''' Antagonistic pleiotropy? | |||
''' | '''Bret:''' It doesn't mention antagonistic pleiotropy. It doesn't mention the genus âmusâ. It doesn't mention âtelomeresâ. It's not in there. It's alleged in the literature in broad daylight that this is what is causing the problem, andâ | ||
''' | '''Eric:''' Now you'reâsee, this is the Vampire Effect, where you don't exist if nobody reacts. Â | ||
''' | '''Bret:''' Right. And, so I start going to members of the press, I think, âThis is a huge goddamn story. Somebody is going to makeâ | ||
''' | '''Eric:''' âOh my god, youâre self promoting!â | ||
''' | '''Bret:''' âcareer on itâ, and I call up members of the press, and it's always the same, right? | ||
''' | '''Eric:''' Always the same. | ||
''' | '''Bret:''' Itâs always the same. They're very excited about this story. Â | ||
''' | '''Eric:''' No, theyâre initially, the reporterâ | ||
''' | '''Bret:''' The reporter is excited. | ||
''' | '''Eric:''' Yep | ||
''' | '''Bret:''' And then the reporterâ | ||
'''Bret:''' | '''Eric:''' Talks to someone. | ||
 | |||
'''Bret:''' They talk to someone, and then either they stop returning your calls, or they say, âI'm sorry, the story doesn't hang togetherâ. It's again and again and again. | |||
(01:49:48) | (01:49:48) | ||
'''Eric:''' | '''Eric:''' Yeah. | ||
'''Bret:''' | '''Bret:''' And there's just nothing you can do. | ||
'''Eric:''' | '''Eric:''' Remember what I said about the Distributed Idea Suppression Complex | ||
'''Bret:''' | '''Bret:''' Yeah. And the people who man it don't even know what they are. For most of them, they don't know what role they're playing. Â | ||
'''Eric:''' | '''Eric:''' Look, you see the same thing with like string theory because none of the reporters are actually string theorists, so they're dependent upon this. You saw this with this woman alleging that she had the Epstein story three years earlier, but that the editors said, well, we might lose access to the baby pictures of the Royal grandchildren like, you know, you're seeing this with catch and kill. There's this, I mean, I want you to take this seriously. You're just showing a part of what I'm calling the DISC, the Distributed Idea Suppression Complex. We have 50 years of such stories, and it happens that in our family, three out of four of us created such a story trying to get a PhD. And the idea for me is that every time you have to go into some closed system, like, there's a committee meeting or there's a blue ribbon commission or there's a peer review process, or there's a, what do they call them, the panelsâstudy groups, for grants. That's where the DISC lives. We know that it's localized to the things that protect the integrity of science. It's an autoimmune disease, where what we have is an ability to stop highly disruptive ideas from getting a hearing in the general population of experts, by virtue of the fact that a carefully chosen group of experts can stop publication. Because look, if you're wrong about this stuff, there's a cost. It's not, it's not cheap. Â | ||
'''Bret:''' No, | '''Bret:''' No, I mean, in fact, it would have been career ending. I'm pretty sure, had I beenâ | ||
'''Eric:''' | '''Eric:''' I don't know that it would be career ending if it was done in good faith, but you know, this is my, my problem with this is that you're sitting on one of the great scientific storiesâI would say that I've ever heard. But you know, I'm sort of, kind of saying, âWell, Bret, what happens next?â You know, obviously I know a lot of this stuff. I've forgotten it, but I lived this with you and this is, I can vouch that this is more or less the order of events as it was taking place, as we didn't understand what was happening. Â | ||
'''Bret:''' | '''Bret:''' So I have to go through the final Carol Greider chapter. In order for this story to fully make sense, | ||
'''Eric:''' | '''Eric:''' Where the Nobel Prize is given? Â | ||
'''Bret:''' | '''Bret:''' That's the very tail end. Â | ||
'''Eric:''' | '''Eric:''' Make sure you include that. Â | ||
(01:52:46) | (01:52:46) | ||
'''Bret:''' Okay. | '''Bret:''' Okay. So at the point that my relationship with Carol is changing its tenor and she is becoming hostile and I'm not clear on what's going on, I contact her and I discover through talking to her that she and Mike are about to publish their paper on the long telomeres of laboratory mice. Â | ||
'''Eric:''' | '''Eric:''' So this is the Delta between a wild type and laboratory mice. Â | ||
