SIO454: Bret Weinstein's Incredibly Curious PhD Thesis

Transcript

This transcript was generated automatically and may contain errors — the audio is the record.

0:00:17 Thomas: And welcome to Serious Inquiries Only. This is episode 454. your host, Thomas Smith. And as promised last episode, if you didn't listen to that, make sure you do. We're going to continue with Dr. Eric Jaffe on Brett Weinstein and dig into his graduate thesis and how in the world he has a PhD in evolutionary biology. And even if that is a legitimate thing he has, it grant him the expertise to opine on vaccines and COVID like he has been. So get ready to dig in. Eric is thorough and went through that PhD thesis and has a lot to say on it. Patrons, I'm going to give you parts two and three smushed together for convenience. Another perk of being on the patreon.com/seriouspod. else still have that little divider. All right. Can't wait for you to hear this. Here we go.

0:01:18 Thomas: We're once again joined by Dr. Eric Jaffe. How you doing, Eric? Good.

0:01:22 Eric: Doing well. How about you?

0:01:23 Thomas: I'm excited to I'm also in the I'm never gonna be tired of and last we spoke in part one his interview with, Bill Maher was so terrible that you did a little digging into his past career and we're curious what you found.

0:01:40 Eric: And I just want to make this point very clear, right? Like I'm not trying to drag anyone just for the sake of dragging. What I'm more trying to elucidate here is that like has a nested hierarchy, right. So when I'm talking about viruses, I have research experience both dealing with viruses, doing molecular assays that involve similar data analysis and experimentation that the virologists will be doing. And then my thesis work dealt in those same molecular waters. Now, I am not going to claim expertise on RNA viruses. I'm not going claim expertise in COVID itself. It does give me a suite of tools that allows me to analyze the data, think about what's happening at a mechanistic level. By that, I mean, what are the genes doing in the COVID virus? What is happening when your immune system reacts? What's happening when you take a vaccine, right? Training and my experience isn't directly applicable to that, but it's adjacent to it. That's really what I wanted to check with Brett, because he was doing a lot of talking about this vaccine efficacy and talking about in -depth experimentation, both in the Bill Maher interview and then in later podcasts. And so I just wanted to see, does that expertise actually match up with what he's saying? Because what he was saying just made no sense to me, if so, I do want to get a couple of caveats out the way, because I am generally not the type of person that likes kind of gleefully tearing someone apart. I do want to just stress that like science is hard, right? Thesis is almost never your best work, right? Actually wouldn't mind starting with what my thesis looked like as like a five -minute baseline just to show what a normal thesis looks like and why this thesis is throwing me through a loop. Now, the reason I'm showing you my thesis is because I want to show not every thesis is good.

0:03:12 Eric: But there's levels to this, right? My thesis was awful. If I'm being honest, there's a reason I'm a high school biology teacher and not studying animal cognition in a lab in MIT, right. I'm not claiming that I'm some super scientist or that I have all the answers. What I do have is a fairly standard looking terrible thesis. It at least shows that I've done the work to show that requisite base set of skills that a molecular biologist and a scientist would have. I've I've got to be honest, I just don't see the same things reading Brett Weinstein's thesis. Now, it's entirely possible that because he is less molecular and he's more of an evolutionary biologist, that I'm missing conventions of the field, that I'm missing key things. But as we go through this, I think I can convince you that like this is a truly bizarre thesis, even accounting for that difference in subfields.

0:03:22 Thomas: Interesting. Right.

0:03:58 Eric: Let me just very briefly talk about what my thesis looked like. And again, I don't think I had a groundbreaking thesis, but mine was about neural And then specifically, what I studied was how does one protein, grainy head like three, contribute to neural tube closure?

0:04:11 Thomas: What? Sorry. These protein names are insane. We had Banjo -Kazooie or whatever. What was it again? Sonic Hedgehog.

0:04:17 Eric: Sonic Hedgehog?

0:04:19 Thomas: Banjo -Kazooie would be a better one. What was that one you just said?

0:04:23 Eric: Graony head. And it was named because it was found, of course, by fly researchers and fly researchers are always out of pocket with their naming. Naming, but basically it's a skin gene, right? It helps form skin barriers during development. And so when the flies didn't have this gene, they would have what looked like a grainy head because they weren't forming continuous barriers, right.

0:04:43 Thomas: Interesting.

0:04:44 Eric: That's the name of the gene. And in my thesis, what I tried to do is I tried To see what this gene is doing in a very specific tissue as our neural tube closes, right, a neural tube is what forms our brain and spinal final initially. Column I had one major hypothesis. Major hypothesis was that grainy head, like three, the protein I'm studying works to give cells their identity, right? Remember how we talked about how cells have to differentiate and find their calling, whether they're a skin cell or a stomach cell. Was thinking that grainy had like three was a shepherd in this process.

0:05:12 Thomas: Your cell dads are like, you should get a degree that actually matters. Come on.

0:05:16 Eric: And right, that really influential professor or something that's telling the cells at this region of the neural tube, you need to become skin cells, not neural cells, And right? In order to test that, I had to do experiments, right. So what I did first to test that hypothesis was I bred my own mice with the help of some wonderful people in the lab, I never want to take full credit for things that weren't, you know, fully me. And I bred one set of mice with The Gene, and one set of mice that didn't have The Gene right, and they were completely identical. Then I would compare what those cell tissues looked like at various points in development, both right before the neural tube defect is found, and then right after those mice fail to close their neural tube, right? Then, I can look at the identity of those cells in those tissues using different assays.

0:06:02 Thomas: That's the second time you've said that. What is that?

0:06:04 Eric: An assay is like a, a simple version of an experiment, right, it is the thing you are doing in your experiment. So, like one One assay would be what we call immunofluorescence, where I would label proteins in tissue with antibodies based on their identity, right? Skin cells produce different proteins than neural cells, right, so I would try to prove that these cells either maintain their normal skin cell identity or in the mutants they switch to a different identity, that's only one way to prove that, right. So I also looked at the RNA, the thing that makes the protein, gives the instructions, And I said, in my mutants, is the RNA levels of these key proteins exactly the same? Are the genes instructing these cells to produce the right identity at the right time, right? That was not the right answer. So then I went to the next step. Now, notice how I keep getting more and more narrow in my experimentation, right. I know it's not identity. So now I had a second sub -hypothesis. I think it was working to turn on this set of genes that regulate the kind of rope in our cells called active. It. There I looked in a microscope, A right? Really powerful microscope called an electron microscope. I looked at the types of structures that were being formed on the cell membranes between my mutants, the ones without grainy head like three and the ones with grainy head like four. And I saw two major things. Is as you went from cranial closure to caudal closure, from right the head to the spine, the spine kept using different types of cellular projections, different shapes on that cell membrane to kind of reach across and sew the body together, right? In my mutants, they were even more weird than the normal mice. So

0:07:28 Thomas: Don't want to be the PC police, but I feel like there's got to be a better term. These poor mice are like... Come on! Mutants? We're not mutants, sir.

0:07:35 Eric: You want to be complimentary, I guess you could call them a knockout. So these knockouts, beautiful, beautiful mice that just happen to sometimes have spina bifida, right, these knockout mice, which means that they don't have that version of the gene, would have different cellular projections than the other ones. And that led to my model, that they were working upstream of a very particular protein protein to regulate the formation of these little things on the cell membrane, right? Here's where I would admit that my thesis was not the best. An ideal world, I would have fully fleshed out that mechanism, right, I Would have proven definitively that grainy head like three works, what we call upstream, it directs the activity of these actin regulators to close the neural tube properly. I actually didn't finish that story. I had good preliminary data. But again, because I'm a biology teacher now instead of a scientist, the main reason for that is because my hands were not where my brain was. And sometimes science is more art than science. So I actually like rarely had the fine motor function I needed to do these complex, delicate experiments in the embryo.

0:08:34 Thomas: That's what it comes down to? Huh.

0:08:35 Eric: Lot of times it can, yes. Yes. So what I had to finish my thesis was a proposed mechanism, some preliminary data, then the more real data that showed the concrete phenotype, right? Notice how I started with a broad question. How do we sew our neural tube? The end of that story, I was talking about one gene regulating one protein in one very specific tissue, right. Along the way, I had do those assays, those experiments, I have to analyze data. Data. That's the key in your thesis that should be showing you that you are a scientist. Can you come up with a hypothesis? Can you design the correct experiments that analyze that hypothesis? And then can you make reasonable conclusions based on the results of those experiments? Sometimes you get really elegant theses where everything works and you have truly groundbreaking stuff. A lot of them look a lot more like mine, right? It gets a little muddled at the end. Maybe you don't complete it with quite as nice a bow as you wanted to, to, but you're doing the basic stuff that a laboratory scientist is doing in a research project, right? I wanted to use that as the grounding for as we talk about Brett Weinstein's thesis.

0:09:35 Thomas: Very interesting. Did Did anyone answer that question? That's interesting.

0:09:39 Eric: Be honest, like the gene that I studied in neural tube closure is one of the most studied for, it was actually the first gene ever implicated in neural cube defects. So I was kind of picking up like the last pieces of a project that was getting less and less interesting. And I think someone saw the tugboat right on the shore and didn't think it was worth their time to fully pull it to shore. The main point being, right, my thesis, I'm doing experiments, I'm analyzing data, and I'm assessing my hypotheses and coming to conclusions and models, right?

0:10:07 Thomas: I think I get all that. What I want to know for context going into this is how much is going to vary by, again, the exact field and subfield you're in, maybe even the institution you're at. So can you refresh us, like, you were doing versus what Brett Weinstein was doing?

0:10:23 Eric: And that's a very good question. And it's one of the caveats I want to give, right. I am very clearly from the more molecular side of things. And Brett is very clearly from the more Darwinian, big picture side of things, right? But that being said, there are certain things you would expect to do in science that we will get into that are universal across subfields. Things like using experiments and testing predictions, right, data sets, things like that are common to all thesis, regardless regardless of your subfield. Now, I'm open to the idea that there is something about this department and this particular subfield field that might not follow that paradigm. But I would almost say it doesn't matter at that case, because if your field is so different that you are not speaking that general structure and language of biology, then you shouldn't be commenting on COVID, which does use that structure and language, right? It's almost immaterial. And this is my main point. I'm not doing this to drag Brett Weinstein. I am doing this show that what he is doing when talking about COVID is not not speaking from a place of expertise. Does

0:11:06 Thomas: That's a good point. Yeah. I'm curious then get into whatever he was doing kind of along the same, you or framework that you were talking about your thesis.

0:11:28 Eric: Already where it starts to get confusing for me, if I'm being honest. Topic is a lot more broad.

0:11:33 Thomas: Okay. Where did he go? Remind us, where did he go? What was he specifically, you

0:11:37 Eric: He studied evolutionary biology at the University of Michigan. And what he, under Richard Alexander, but again, I want to be very clear, I don't know the structure of the lab. I don'T know Richard Alexander's involvement. I DON'T know how that individual department works. All I have is the the end result of his thesis to look at. I do want to give that caveat.

0:11:57 Thomas: This is reminding me of when we, on Where There's Woke, looked into the master's thesis that Jordan Peterson was touting that a student did. Wait, Wait, did you listen to this?

0:12:06 Eric: I actually did listen to that episode.

0:12:07 Thomas: Man.

0:12:07 Eric: And I was going to say that one doesn't prepare you for this one. Because what you were analyzing that master's thesis, there was tons of stuff for you to dive into.

0:12:15 Thomas: Yeah. And it was also about how much they were talking about it in a way that was inaccurate. So different things, but I just wanted to mention it because if you haven't heard that, go listen to those episodes because it is, wow wild ride

0:12:26 Eric: They were wonderful episodes. And I want to stress the differences. This one, we're not going to be talking about the inaccuracies or lack of clarity of thinking. I think on a lot lot of places, he actually shows really good thinking about evolutionary biology. We're really going to be talking about is how different this looks from the type of science that I'm used to seeing in a thesis, and maybe we'll work through it together. Without giving spoilers, through each chapter, I kept expecting one thing and then seeing the zag into other things in surprising ways. Start diving into it. Starts off talking about what his overall all topic is. And what Brett Weinstein studied for his thesis is a really interesting topic, and that's trade -offs. Now, when we're talking about trade -off in evolutionary theory, what we're really talking about is, and this will be in a future Seriously Awful Movies, but it's the raptors in Jurassic World, right? They can't both be strong and fast at the same time. Their bones shouldn't allow for that, right. They're really, really intelligent, that's going to come at a a resource cost to something else in their body. But the raptors in Jurassic World don't have any of those trade -offs. They are basically perfect hunting machines, right? What Weinstein does, and I actually think this is really interesting, is he thinks about how these trade -off will affect evolutionary processes and different events, right. So he comes up with three major chapters that he's going to go through. Of all, I should mention, he mentions three major types of trade -offs. The first one is a probabilistic trade -off. Probabilist trade - off, you can think of this as it is unlikely that someone will both be really, really, really tall, like top 1 % in the world at being tall, and one of the top 1 % in the world at be an artist. Unlikely to see a 7 '7 movie star. The reason why isn't because they're necessarily working against each other. Just the odds of that happening in both of those tails of the population.

0:14:12 Thomas: Star might be a different story because I think height could factor into that for certain ways but you're saying if there are two totally independent variables the odds of being in the extremes of both is obviously just mathematically lower roots

0:14:15 Eric: Fair. Yes. Exactly. And he considers that the weakest type of trade -off. And I would actually agree with that. Second one would be that we have those limited resources, right? There's an allocation of resources that's mutually exclusive. Of this as the example he uses in the thesis is a plant can either focus on growing at the roots or growing at shoots, right. It can either grow up or grow down, but it takes a lot of resources to grow in both directions.

0:14:47 Thomas: Or shoots that's what I always say that's that why that's common saying from my my grandma. Hey, roots are shit. I don't know.

0:14:52 Eric: See, I just shoot for the roots, and then you're just doing it well in both ways. Point being, that's another type, right?

0:14:58 Thomas: Okay.

0:14:58 Eric: And then the last one, and the main focus of his thesis is ones that are based on design limitations, right, that's the raptors, it's very hard to get a bone that is both very, very agile, and very, very durable, right. Either going to have light skeletons that are very agile or thick, heavy skeletons that are very, very durable. And that's the main type of trade -off that he's going to focus on in his thesis. All of this so far is good, right?

0:15:23 Thomas: I would say it's interesting to be so general. It's not like, like in this is just me going, a very limited experience, but I've had a lot of people on to talk about different studies and et cetera, et cetera. And I know a few theses. It feels like they're normally hyper -specific. Like, like yours. I can't even repeat what it was. Cause it was like, does this one thingamajig cause a thingamajig to whatever in this very specific thing it is interesting right now to be like trade -offs in general it sounds like a very big topic but I also don't know that that's like necessarily you bad or anything just strikes me as different hmm

0:15:57 Eric: I actually think you did pick up on something. So that was actually something that I picked up on was it's going to be very hard to provide thesis quality work for such an overbroad topic. There's a major filtering event in your graduate school career called your qualifying or your comps exam, where you basically propose your thesis. One of the major things you get docked for in proposing your thesis is that it's either overbroad or over -challenging, right? They want you to be able to complete your thesis in the time of your PhD. Without too many spoilers, this thesis reads to me like one that is overbroid, that precluded him from drilling down and finishing any of his what we call aims, right, any of His individual sub things that he wants to investigate. I actually think if he drilled down on one of his four chapters, and really did it properly, is a very good thesis in here somewhere. Let's talk about what I mean by that. So in chapter one he's going to do a very brief overview of just design trade -offs in general and those three theoretical things. That is completely normal for a thesis, right. Your chapter one is your background information, it's your context, it is describing what you're going going to study. Two, and this all sounds great in the introduction. I want to be clear, reading the abstract, none of this kind of tripped my wires other than that overbroad concern that you brought up. But in chapter two, he's going to describe a very cool trade -off that he proposes where mice, right, animals in general have to make a choice. And by choice, I'm using that anthropomorphically, right? Obviously, evolution doesn't actually have conscious decisions, But

0:16:24 Thomas: Wait Sure.

0:17:27 Eric: Got to make a choice between either having really good maintenance of tissues and long life or starting to end that program of self -maintenance, right? That you're not risking more and more cancer. Because in his kind of framework, the more cell divisions you're doing, the More you're able to keep proliferating, the the more chances you have to accrue mutations, the more chances you'll have to drive cancer.

0:17:49 Thomas: Interesting.