'''Bret:''' | '''Bret:''' Yeah. And I'm shocked because she's told me they're keeping it in house and instead they've got a paper that there, she says in final revisions there that day submitting their final revisions to nucleic acid research with their paper. And I say, Carol, can I see the paper? And she says yes. And she sends me a manuscript, not the pre-print of the paper. She sends me a manuscript of the paper, no acknowledgements, no figures. And I contact her and I say, can I see the acknowledgements and the figures? She sends them to me, and I contact her and I say, âCarol, I'm disturbed. This was my hypothesis that you were testing. I should probably be an author on this paper, but at the very least I need to be an acknowledgement in this paper so that I can go back and point to it and say that wasââ | ||
'''Eric:''' | '''Eric:''' It changes everything. That it was a prediction. It wasn't just something that was stumbled upon. Â | ||
'''Bret:''' | '''Bret:''' Absolutely. Â | ||
'''Eric:''' | '''Eric:''' Yeah. Â | ||
'''Bret:''' | '''Bret:''' And her response is, âI have been through my email and I see no evidence of the communications you are talking about.â Now, when I said at the beginning thatâ | ||
'''Eric:''' | '''Eric:''' You had called her. | ||
'''Bret:''' | '''Bret:''' I had called her. | ||
'''Eric:''' | '''Eric:''' Holy Shit. | ||
'''Bret:''' | '''Bret:''' That was my error. Â | ||
'''Eric:''' | '''Eric:''' This is such fucked up. I mean, I don't swear a lot in this program. Â | ||
'''Bret:''' | '''Bret:''' Yeah. Â | ||
'''Eric:''' | '''Eric:''' But this is such fucking academic, petty, stupid ass bullshit. This is like one of the great stories of all times. | ||
'''Bret:''' | '''Bret:''' One of the great stories of all time, maybe, and human life hangs in the balance on this one. Â | ||
'''Eric:''' | '''Eric:''' No kidding. | ||
'''Bret:''' | '''Bret:''' Right. Okay. So Carol does get awarded the Nobel prize, Carol Greider, Elizabeth Blackburn and Szostak. Szostak, who mentions at the point that the Nobel Prize is awarded that he was shocked as all hell to get a Nobel Prize because his work was so deep in the history of telomeres that he just didn't expect it. And suddenlyâ | ||
(01:55:14) | (01:55:14) | ||
'''Eric:''' No, | '''Eric:''' No, I should say, I want to be very clear, right. All of these people have made fantastic Nobel-worthy discoveries. Â | ||
'''Bret:''' | '''Bret:''' Totally. | ||
'''Eric:''' | '''Eric:''' There's zero allegation that these peopleâ | ||
'''Bret:''' | '''Bret:''' Weren't deserving. No, Â | ||
'''Eric:''' | '''Eric:''' Absolutely. Â | ||
'''Bret:''' No. | '''Bret:''' No. And they, you know, Carol and Elizabeth got their Nobel prize for the discovery of telomerase, which is a huge, huge progress. So anyway, I don't deny that they were worthy of this prize. What Carol Greider does with her Nobel lecture, right. Nobel lecture being the biggest lecture a scientist will ever give, the lecture thatâ | ||
'''Eric:''' | '''Eric:''' And filmed. | ||
'''Bret:''' | '''Bret:''' And filmedâis she delivers a paper in which she very oddly has now embraced my entire set of hypotheses about the effect. She has come over from the comparison between the paper of mine that she panned and said didn't make any sense. She is now a total convert to the idea that senescence across the body is being caused by Hayflick limits that are telomere based. Â | ||
'''Eric:''' Okay, | '''Eric:''' Okay, and this is the first public incident that we know of in which the delta between the negative comments on your paper, which is not an anonymous peer review. Â | ||
'''Bret:''' | '''Bret:''' We have it in an envelope from her. Â | ||
'''Eric:''' | '''Eric:''' Got it. And it's immediately after the Nobel prize that the wisdom of that line of thinking is embraced. | ||
(01:56:43) | (01:56:43) | ||
'''Bret:''' | '''Bret:''' Right. But there's more to the Nobel lecture. So she spends her Nobel lecture on what is admittedly a very beautiful presentation of the connection between telomeres and senescence. She goes through tissue after tissue, says cirrhosis of the liver is what happens when you have short telomeres and your liver, etc. She goes through tissue after tissue. She projects the data, the blot actually from the paper with Mike Hemann, the paper that I should have been a coauthor on, she projects it on the screen, but she does some weird freaking dance, where she, instead of describing the long telomeres of laboratory mice as a major bug in the system, she describes it as a happy accident, effectively, because it allows us to test certain things like, âOh, isn't it delightful that they have long telomeres?â And it's like, what the hell are you doing? There is so much riding on correcting this and you're presenting it like itâs just a bonus. And she, in her presentation, she's got several experiments that I did not know she had run that I had suggested to her and I said, you know, things like, âCarol, do you have any idea if a cell has many different telomere lengths, is it the shortest telomere that controls how many reproductions a cell can do?â She's run that experiment. Interesting. Low and behold, it's the shortest telomere. It's a good guess. But anyway, so, she goes through this. There's no mention of me, there's no mention of the actual implications of the the long telomeres for things like science and safety testing and all of that. And I can't seem to raise the issue of the safety question with anybody. Right? At best, I get journalists who are interested until they call somebody, and the somebodies on the other end, I know what they say. They say âeverybody that mice aren't great modelsâ. In fact, there's a paper out there that says something like the mice lie. It's not about this issue. It's just about the fact that mice aren't a perfect match. The issue in question could be solved. It could be addressed thoroughly. And, for all I know, once the JAX Lab figured out what they were doingâ | ||
'''Eric:''' | '''Eric:''' They could change the protocols. | ||
'''Bret:''' | '''Bret:''' For all I know they quietly have fixed this and there was a private, you know, I've heard that there was a private meeting in which they decidedâ | ||
'''Eric:''' | '''Eric:''' Look, this is the thing. Â | ||
'''Bret:''' | '''Bret:''' Yep. Â | ||
'''Eric:''' | '''Eric:''' You see something like this in statistics, everybody knows that most distributions that are bell-shaped are not normal. Right? Â | ||
'''Bret:''' | '''Bret:''' Yup. | ||
'''Eric:''' | '''Eric:''' And on the other hand, we all use normal distributions, and as a result, there are lots of things that at one level everybody knowsâ | ||
'''Bret:''' | '''Bret:''' Yep. Â | ||
'''Eric:''' | '''Eric:''' But don't percolate down to the important layers in which we test things. And I don't know where, like you and I have never been able to fully put together, cause we're not molecular researchers and I'm not even a biologist. How important are these results? How robust are they? Has there been a change? This is a quiet world at some level. Â | ||
'''Bret:''' | '''Bret:''' It's a quiet world. But I think what I have concluded, yeah, working backwards from the phenomenology of the field and how it reacts to this problem, is that there's a tremendous amount resting on failing to acknowledge the error. Even though the error was obviously an honest error to begin with, they would rather sweep it under the rug. I mean, imagine you've got all these knockout mice, right? These knockout mice, there's a major investment in them. It takes a lot of work to knock out a particular gene. Â | ||
'''Eric:''' | '''Eric:''' No, dude, you've got a central, you've got a single point of failureâ | ||
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'''Bret:''' Right. Â | |||
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'''Eric:''' Whose projections are tendrils into everything. | |||
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'''Bret:''' Right? And you've got how many careers built on papers that are now suspect. | |||
 | |||
'''Eric:''' This is like an era. This is like a centralized irreproducibility crisis. | |||
(02:00:37) | (02:00:37) | ||
'''Bret:''' | '''Bret:''' Yes, it's that bad or worse. Â | ||
'''Eric:''' Okay. | '''Eric:''' Okay. Â | ||
'''Bret:''' | '''Bret:''' And, and you know what happens if, let's say somebody hears this podcast and they check into it and they find out, lo and behold, this story is true. Â | ||
'''Eric:''' | '''Eric:''' Yeah. Â | ||
'''Bret:''' | '''Bret:''' Well now the FDA has a problem. Â | ||
'''Eric:''' | '''Eric:''' What would, wait, wait a second. I don't want to get too far out over our skis. We have enough listeners that people will get a chance to hear an unbelievable story. And if there are things in the story that are not true or misremembered or unkind or there've been changes or maybe we don't really fully understand how the drug testing works. I'm open and I, and I want to be very clear, and I want this in the podcast, I'm open to the idea that the most straightforward implications of the story are subject to adjustment. However, having lived the story, I can say that this was an egregious story at multiple points, with conflicts between the evolutionary community, the biomedical community, the professional publishing community. This is a terrible story, and it's also an amazing and beautiful and wonderful story. And you know, I felt really lousy at the beginning of this podcast goading you and prodding you. But I am so bored of you, no offense, as the guy who stood up to the funny kids at Evergreen, and you know, we know what's in the heads of these people. If you're at Evergreen, you're not that good. Â | ||