0:17:49 Eric: Again, I actually have very little, you know, very little that I would brook argument with in that initial proposal, right? Here's where he starts to lose me, though. In chapter three, he goes from that, which is a perfectly good question to launch into your thesis about, into chapter three is talking about kind happens to ecosystems as we go from really good conditions, right? Places where we're in times of plenty versus what happens when the ecosystem reaches times of scarcity, right? And what that does to diversity and what that Does to the forms and functions in these design trade -offs that animals have to make throughout their evolution, right. So by this, I mean, if I'm a bird, and right, I'm in times Of scarcity, I'm going to have a type of beak that can eat lots of different foods, right food is scarce. I don't know where I'm getting my next meal. So I'm trying to eat seeds. I'm trying to eating bugs. I am trying to eat small animals and I need a beak that can handle all of those different food sources, right? If I'm in times of plenty where there's food everywhere, also going to be lots of animals that can support, right.

0:18:49 Eric: And that's going to increase competition but also I can rely on just one food and there's more than enough of that one food type, right? I am going to leave my generalist style and instead of competing with with everyone for everything, I'm going to compete with a small subset for a small subset, right? Gonna go back to being a small fish in a small pond, as opposed to trying to be in that big pond of competition. That make sense? Again, that's a perfectly reasonable thing to study. I would argue it doesn't build well off chapter one. And it's kind of showing that he's looking for this. And I don't want to, get you too far in his head. But I think it does leave bread trails to the type of science communicator who will become. It looks like he's searching for an overbroad grand theory of everything that explains things a little too neatly, right?

0:19:31 Eric: I just want to put a pin in that.

0:19:31 Thomas: That's interesting, yeah hmm.

0:19:33 Eric: Chapter three is where he kicks that into overdraft, sorry, chapter four, because that's the third thing he studies. Chapter four, he is basically going to try and argue for a naturalistic evolutionary theory or development of game theory, right? Do humans hold to their morals some of the time and not others? Not what gives them their morals, but why do they hold to their morals at certain times?

0:19:56 Thomas: Does that have to do with where we started?

0:19:59 Eric: One of these sections, right, any one of these chapters could have been blown out into a reasonable thesis by themselves. But I'm going to argue that trying to do all three at once shows uncareful thinking, thinking, a lack of scientific rigor and that propensity to try and come up with grand theories as opposed to doing the job of a scientist.

0:20:15 Thomas: And and I'll be honest one pattern and you don't have to co -sign on this but just for me personally I've noticed the pattern with these people tends is a huge factor. And I don't mean diagnosing them as pathologically narcissistic per se, but like a tendency towards narcissism, I've noticed in a lot of these guru type people. I think it leads people to believe they know more than everyone else and therefore get stuck down these cognitive bad traps of not their their own stuff enough and not anyway all that is to say the idea that would be able to say something novel in all these big different areas of these chapters to me strikes me as a little bit narcissistic or at the very least arrogant kind do you think is that valid or no sure

0:21:01 Eric: Want to be a little careful because obviously I'm not inside his head, but I think that you are onto something there. And there's a way that he writes even in this thesis that to be honest, reads less like scientific writing and more like a pop science book. That to me shows again, that like, it's already kind of thinking of him him as like that central explainer as opposed to the researcher, if that makes sense.

0:21:21 Thomas: And keeping in mind the context in which I got to To know Brett Weinstein from a distance was him not being able to listen when it came to discussions of race and having to lead the conversation like that was the my not going to go rehash it now. Now, maybe I kind of do want to rehash it on WTW sometime, but the central problem with that guy, and this happens with a lot of almost all of these things, when people essentially have a tantrum and lose it over like what they call the woke students going amok is usually their inability to just, even if you don't want to listen to just not leading everything. Thing like he insisted they couldn't have a day of absence at uh because that's that's racist but if anyone wanted to attend his seminar and listen to him talk about evolutionary biology and race that would be excellent and I just found it so unbelievably arrogant to think like that's the only acceptable thing here is if people are listening to him he can't listen to anyone else.

0:22:20 Eric: I give you a great example from the introduction?

0:22:22 Thomas: Sure.

0:22:23 Eric: Here's a sentence. Solution to the problem of trade offs obscured by complexity, So right? He's saying like, biology is a complex thing and to step out of the traditional boundaries of biology and into parallel realms in which trade offs are better understood.

0:22:35 Thomas: What?

0:22:36 Eric: Engineers, for example, work with trade offs on a daily basis. And it's quite common to hear agreement among them regarding principles, even laws that have of equal reason to be expected in biology. I'm not sure why he goes on a page long tangent engineering, right? There is a lot of good research about design trade -offs already in the biological literature, some of which he already cites.

0:22:57 Thomas: Yeah. And that just seems like a very basic thing. Like giving me what sounds like a Very Basic Obvious Point disguised as though he's brilliant for having thought of it.

0:23:06 Eric: There is lot of that in here. And again, I'm trying not to get too much in his head, but like all I can do is read what's written and a lot if it reads like that. If we keep going, right, starts giving examples of trade -offs. And here's a good example of what I mean by this. He says, suppose, for example, that a female frog prefers males that are unusually large and at the same time males that are usually blue. And suppose that further that size and color are largely independent polygenic traits. From the female's perspective, preference for large size and blue color are likely to trade off against each other. A perfectly fine example. What I don't get is there's literature. Should be able to find literature cited examples of these trade -off and use real data, real examples. You don't need to use hypotheticals in your thesis. You should be combing the literature for finding those cited examples.

0:23:50 Thomas: I would think a thesis advisor would want to see that.

0:23:54 Eric: He then goes on to predict what the consequence would be. But again, you don't have to use a hypothetical consequence of that difficult time finding individuals with both large size and color. You should being able to find those in the wild, right? There should be data that shows that you are not seeing these two -tailed selections. That's my big problem with this thesis. A lot of times I have comments that just say, show me some data or do the test. Because what he does is he poses these weird hypotheticals, not weird, they're relevant hypotheticals. But they're unnecessary in the context of academic literature, because you should be doing the work to find that, right? I go, suppose, for example, there's a cell that produces actin in GEF -19. Would not say that in my thesis. What I would do is I would say, and in this context, cells have been shown to produce actin upstream of the activator GEF -19. And then I would cite the experiment that actually

0:24:44 Thomas: Sounds

0:24:45 Eric: Proved that, right? Difference being, I don't have to speculate. Exactly. He then does give a cited example of these design trade -offs, right. So he brings up that root and shoot example. Now I'll be honest. I was expecting that to be his example, because at some point in your thesis, you want to switch from cited examples to things that you have done personally, right, some point, it no longer can be literature review, and it has to be your own experimentation. Make sense?

0:24:47 Thomas: Sounds like doing work. Yeah. Oh, yeah, of course.

0:25:14 Eric: He cites another example, And right? This is from a paper. And again, in the introduction, it is completely fine to cite other examples. What I was expecting him to do is pivot from that example about roots and shoots to system that he studied in order to come up with similar models and conclusions, right. I talk about GEF -19 in a certain cell type in my paper, I'm setting up that I'm testing that same protein with my own hands in my own cell lines. Does that make sense? I'm not just citing their work. I'm using it as a springboard into my work. He keeps going with this root and shoot trade -off, right? Then he just kind of leaves it. He doesn't go to his system. He goes to another example of mechanical engineering, like the plight of a photographer trying to capture a picture, right. So, he did a great great job citing a biological thing and showing proof of principle, proof of concept that you can talk about biology in the context of these trade -offs and that there is literature cited in the field about this, right? Is no reason to go back to the well about kind mechanical stuff, but

0:26:10 Eric: That's fine. Then ends this stuff, right, saying the most important aspect of design -constrained trade -off is that they are insensitive to resource supplementation and thus produce hard limits on what selection can and cannot do. This is actually a really good sentence, right? It's a clear summation of why design constraints, right, that bone being either durable or agile doesn't get fixed by just giving the raptor more food, right.

0:26:33 Thomas: Okay, gotcha, yeah that makes sense.

0:26:35 Eric: Here's the thing, he's not showing me that experiment. So what he should have at the end of that sentence is the paper that does show that, should right come with the citation, and not just his work. If you want to tell me that design constraint trade offs is insensitive to resource supplementation, either test it or show me who did test it. I believe it. It is perfectly plausible, but it is not proving it. Does that make sense?

0:26:57 Thomas: Yeah I mean that's kind of what we're doing here in a thesis I would think.