'''Bret:''' | '''Bret:''' Yep. | ||
'''Eric:''' | '''Eric:''' Right. And that was like, this is the, I just want to be open about it. | ||
(02:02:17) | (02:02:17) | ||
'''Bret:''' No, | '''Bret:''' No, I look, I appreciate it, and I'm glad to have this story out. The story has many different layers of meanings. I know, I remember where I was when I finally sat down to watch Carol Greider's Nobel lecture and I had one of the oddest experiences of my life. I was actually in a hammock watching her lecture, watching her present my hypothesis without my name anywhere on it, and then she projects this image from her paper with Mike Hemann, and I was flooded with two simultaneous emotions that are just completely incompatible. Right? I've never felt anything like it. I was absolutely elated to see my work projected on a Nobel stage, right? That changed me. Â | ||
'''Eric:''' | '''Eric:''' You know I called the horse and rider problem? | ||
'''Bret:''' No. | '''Bret:''' No. | ||
'''Eric:''' | '''Eric:''' The point of the official complex of science is to knock the rider and take the horse, where the horse is the theory and the rider is the attribution. | ||
'''Bret:''' | '''Bret:''' Well, this was it. I was elated and livid simultaneously, and I can still almost feel what it was almost like my body was trying to figure out one half supposed to feel one thing and the other feels the other? But, this story has many levels of importance. Personally, it gave me the abilityâI was already, as you are, very good at not being persuaded by the fact that everybody else disagrees with you, that that has an implication. Every great idea starts with a minority of one and you have to be able to endure being alone with a great idea in order to advance the ball significantly. This story was so extreme and so clear in the end that it just left no doubt. And I must say, I don't know how young students can arrange to confront materials so that if they're really good, they get a clear demonstration like this, that they're really good. So they know to keep going. | ||
(02:04:40) | (02:04:40) | ||
'''Eric:''' Bret, | '''Eric:''' Bret, look, I think you're selfish, and I don't mean to be horrible about it. I think that the story is an inspiration. I've lived the story with you. I have my own version of the story where instead of it being the slide from the paper of Grider and Hemann, it's equations that are known as the Sieberg-Witten equations. And you see what you did, with somebody else putting, you know, putting it up on a board, it starts to change the field, and you suddenly say, you mean I'm not an idiot? Right? And what I'm claiming is that the next layer of this is, âWell, why don't you just submit a paper? If you have ideas, submit a paper, submit a paper, submit a paper.â Who is this fucking suppose to fool? Â | ||
'''Bret:''' | '''Bret:''' Well, right, and this, thisâ | ||
'''Eric:''' | '''Eric:''' I mean, I just, I think the idea is that if you have a seat on the exchange, you know that by submitting a paper, your paper will get reviewed because you have, you present a credible threat. It doesn't occur to you that what you're saying is effectively like âlet them eat cakeâ, to somebody whose paper is going to be reviewed by the person who's, like, holding them back. Â | ||
'''Bret:''' No, | '''Bret:''' No, this is exactlyâwhen Jerry Coyne came at me with, you know, âBret doesn't understand his, his explorer mode stuff is, is nonsenseâ. And then Richard Dawkins echoed it âBret doesn't understand natural selection. And, you know, if he did, he'd submit a paper.â My feeling is, I lived this story, and you're going to pretend that there is even a mechanism to get a proper hearing? Â | ||
'''Eric:''' | '''Eric:''' Look, here's my proposal proposal. All right? Â | ||
'''Bret:''' | '''Bret:''' Yeah. | ||
'''Eric:''' | '''Eric:''' I think that you, Pia. and myself are indicative of an entire layer of GenX academicians, and now probably millennial academicians, whose work was suppressed, and we don't feel comfortable saying these words, which is that the purpose of the university system, in the time that we were there, was in large measure to make sure that big disruptive new ideas did not upset the apple cart because there was the ability to deny, I mean, this is what you guys call interference competition, which is that you keep people from sitting down in the chairs in a game of musical chairs. And then the idea is we have lovely parting gifts for our contestants. Doug Prasher, who did green fluorescent protein, ends up driving a shuttle bus in Huntsville, Alabama, features in the, you know, I don't know, was it the front page of the Science Times? A year later he's still driving a fucking shuttle bus in Huntsville, Alabama. Meanwhile, we're being told that Americans don't care about STEM. We're not really good at science, but thank God, thank God our friends in Asia are amazing at science, because, as bad as our children are thinking for themselves, we've got huge numbers of people who want to come from China, South Korea, India, and Taiwan in order to do the study in the labs, which is actually work, and I'm the guy who found the secret study in 1986 which says, âHey, we're going to have to pay these American academicians over six figures very soon because of the supply demand relationships.