0:27:00 Eric: Exactly, right? This is a perfect opportunity to design his own experiment, right. Could design a situation where he's both supplementing and not supplementing resources in a population that's controlled for these genetics, right, and he can show that even if you rescue the resource supplementation, if you're brittle boned, you're not all of a sudden going to be both quick and durable. And if you're durable, you're not all sudden going be both. Quick and durable, right? You're not going to rescue the thing you're deficit in just by supplementing with more food. So that's an easy to do experiment that he could have done in the lab. Don't know why it's not done. Okay. So another weird thing is he goes on to say, talking about these designs, constraints, uh, right. And this is getting to what you were talking about. Are in a sense, the primary geological force acting on the adaptive landscape. Metaphor of Mount Improbable may explain how simple processes can produce instances of mind -boggling complexity, but design constraints are the reason Mount Impprobable takes the shape it does, why creatures don't rise forever toward functional perfection. Is a big statement to have without any citations, is a lot that he just said with zero academic literature. And I think it's a little alarming that the thing he does cite is a pop science book. I

0:28:11 Eric: Am not saying that all pop science is bad. There's a lot of really good pop science where doesn't belong is in your thesis. We keep going, right? He starts listing more examples of these key design constraint trade -offs. Here's another great example of something that he could have done, right. Says, let's start with the evolution of flight in bats from a gliding ancestor to a true power flight, right, says true power flight is superior to gliding in many regards. A flyer is both more agile and more efficient than a glider. But between agility and efficiency, there is a well -established tradeoff. If there is are well - established tradeoff, what should I expect to see right there?

0:28:47 Thomas: Establishment of that trade -off through Through science?

0:28:49 Eric: Exactly. Then he goes on to continue that analogy, the birds. Right. And he ends up by saying and it stands to reason that the emergence of power flight, light, trait a would initially have been crude, both inefficient and clumsy, right? Things I take issue with there. Efficient does not always mean the same thing in every context, right? And if you're using it very purposefully in this type of field, you should probably define what you mean by efficiency. Because I efficiency could imagine to mean speed. I could imagine it to mean not using a lot of energy. I can imagine it mean starting and stopping very very quickly coming very quickly in the bird's lifespan, right? There's a lot of different ways that efficiency could be met. No definition there, which again, I would say just points to a lack of carefulness in thinking about it. But the main point is he says, and it stands to reason that the emergence of powered flight would have been crude, efficient, and clumsy. He was truly interested in answering this question and he made this the focus of his thesis, he could have went into the fossil record. He could have talked to biomechanicists, right. There are people that actively study this, there are things that you can learn in the literature that directly addresses this. You don't have to treat this as a hypothetical and it stands to reason.

0:29:58 Thomas: Seems more like a paper you wrote, maybe, kind an actual thesis.

0:30:03 Eric: Not, it would be a paper if it was the actual data going into the fossil record, right? Seems more like a white paper than an academic paper, where you're kind of bouncing ideas and brainstorming, but you haven't yet done the rigorous work to validate those ideas, right. Even goes on to to say, the intermediates would have been increasingly agile and efficient, and on average, each generation slightly more so. We have fossil records that show a pretty, right, we kind of sketched through this in our last episode.

0:30:28 Eric: There is a pretty complete fossil record of birds, dinosaurs, and the evolution of flight. Should be able to cross validate this in And the fact that he's not doing that is weird. Goes back to mechanicals, then drawing this analogy between the right flyer. And here he does describe all of the different stages at the right flyer, right? The evolution of airplanes go through. Why are you not doing that with the actual biological example though? The first problem, he right says to kind of put a bow on his stuff, right. The above arguments, design constraint trade -offs become the most profitable focus for a biologist. Patterns should we expect of design trade -off in complex entities? To me was the first time he very clearly described what his thesis is going to address?

0:31:09 Thomas: Yeah. Yeah. I was going to actually ask that, but okay. Maybe you've answered it.

0:31:14 Eric: This, I would still say it's overbroad, right? I would look at one individual design trade -off. I would focus on the evolution of flight and bats, the evolution of flight in birds, that root to shoot thing, Look right. At one system and truly do that well. Nevertheless, I actually do think this is a pretty clear summation of what he's doing, even if it's overboard, right here's where we go back to, um, you're saying there's a a little bit of narcissistic, right? Talks about this claim about how these trade -offs are kind of a good framing for biology, right. And he says, this claim strikes, many biologists as a bridge too far. There being no intuitive currency to the idea that coat color should negatively impact speed, for example. What he's saying there is like biologists aren't being careful enough and thinking like, well, maybe the darker coat color absorbs more heat, which will affect the amount of energy you have to use in your metabolism, right? And that'll affect the size that the animal reaches. But I assure you, Brett Weinstein, scientists are thinking about this stuff.

0:31:48 Thomas: What? Yeah.

0:32:08 Eric: It's a question of whether the magnitude and scale shows up in the data.

0:32:07 Thomas: Yeah. I would think so. Plus, Plus, does he provide any for that? Really he just said many biologists are you know not doing a good job essentially but you don't like at the very least even with references that'd be a little rough for a thesis to be like that arrogant but like no references huh yeah

0:32:15 Eric: No, no. Yes. Also doesn't cite first organisms are never optimized for a single task, but instead must succeed in at least several ways to pass on their genes at all. That's something you probably probably want to cite. Some trade -offs involve inherent negative relationships, but with bargain at one end, such as evolution clumps all creatures at the same end. Again, just give examples. There are things in the literature that can prove your point and not keep this theoretical. This goes back to what I was talking about in part one with the COVID stuff, right? Does all of this high -minded evolutionary biology talk, but he doesn't ground it in real world examples, and that causes it to become overbroad, overgeneralized, and not really applicable to the systems he's actually discussing. Let's kind of go past the introduction and let's get into what his three chapters are, okay? Are going to talk about first a paper, and this is the paper where every time I have confusingly brought up Brett Weinstein in online discussions, they say this is is the seminal paper that like really put him on the map as a biologist, right? The one that like shows his ability and facility as a Biologist. Now, I could not read it for a while because I didn't realize it was chapter two of his thesis, and it was behind a paywall. Now that I know it's chapter two, I can dive into it.

0:33:29 Thomas: Okay okay oh wait really that so did he republish it later or like

0:33:45 Eric: So typically, and I actually didn't mention this, a lot of theses are end up being just staples of a lot if you're published papers, right, You have an introduction that kind of grounds what you're about to present. You have a middle set of chapters that are your kind of published papers and your results, and then a discussion and conclusion at the end that kind of shows your working models, ties everything together.

0:34:04 Thomas: You've already published a bunch when you you write your thesis oh

0:34:07 Eric: So what your thesis is, your thesis is actually the end of your project where you've already demonstrated that you've done the work needed to be a scientist. Kind of you should not be writing your thesis and defending unless your PI has already already told you, you have papers published, you are ready to graduate, you have like a 99 % chance pass of passing your thesis. Do not start your thesis until it's ready, which makes this thesis even weirder, but we'll get into that as we start getting into the actual meat, right? Because so far, we've only done the introduction. It's entirely possible that he has just been burying the lead and his actual experiments and systems are in the actual chapters, right. So we're going to start with his first analysis. That involves a hypothesis that cancer, rather than being the effects of aging, right, and the effects of your body shutting down, is the opposite of that. And I somewhat agree with this, actually. I think you can often think of cancer, and I would actually love to do an episode on kind of what cancer is and why there's no cure for cancers. But you can really think of canter as just when developmental biology happens in adult tissues, right? When instead of having normal adult, what we call settled cells, where they're no longer dividing, they're They're no longer kind They become more like those stem cells that you have in the beginning where they're constantly growing, constantly dividing. They lose some of their normal identity. So I'm okay with like thinking of cancer as being the opposite of what we call senescence, which is that like winding down of division. That kind of, you can think of senesence as the restaurant isn't quite closed yet, but they're no long accepting new customers, right?

0:34:56 Thomas: Interesting okay uh

0:35:36 Eric: They've already done their last seating. They know they are on the way out. They're kind of getting organized for closing time whereas cancer is like if it was about to be closing time and all of a sudden you put we're now open 24 hours a day and everyone is welcome there is no line to be um does that make sense so

0:35:53 Thomas: Think I understand the point he's making but yeah I'm just I'm sure the analogy so you're saying uh cells that are like that are cancer cancer cells are, there's a mismatch between what the phase they should be in and what the phase they're acting like they're in. Right.

0:36:10 Eric: They they are grown -ass cells acting like college kids, right? Whereas senescent cells, they have already started to go to bed at nine. They're no longer dividing and reproducing.

0:36:20 Thomas: So it's more, yeah. So, it's like there isn't a production of a high school or college theater getting out and coming to dine at your Denny's, but you're acting as though there is. Like you're just cooking a bunch of shit, though there isn't the neat, you're in the wrong phase for it. I think that's, okay.

0:36:36 Eric: You, right. Exactly.

0:36:38 Thomas: Sorry, not quite being perfect.

0:36:41 Eric: No, now that works perfectly. Right. You're cooking food for customers that shouldn't and wouldn't be there.

0:36:45 Thomas: That aren't there. Yeah. Okay.

0:36:47 Eric: Yes. So he publishes this paper that is pretty interesting, right, what he basically argues is that lab mice are really bad for studying aging because they're protected from the environment. And what he proposes is that cancer and the senescence are in opposition to in particular, what regulates whether we are more in that active stage where we're proliferating and courting cancer, or we're in that senescent stage where we're no longer dividing and risking getting more cancer cells is this thing at the end of our chromosomes called telomeres. You ever heard of telomere before?

0:36:58 Thomas: I have heard of telomere, but I don't remember exactly what it is.

0:37:23 Eric: Telomeres are, are the ends of our chromosomes. DNA can only replicate in one direction, right?

0:37:29 Thomas: That I don't understand.

0:37:31 Eric: It's based on the structure of the molecule. It can only go in.

0:37:33 Thomas: Do you mean like a physical direction or a metaphorical direct?

0:37:36 Eric: Yes. In a physical, no, I actually do mean in a physical direction. If you were to look at a structure of DNA, you can label all of the carbons in the sugar backbone, right? From one to five.

0:37:48 Thomas: Sugar backbone.

0:37:50 Eric: So DNA is made of two things. And we'll talk about this when we talk about how genes work, but DNA is Made of a sugar backbone. And then the base, right, the ACTG that gives it identity. The way it connects from one base to the other going up and down the double helix is using that sugar backbone and they connect at very specific carbons. Replication can only go in one one direction down that backbone. So it can only go from the five prime carbon, that top prop carbon to the bottom carbon, the three prime carbon. It can't go in the reverse direction, but that means at the end of your chromosomes, you'll have a place where you can't attach the DNA polymerase to replicate the DNA. So your ends of your chromasomes are constantly being shortened after every time your cell divides, so what he's trying to argue is that the length of those telomeres, right, how many divisions you have is directly related to your capacity for both aging and cancer. So what he argues is that because mice kept in labs don't have to constantly divide their cells to repair tissues, right? They're not constantly doing the maintenance and stuff that we do in our bodies because they're kept in these pristine environments, they're going to be over good at resisting things like cancer and disease of aging pathologies, right? That make them a poor model for studying disease and aging because they don't have the same aging mechanisms. Does that make sense?

0:39:14 Thomas: I have no way of evaluating that per se, but sounds plausible from what you're saying.

0:39:19 Eric: So, so far we are fine, right. What he's basically saying is we want to investigate this this design trade -off. Shortened telomeres come with that decreased risk or does shortened telomeres come in shorter lived animals that don't have to worry as much about aging, right? His argument is that lab mice don't need to worry about aging because they are constantly being killed after eight months of breeding, right. Whereas if you're in the wild, you have to have really good cell maintenance programs to deal with the environment, right, it's not that selection stops working on you as you get older, it's that you eventually have to make a choice. If you keep dividing and keep having this maintenance program, you risk more and more cancer cells developing in the body. That make sense?

0:39:59 Thomas: Okay?

0:40:00 Eric: Eventually you want to shut down those cells and make sure that you're no longer courting cancer and you're just kind of getting ready to hold what you have, So you're no longer really doing the maintenance programs. That's why a 30 -year -old doesn't heal as quickly as a 20 -year -old, right? You're no longer doing as much. You don't have as many cells in reserve to repair the tissue. And as the tissue gets more and more damaged, you start courting cancer more and More. This actually dovetails nicely with a shout out to Dr. James DeGregory from University of Colorado. He was a professor of mine that had this theory that a lot of mutations in cancer happen very early in life, but it's only as you start smoking and develop hypoxia, as you get inflammation from many different types of chemical and physical wounds, right? The microenvironment, the selective landscape for cells, goes away from healthy cells and more toward cancer cells. This is a very similar model that Brett Weinstein's proposed, right. So I do want to point out one thing. Is how he started this chapter. Does not read like science to me. Introduction. Do we get tumors? And why do we grow old? These questions have become an obsession in the biomedical community. We view them as pieces of a much larger puzzle. How is it possible for a highly differentiated, self -repairing organism composed of millions, billions, or trillions of cells to live long enough in a mutagenic environment to reproduce without a single cell escaping the normal developmental program and becoming a deadly tumor, right? So that's basically sketching out what I just said,

0:40:14 Thomas: Interesting. Okay.

0:41:21 Eric: But that's really not how science writes in a thesis, right, that is the stuff of prose and kind of pop science books. Just want to point that out real quick.

0:41:29 Thomas: It sounds like he's trying to hook in his readers on his blog or something. Thing.

0:41:35 Eric: Now he starts going on about the data in these lab mice, but here's where I take issue, right? Issue is, is that he's not actually doing the experiments himself, is he actually going through and doing a systematic kind of meta analysis, right. He's doing is giving examples, but never kind bow on it. So let me kind of sketch out what I mean by that, right? He'll do is he will say stuff like, where Giant tortoises housed in protective shells and living on remote islands face few hazards during their reproductive lives, producing a rate of senescence that is almost imperceptible. One, there is zero citation for that. That is a perfectly good observation. What I would expect to see is him saying something like, and as a result, I can design an experiment that mirrors this observation in the lab, right? You can show that the very low probability of future reproductive opportunities yields differences in how the body develops over time, right. To keep going, he says, when this first trade -off, right, this kind of idea that senescence, is that shutting down, that aging of the cells comes in direct opposition to adding onto those telomeres and kind of having that ability to repair tissue, but courting cancer, right? That's the main trade -offs we're going to keep in our head at all times. Do we add more telomères onto our chromosomes so that we can repair tissues, but we court cancer with each division? Or do we stop repairing the tissues so that we no longer court cancer, right? He says, no clear case of senescence causing plyotropy that has come to light invertebrates. This is an odd view,

0:43:02 Thomas: Sorry.

0:43:02 Eric: Right.

0:43:03 Thomas: You might have to explain that. There's no clear case of what?

0:43:05 Eric: Those maintenance trade -offs coming to bear later in life, right, that the tissue maintenance that we do early has that trade -off later. Later. I'm a little confused by that because I actually think you could use oxidative stress and inflammation, right? Things that we do from our metabolism as a good example of the things that we need that are required for metabolism, for reproduction, for energy, right, things that do cause that cellular damage and stress later in life as a necessary trade -off, right. Need oxygen to accept that terminal electron, but that free electron that that oxygen accepts then damages our tissue.

0:43:40 Thomas: Interesting.

0:43:41 Eric: That's why taking antioxidants is so important. Then we get to a section, right? That actually starts perking my interest. And it says telomeres and senescence, right. So we're getting to that main kind of, it Says the experimental approach. So now my ears are perked up, right, we're finally getting to That experimental approach, and he starts detailing this experiment that was done in 1961, that disproved the notion that vertebrate cells can divide just just indefinitely, right?

0:44:07 Eric: Because logic there being once you run out of the ends of the chromosomes, right. No longer dealing with that protective cap on the chromosome. Now you're failing to reproduce actual genes that might matter. As you start losing the ends OF those chromosomes, there's a limit because eventually you're going to start damaging the important DNA. Right? Not only that, if you go below a critical length on those telomeres, your body will automatically shut down machinery. The good news is, as he describes all this, all of this has relevant citations, right? Is finally using the citation for this. Goes through several lines of evidence for establishing these limits to cell division, right, the fact that we have telomères that give us a cap to our aging in terms of cell division, he says, this possibility led to an experiment which yielded equivocal results. Results, a strain of laboratory mice with two disabled copies of a gene necessary for telomerase activity was produced. And These then what he found was that the telomerose negative mice, the that didn't have those protective caps, did have accelerated aging, but only after six generations. So only after they had six generations of mice. So I get what he means by saying that's not a super strong result.

0:45:11 Thomas: Wait sorry did he literally do this experiment?

0:45:13 Eric: He did not do this experiment. Is another cited experiment. The reason why it's equivocal is what he's saying is it's not the mice with the shortened telomeres that were initially edited, right? That were initially mutated that showed the increased aging. It wasn't even their kids, their grandkids, their great grandkids. It only started showing up after breeding that gene in over many, many generations.