â And then they took away the demand curves and they only showed the supply curves. They said this was a demographic rather than an economic analysis, so price and wage certainly didn't enter into it. Like, our problem is that the American scientific enterprise, headquartered in the National Science Foundation, National Academy of Sciences, and our university systems is fraudulent, and it serves to suppress radical new ideas. And I'm not saying that everything is guaranteed to be right about your story, but this is a story that you and Carol should have warred out, in public, without your submitting into a system where you don't know who reviewed this, you don't know how to respond to the comments. You can't measure the delta where somebody in one year says, âthis is crapâ and the next year they say, âthis is my theoryâ. Right? And what I want. I would love to invite Carol Greider onto this program, because I think she deserves the right to rebut what you're saying. | ||
(02:08:58) | (02:08:58) | ||
'''Bret:''' Yup. | '''Bret:''' Yup. That'd be cool. Â | ||
'''Eric:''' | '''Eric:''' And Elizabeth Blackburn is fantastic. I'd love to haveâand these are great scientists. Â | ||
'''Bret:''' | '''Bret:''' Frankly, you're going to say, this is me being too nice. Â | ||
'''Eric:''' | '''Eric:''' Yeah. Â | ||
'''Bret:''' | '''Bret:''' I'd even like Carol to come clean and just put this behind us. I'm not, you know, at this pointâ | ||
'''Eric:''' No, | '''Eric:''' No, it's not a question of that Bret, there isâyou have the right to offer somebody a hand up. Â | ||
'''Bret:''' Yup. | '''Bret:''' Yup. Â | ||
'''Eric:''' | '''Eric:''' But you're skipping the step ofâlet me be bluntâhow many universities offered you a position after you were run out of this crappy Evergreen State College by a weak president who refused to stand up for academic freedom, freedom of speech, and anti-racism, which you exemplified. Â | ||
'''Bret:''' | '''Bret:''' Professorship? Zero. Â | ||
'''Eric:''' | '''Eric:''' How many biology lectures were you invited to give at top tier AAU universities? American Association of Universities? Or, Association of American Universities. | ||
'''Bret:''' | '''Bret:''' None | ||
'''Eric:''' Okay. | '''Eric:''' Okay. What the fuck is that? I mean, let's, let's just say the word âfuckâ a lot, cause I had Andrew Yang in that chair. I don't say fuck a lot. Â | ||
'''Bret:''' | '''Bret:''' Yeah. Â | ||
'''Eric:''' Okay. | '''Eric:''' Okay. So the idea is you have a Maoist insurgency against a student of Dick Alexander, who is supported by George Williams, with support from Leonard Hayflick. He's predicting something from evolutionary theory, registers in molecular biology. It may have drug testing implications, and, like, nothing, silence. And you're terrified to talk about this. Â | ||
'''Bret:''' | '''Bret:''' I don't think I'm terrified to talk about it. Â | ||
'''Eric:''' | '''Eric:''' Well, I'm sorry. Can you tell me something? Where have you toldâ you have a podcast? | ||
'''Bret:''' | '''Bret:''' Yeah. | ||
'''Eric:''' | '''Eric:''' Where is the story written up? Where is the story lodged? You and I have the ability to lodge it. I'm forcing you to do this on my podcast. I haven't heard you do a podcast about this. I hear you talking about free speech. I hear you doing things with the Heterodox Academy. I hear you doing things in the Intellectual Dark Web, something with Andy Ngo, something with Antifa. Okay. The whole purpose of the Intellectual Dark Web is to keep the channel open based on merit, because if we do something like the diversity of ideas, you know, for all I know, the people who are suppressing you are more diverse than you are, you know? Okay. These are ideas that needed to come out. There are health implications potentially of these ideas. This is not ethical to suppress. In effect, it's not ethical for you not to talk about, not to be rude. Â | ||
'''Bret:''' No, no. | '''Bret:''' No, no. Look, I get this. I tried for a decade to get this story to come out. Now, I'm sure I would have been less aggressive on the social front. I would have let Carol go in order to get the story out and get the drug safety issue addressed. I don't know what you regard that as. Maybe that'sâ | ||
'''Eric:''' | '''Eric:''' It's not a question of this. Look, there is a Carol Greider and Elizabeth Blackburn and everybody else in like senescence land, Judith Campisi, who knows. Everybody's got a problem, which is there's way too much transparency, and there's too little funding, and there's not enough autonomy, and there's too much peer review, and for whatever reason, a new game has cropped up where everybody says we need more transparency, more diversity. We need to make sure that we're not wasting taxpayer dollars. We have, you know, ever more oversight. All of this is denaturing our society. We have to compete with China now. We are going to have issues with Iran and Russia, and we are losing our minds because we are serving a baby boom group. Almost, like, you pick a leading university. It is headed currently by a Baby Boomer. That's almost true without even tellingâif I ask you, âHey Bret, pick a university. Don't tell me which one it is.â I will tell you that the number of administrators that that university has soared above the levels of admissions, the tuition has soared above medical inflation, which is above regular inflation. If I ask you about the grant structure, older professors that are winning more grants and younger people are winning fewer grants. This is a giant complex. I am going to have somebody from Sugar Baby University, which is a subset of Seeking Arrangement, because the Baby Boomers made student debt non-dischargeable in bankruptcy. And now this group is offering older men the ability to date younger women with an allowance, right? So we're starting to get into gray area sex work, where the Baby Boomers to keep this lifestyle to which they've become accustomed are effectively enslavingâ | ||
(02:13:44) Â | (02:13:44) | ||
'''Bret:''' | '''Bret:''' Well, they're hoarding wellbeing on every front, including the sexual, which is no surprise at all. Â | ||
'''Eric:''' | '''Eric:''' But hereâs my claim: we are in a holding pattern. I'm in my 50s. You're in your 50s. I've done work that has never seen the light of day. You've done work that's never seen the light of day. Pia has done work that's never seen the light of day. I don't know about Heather. My claim is: it's time to crash land the planes into the control tower. It's enough. Â | ||
'''Bret:''' | '''Bret:''' Wholeheartedly agree. Â | ||
'''Eric:''' Okay. Bret, | '''Eric:''' Okay. Bret, it's been an absolute pleasure having you on. Come back anytime. I want to say that anybody who is misportrayed by this podcast is welcome. We are not claiming to have absolute and universal knowledge. You are more than welcome to correct the story if you have knowledge about this that checks out. But the problem is that this is a story that needs to be told. It's like the story of Margot O'Toole and David Baltimore that played out at MIT, when, I believe that she found that she couldn't reproduce the work of Dr. Imanishi-Kari. And of course the system turned on the person who was trying to say, âHey, I'm seeing irregularities. I'm seeing problems.â Â | ||
We have a biomedical complex that needs whistleblowers. It needs iconoclasts. It needs challengers. The food pyramid has been off for years. Our health recommendations are completely off. I think that this is an essential story. You need to move out of Intellectual Dark Web stuff, which was about keeping the pipe open. Let somebody else do that. And it is time to hire you as a professor at a top tier university. And I'll be happy to talk to you about what happened when you and Richard Dawkins encountered each other on stage in Chicago, because I think in terms of pure evolutionary theory, it is time to boost a young Richard Dawkins who contributed two of the most important ideas in the form of extended phenotype in the mean, which largely dislodges the old Richard Dawkins and his hatred of religion, which has appeared to take over his thinking as regards his own contributions to biology. We got a lot of work to do. Â | |||
'''Bret:''' | '''Bret:''' No question. Â | ||
'''Eric:''' | '''Eric:''' All right, my friend. Â | ||
'''Bret:''' | '''Bret:''' Well, thanks for having me. Â | ||
'''Eric:''' | '''Eric:''' Thanks for coming. You've been through The Portal with Dr. Bret Weinstein, professor in exile from the Evergreen State College. Please subscribe on Apple or on Stitcher or on Spotify, wherever you listen to podcasts, navigate over to our YouTube channel and not only subscribe, but remember to click the bell icon to be notified with our next episode drops. And hope to see you back on the next episode of The Portal. | ||
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