0:45:14 Thomas: And why would I don't understand the sixth generation thing actually why would that be the the case huh

0:45:41 Eric: It also suggested a possibly limited role. Now, he could have followed this up with a series of experiments, right? Like, I could imagine putting back in telomerase in that sixth generation mouse, right, showing that maybe something else has been mutated in these mice as they start having altered cell division that might be responsible in the sixth generation, right. There are things you can do to validate observations experimentally in mice, right。 did not do that. Instead, he just went straight to kind theorizing about why these mice are different and why cancer appears in lab mice so often, reason why being that these mice Are often kept right pristine environment. So the thing that's going to kill them is not going to be things that normally kill these mice in the wild. But if you keep them going over and over again, eventually, they'll develop tumors because their cells are dividing. So it's going to be the cancer because there's not going to be a hawk that kills them. They're not going to get a disease in a pristine room, right? Not going to get scratched by some other mouse because you separate them when they're aggressive. That's kind of what he's saying is that a prediction that these mice are more prone to cancer, right. More importantly, that they would have more of these reserve capacity. And what he means by that is because they're not healing as much because they are not repairing tissue as much. They should have more cells in reserve that will actually make the cancer, even though they're not of that initially, it'll make the counter take longer to take root because they have all these other cells to out -compete the cancer and repair the tissue if it gets damaged, he's trying to argue is that it only becomes a problem when you don't have these other cells to kind of repair tissue and counteract the cancer cells. But that comes in balance with the more you have these reserve capacities, right? More you've used these reserve capacities, the more cell divisions you've done, so the more you've courted cancer, right. You can either get increased aging by not repairing tissue, or you can court cancer by repairing the tissue and dividing the cell. That make sense?

0:45:40 Thomas: Uh sure if you say so it's

0:47:37 Eric: He then has a prediction. Predict that proto tumors produced early in life carry you're proportionally higher risk of becoming mature tumors than proto tumors generated later in life. Is such a good experiment to do, right? You can track in mice when you inject tumors into them or when they arise, can then chart when they become mature tumors, when they start developing those mature markers. You also don't even have to use inbred mice for this experiment. You Can order outbred lab mice, ones that wouldn't have these problems that, um, don't match animals in the wild, right? Point being is you could set up an experiment that tests that prediction, whether proto tumors that are produced early in life, carry a higher risk of becoming more mature tumors. Is zero data that shows that he did that experiment. There is zero follow up. And this is my increasing frustrated as I go through this thesis. Every time he sets up one of these predictions or sets up a clear kind of model of what should be happening, there's never a follow -up that then validates or tests that model. And that's the part that's missing when we're doing science. That's the key thing that makes a thesis a scientific endeavor is that test, is that modeling, right? It's not the generation of a hypothesis that makes science, although that is an important part, it's how do I design the right test to validate that hypothesis or model? And that is just missing from this chapter, factor

0:48:57 Thomas: So but at the same time weren't you saying this is like his groundbreaking paper but

0:49:02 Eric: And that's why I'm so confused. It is like when I go on like our intellectual dark web and people are talking about brett weinstein right

0:49:04 Thomas: Who says it's groundbreaking then? Who says it yeah That's what I'm wondering. Like, is it a difference between like saying, oh yeah, this is so brilliant, here's what he did, versus, I mean, you could check the like the impact factor and all that stuff, right?

0:49:21 Eric: It definitely is that I want to be clear this is not like he does not have a claim to fame in the actual biology field right he even then says right we propose that uncompensated loss of some cellular lineages lineages coupled with the replacement of other lineages by neighbors diminishes the optimal ranges of cell types, both of which will diminish an organism's efficiency at accomplishing whatever task, um, cell differentiation initially evolved to address, right? So again, he's making a prediction that as these cells use up their reserves, right, as they start repairing more and more tissues, that tissue repair is going to get less and less, um less and less good. And it's going to have to use cells that don't belong to that tissue. Is a perfect opportunity to start using histology markers, right? To see if you're seeing cells from other tissues invading into other tissues in mice that you are breeding that are repairing things early on in life and then repairing things later on in Life, right. There are ways that you can track this stuff and prove it. He neither cites an experiment that does that or does the experiment himself.

0:49:28 Thomas: Thank God. Okay. Right. Huh.

0:50:23 Eric: And that's what I continuously get frustrated by. Are really good ideas in here, but it's hard to even make sense of those ideas without the model and the experiment that's being designed, want to point out, we are now 31 pages in. Have not seen a single figure, a single picture, a single graph, a simple table of any of the stuff that he has mentioned so far.

0:50:44 Eric: And that to me is wild. This point, if you were talking about things, you should be showing that clumsy evolution of flight and bats, right? Or showing your model of design trade -offs and how certain things do not exist at the same time. The math involved in your probabilistic trade -off, right. At At this point, you should be marshalling things that actually demonstrate your models and your points. And those are just absent.

0:51:09 Thomas: But thing we faced with the Jordan Peterson master's thesis is like, shouldn't his advisor have said something? So, shouldn't Jordan Peterson have said something? And back when he was allegedly a good scientist, and similarly, I don't know, like, shouldn't someone have said this? Like, I guess my line of thinking is, is this really a problem if someone signed off on it or something else going on?

0:51:32 Eric: And that's where I want to be very clear. Like, it is entirely possible that this is normal for non -molecular work. But again, I do want to bring up the main point that if this is normally for non molecular work, what he should not be talking about is vaccines and COVID. Right. So either way, it doesn't work the way it's supposed to work.

0:51:50 Eric: But I don't think it is normal, because I actually looked at Heather's thesis, right? Heather Hying, who was also at University of Michigan, has his thesis advisor as a committee member, and her thesis is titled, just very quick tangent, thesis istitled, The Evolutionary Ecology and Sexual Selection of a Madagascaran Poison Frog. That is a very specific. Exactly. And when I look at her list of figures, there are some 20 odd figures that are in this thing and ones that actually use experimental data.

0:52:12 Thomas: Hyper specific, baby. Yeah. So is she in a different field or subdiscipline or anything?

0:52:30 Eric: And possible. But I think what this is, is Brett Weinstein continuously coming up to the cusp of experiment and then removing his toes from the pool. And it will become more clear as we get to the end of this. Right. So then he goes through a section where he reinterprets, experimental um, results from previous literature. Again, that's fine. But if you're doing that at the end, you should have a new proposal, right? New experiment that you can do that will fill in those gaps, right. Or that will get at the actual thing that you think is happening. It's not enough in science to just say, I think this is wrong and we should think about it this way, do the experiment that thinks about it this instead of that way. Show the data. Show why it increases your explanatory power. Should be common among all fields. You should have something that is your own original work. It doesn't have to look like an experiment. For instance, let's go back to that evolution of bats. I'm not saying that he has to go into the lab and show the molecular mechanisms that's driving bat batwing evolution, but you should be able to go. I predict that the batwing would have started off very clunky and this type of shape. And then over the fossil record, you would expect either a movement in this direction towards more longer, elegant shapes, a movement towards even more sturdier and robust or a movement towards an intermediate phenotype. And then show that in the fossil records, that is a perfectly valid way of doing science that doesn't necessarily involve involve like a wet lab experiment.

0:53:58 Thomas: Bunch of bats. Yeah.

0:53:59 Eric: Still making a prediction. You're using data that, um, are collecting and you're analyzing it, right? Is still a kind of gross overview of the scientific method, but that's not what he's doing here. What he'sdoing here is he's reinterpreting other people's experiments, but then not using that as a springboard to his own experiments. And that makes it read more like a literature review than it does an actual thesis, right. Keeps going. Right. Talks about one really good prediction. I'll give an example. He He says, I would expect that larger animals. Right. Enter quiescent more quickly or will enter that aging process more slowly because they need more cells to build larger tissues and that they will have an increased rate of cancer because they are active for longer. Longer and because they have more cells that are possible to develop cancer, a great example of what I'm talking about, here would be a great example to put in a table, right. Show me animals gated by lifespan, the rates of cancer and all that.

0:54:32 Thomas: What's that? Hmm.

0:54:56 Eric: But not only that, exactly validate it in an out, out group, right, validate it into a data set that you didn't use to come up with your initial idea and then validate that it still has predictive power using that other data set. You don't necessarily need to generate new data, but when you're collecting that data, you have a prediction of what you think that data will be shaped by, That is a way where like you don't need to do a wet lab experiment, but you are still doing science.

0:54:51 Thomas: Yeah, couldn't Right. See if the mathematically lines up to something. Mm hmm. He didn't do that. He just predicted it.

0:55:24 Eric: There is none of that here. Just predicted. There's no table, right, there is no figures, there's no accounting for different tissues in the mice, right? He has another prediction. He would predict that the reserve capacity, right, the rates of cancer and stuff would be different in different tissues because those different tissues have different rates of cell division. He doesn't do any follow -up there, right. You have mice in your lab. You can look at histology samples. You can do actual things that match your predictions, right doesn t. He then goes from the the lab mice straight to clone sheep and talking about the history of clone sheep and whether they show premature aging or not, right? A little bit of a tangent, but again, his main point being that all of these lab animals don't have the same insults to their systems that wild animals

0:55:27 Thomas: Weird. Yeah? Right.

0:56:09 Eric: Do, so their aging is thrown off. Doesn't do any comparisons to wild type sheep. There are no, again, like it's just light on the types of analysis you would expect in science. He then says, we predicted that long telomeres observed in laboratory mice would be atypical for mice in general. Another great prediction, right?

0:56:27 Thomas: This in that master's thesis that sucked from the Jordan Peterson person, there was a section like this. And then, OK, here's our experiment. Did our predictions hold up?

0:56:37 Eric: That's what I'm saying. This is what's giving me whiplash, is I keep missing that. Even says, right, lab, who I'm assuming is a collaborator, Tested right. This with a survey of telomere lengths in six laboratory species of mice with short histories of captivity. Six had telomère lengths, approximately one -tenth of those in common lab mice. He's saying is that this is holding up. Would be a great place to put in a table of those telomere lengths and the different lab strains that were analyzed, but there is no table here.

0:57:04 Eric: Furthermore, I probably would have thrown in some outbred non -captive mice and see what the difference is there just as another layer of control. We have argued that laboratory mice should overwhelmingly die of tumors. Restriction, so altering the diet, may increase longevity in these animals by reducing the risk of tumor formation. Caloric restricted animals are approximately one -third smaller and exhibit slower cell replication than controls. By stunting growth and by reducing the rate of cell division, CR may simply reduce the likelihood of tumorigenesis. Such positive effects may also occur in those restricted vertebrates with wild -type telomeres. You know what that describes perfectly?

0:57:04 Thomas: An experiment.

0:57:46 Eric: An experiment that you can do. You what he did not do? Perfectly good experiment,

0:57:48 Thomas: An mean, And I'm not a scientist in science. Do you have people are like, nah, I'm more of a, I're more of a hypothesis guy. I don't really, you yeah, yeah,

0:57:59 Eric: I be honest? I think I would have been great at that role. Unfortunately, right? Just like I had to fail through my experiment for six years, at some point you have to actually do the experiment, right.

0:58:09 Thomas: A question I have. Why is Heather going down this shit with him then if she was able to do a thesis that was reasonable and had experiments?

0:58:18 Eric: I don't understand.

0:58:19 Thomas: Yeah. Who knows?

0:58:21 Eric: Point is, there are some good thoughts here, right? There are some really good thoughts here. All they need is actual science behind it. And when I say actual science, I just mean cited literature, designed experiments, data being analyzed. This to me just reads more like a pop science book I would get at Barnes and Noble. And again, there's nothing wrong with that, but it's just not a thesis, now we're at the conclusion of his chapter, this groundbreaking paper that that I've been told, right? He ends it by saying, finally, we are intrigued by the implications of the reserve capacity hypothesis for that correlation between body size and longevity. Because cell size does not increase with body size, effective tumor protection requires small vertebrates to arrest runaway growths at a smaller absolute number of cells. Therefore, the capacity must be low. This leads us to predict that birds, bats, and other vertebrate disproportionately long -lived for their size will also be disproportionately burdened by larger proto tumors and more frequent tumors. Again, what is the easy thing that he could do here? Could either do the experiment or look in data.

0:59:26 Thomas: Yeah, it seems very weird to, because like for all we know the experiment would just be like, oh, actually that didn't hold up. And then what is the value of just this, really. I don't know. Yeah.

0:59:37 Eric: The reason why I think this is important is because a lot of what he did in that Bill Maher video is a lot of, okay, speculation that sounds plausible, but doesn't hold up on cited experiments and doesn't consider, like, the reason why I brought up flu in that episode is because if I was designing the experiment that would disprove his nonsense about COVID being designed to spread indoors, I would look at other viruses and see their rate of transmission both indoors and outdoors, right? I think experimentally, I think of competing variables. I think alternative explanations. But if you're not doing those experiments, if you're not designing your controls, you're not training your brain to think of alternative models, to think of other explanations, to think of the pop, situations and conditions that you want to compare to. Right. I actually think this does speak to what we're seeing in that interview, because it's showing the same type of thinking that doesn't really conform to the more more scientific standard. Does that make sense?

1:00:04 Thomas: I also Also want to say that in general about this kind of thing, I think it's important to say I don't think it is as though you would use this example and then therefore say if anyone has a thesis like this, they are going to be a piece of shit too. It is more like the other way. I think people can be relatively young and writing theses that aren't good and then learn better and all that, but it is more looking at his behavior now and looking at like, OK, what were the signs?

1:01:01 Eric: Yes.

1:01:01 Thomas: It's more like from that perspective. And I don't want to put words in your mouth, but I just don't want people to think that we're like some framework for how you can always tell someone sucks or something. It's more the other way, like, oh, this was present here and is in retrospect a sign versus I'm sure there are plenty of people with bad theses who turn out to be perfectly fine and not arrogant pieces of shit spreading COVID misinformation.

1:01:25 Eric: Yes, absolutely. Most people, people's thesis are absolute garbage and most people try to run away from them and are like a shame to look at them once they've gotten more trained. The difference is most of them do have those standard things, right? That's not about quality. That's about a thesis should have experience.

1:01:41 Thomas: And And are there not any later published papers he's done that has that stuff?

1:01:47 Eric: So he has a grand total of four publications. I'm pretty sure we are looking at three of them in each of these three chapters.

1:01:50 Thomas: Come on. Oh, my God. How did he, have you checked out how the hell he got where he was? How did you get that job?

1:01:58 Eric: Got to be honest, this is where I lost myself on the rabbit trail because it just got so bizarre reading. We're now 56 pages into a 99 page thesis, and I've not seen one piece of data, one pieceof table, one figure, one model, right? That's wild to me. Should be doing things that show your work. Like, I get what you're saying, but honestly, it actually would give me pause if like, they did not have subsequent papers that showed that they've refined their scientific technique.

1:02:25 Thomas: No, that's more than just one data point for sure.

1:02:29 Eric: Like I absolutely agree with you. Most theses are terrible. Most of them aren't signs of who they will become. You are right that this is a reverse engineer, right? Where I, yeah, yes, yes.

1:02:37 Thomas: Wasn't claiming that most of them are terrible. I'm just saying there are plenty that are terrible that don't mean you're Brett Weinstein. That's all.

1:02:43 Eric: But this one is terrible in ways that are frankly weird and ways that show the type of stuff you're talking about, kind of ticks of the intellectual dark web, for lack of a better word. I would say the way it's written, the lack of kind of mechanical writing, like it, science sucks to read. It's very dry, it's very mechanical, you're constantly citing things. You're constantly referring to figures, results, and data, It right? Is very blocky and choppy to read science, right? This was actually pleasurable to read for for better or worse, right. We're going to go to chapter two. Chapter two is those design trade-offs between, do you want to be that generalist in times of scarcity? Or do you want to be a specialist in times of plenty? Right? And here he does have theoretical models. He has things that show what he's thinking and how different environments will affect kind of the selective landscape and then where you fall in that trade -off continuum. Are you an extreme in capacity A? Are you an extreme and trait B? Or are you somewhere in the middle? Right. What he doesn't do is bring that theoretical to the actual. So he talks a lot about this kind of gradient of biodiversity, where things are really diverse at the rainforest and then really not diverse in the poles, right? The reason for that, he would argue, is that in the rainforest, there's plenty of resources, right, so you don't have that selection towards generalists, you have that diversification towards specialized niches, right. Whereas in the poles you have um more generalist phenotype the first thing I would say is like this is stuff that biologists have thought about and in fact I'm pretty sure we discussed this on why birds survived the extinction in our last episode and that was before I read this thesis the second thing though is that even if you grant that this is like a novel idea and stuff don't test it in the observation that led you to make that model go to the fossil record we can track environments over time and rock samples, right? Can look at species diversity at different locations. You can make datas and correlations between the environmental repleteness for resources and the species biodiversity, right. Are ways that you can validate it, or here's one you could do in the lab, grow bacteria, have lots of different food sources in that dish for the bacteria, and then see how that diversity develops over

1:04:55 Eric: Time. There are experiments you can do to validate these ideas. He is just not doing them. Makes this even more frustrating is he says in two different parts, what the model predicts about tropical ecosystems, right? What the Model predicts about pole ecosystems, right? Terms of species diversity. Here's a great part to put a table. Show me species diversity in Olympia temperate rainforest, in the Amazon rainforest, and then show me species adversity in the Gobi Desert, in The Alaskan Boreal Forest, right. There are ways you can validate this idea using data that isn't just intellectual fluffing and hypothetical ideas. Ideas. Third one, I don't even know if we need to go too in depth because of time. Just want to point this out. Starts this chapter with this quote. Are not enemies, but friends. We must not be enemies. Though passion may have strained it, must not break our bonds of affection. The mystic cords of memory stretching from every battlefield and patriot grave to every living heart and heartstone all over this broad land will yet swell with the chorus of the union, when again touched as surely as they will be by the better angels of our nature

1:04:54 Thomas: Be cool yeah address or

1:06:02 Eric: Abraham lincoln second inaugural address again this is a awesome chapter header for a pop science book what

1:06:02 Thomas: Whatever yeah well literally the better angels of our nature that's a steven pinker book I assume assume you know what I'm yeah

1:06:15 Eric: It really just yeah but what it just isn't is what you put in a thesis okay

1:06:21 Thomas: I don't even understand the relevance yeah

1:06:23 Eric: The upshot of this one, Is right. That humans, um, two different competing interests. They have their individual interests and their group interests, and they choose their game theory of morality and whether they're going to adhere to it or not based on whether resources are scarce and they need to kind of collectively fight off outside groups and band together or whether resources Are replete and the competition within group is more important. Again, zero mechanisms. There's zero validation of data. You can find proxies for things, or at least try to find proxys for things. You want to look at crime rate based on a function of income. Maybe You want to Look at war as a function of potable water. Things that you can do that I would have more than 30 seconds to come up with, because I'm spending seven years on this thesis, that you can design that would actually show this, right? He doesn't. And it's all, again, about kind of using stuff like we propose that people vary in the relative importance they place on individual versus group in the working value systems or decision rules. A lot of statements go, we hypothesize, we propose. What they don't do, basically

1:07:29 Thomas: Who's me got a lab mouse mat in your pocket

1:07:38 Eric: Of this paper. I think this was co -authored with Laidi.

1:07:39 Thomas: Is is the call oh this is not his thesis oh

1:07:43 Eric: This is another one of those taking a paper and stapling it into his thesis. I point being, once again, what he's not doing is generating his own data. He's notdoing any of that. He says, we propose that the reason why cooperation does not automatically collapse or cycle in a way suggested by economic models is because such Such models have not yet taken into consideration the general tendency towards facultive adherence towards moral norms and the resulting negative feedback on booms and busts of cooperation. There is zero citation there.

1:08:12 Thomas: Also sounds like evo psych kind of

1:08:14 Eric: About to say, this is going to be more of a question for either Dr. Seymour or one of your more psych -oriented people, but there are experiments you could do would get at this question. There are survey questions that you can make that would getting at this questions. But he doesn't do any of that work, partly because he has now gone into a completely different field.

1:08:30 Thomas: Well how's it even related to anything he's done Yeah.

1:08:34 Eric: It's just such an overbroad topic. This is a thesis in itself. Trying to prove the evolutionary roots of game theory is just... a great example. One prediction from this hypothesis is that studies of moral judgments in social context will find perception of group stability to be a significant determinant of the outcome of moral deliberation. Is very easily something psychologists can design tests for, right? That is something you can, not easily because it's a complicated thing to design psych evaluations, but it's something you could do, right? He collaborate with psychologists to test this though? So we keep going, we keep Going. And again, there is just very little experiments and any data he brings is not his own. It is someone else's, but not even in ways that he's using in novel ways, right? You can use data from other labs, other papers, other experiments, and change the parameters of your analysis. Look at it from a different perspective. Include another data set to compare to. That would make the data set and the analysis your own. He does none of that at any point. I cannot stress enough how weird it is to me that we are now 99 pages and I haven't seen a experiment. Is the last paragraph of his thesis. These hypotheses deserve testing for at least three reasons. They explain why morality has an air of absolutism despite the facultative nature of human commitment to moral rules. Again, I would like him to show that human commitment of moral nature is capricious and based on certain things with some literature cited. They resolve the long -standing debate about the adaptive status of moral rules. And third, they connect moral attitudes to environmental variables. So he's making all of this case for why we should test these hypotheses. Is that not his thesis?

1:10:16 Thomas: Do you get awarded a Ph.D. for this? Yes.

1:10:20 Eric: Is, and I want to be as fair as possible, but this is my point of confusion. At any point in any of these chapters, did he actually do a test that generates new data that he has to analyze himself? Would say no. I don't mean this pejoratively, because I actually hate when people that kind of new atheism science area start kind of dumping on philosophy and the humanities because they have just as careful thinking, just as fearful stuff. This is a very good philosophy or psychology thesis in this last chapter. It just doesn't belong here, and it doesn't fit the way a science thesis is supposed to look.

1:10:43 Thomas: And most Importantly, again, like the point you keep making, it doesn't qualify him to make the claims he's making. Like, it's fine if this was in the privacy of his own bedroom if this is what he wants to write about and how he wants to do it, whatever, fine. Definitely doesn't seem to make him qualified to opine on COVID and vaccines the way he has.

1:11:17 Eric: Exactly. And you'll actually notice, is I did very little commentary on his analysis of the evolution, right? Didn't really talk about whether I agree with a lot of what he's saying in terms of senescence and proliferation, right. I didn'T really try to push back, because I recognize this isn'T really my field. All I can really comment on, am I seeing things that look familiar to me, look like science, right, that you can analyze regardless of the field, because regardless regardless of what he's doing, there should be things that look like science. The way that Heser's thesis dealt with a very narrowly constrained topic and does experiments and analyzes data sets that she collects. Should be independent of field, you're writing a philosophy paper. If you're reading a philosophy paper, it's not that it's less rigorous, it is that it does different things. And I haven't read a lot of those. But to me, this reads more like a philosophy paper, and that it's dealing with a lot of hypotheticals, a lot of, if this were true, we would expect this, but never actually does the work to organize it and test it, right?

1:12:16 Thomas: And actually to drive further the point home, correct me if I'm wrong, there's nothing wrong with philosophy. I love philosophy. If this were the qualifications that one had, you could attempt to critique something like maybe COVID or COVID vaccines, but at I feel like you could only do it in a similar way where you could say, hey, I have these conceptual conceptual concerns and let's test it in the same way you could you could hypothesize about it and then people who actually do experiments and know the science better could be like oh as you have already you know kind of outlined in the previous episode oh no with that concern doesn't make sense we already knew this and then he'd have to sit the fuck down you know you can't be like both the person who only has a history of you interesting questions for other experimenters to answer and then simultaneously do that and also be the like end arbiter of all scientific information about covid uh you have no experience on that second part yeah

1:13:11 Eric: Exactly. And what you definitely shouldn't do is say, I'm 95% certain that this was created or that this Was leaked from a lab, right. Then just one final point about all this, because me try and think about how I want to phrases.

1:13:18 Thomas: Brett Weinstein fucking sucks final point yeah

1:13:28 Eric: It's that a lot of the things that I'm seeing in terms of the lack of carefulness, the privileging of proposed models that have grand theories of explanations instead of grappling with the data and the models as they exist in reality, has its seeds in this thesis, right? He talks about like, well, you would expect this of a vaccine and this of that, these are answerable questions if you have the ability to look at how the mechanism of the vaccine works, if you Have experience pouring over data of those clinical trials, what he doesn't have his experience in analyzing that type of data in looking over molecular mechanisms. And that leaves him poorly equipped to make the types of judgment calls that he's doing in the same way that I don't make the claim that I know why sugar gives energy the way that it does. I don't study metabolism. I don't know the types of assays that we do that process that sugar and that metabolism. I can talk about vaccines because I've done research on viruses, because I have used the type of experiments that vaccine research does. That doesn't mean that I know everything thing about biology. What Brett Weinstein does continuously is take a very limited, well, not scope, but a very Limited toolkit from his thesis, and broadly apply it to feel that he has no business applying that toolkit. And that's my main point is that even if this is a perfectly good thesis for his subfield, what it's saying is that his sub field should not be talking about

1:14:57 Eric: COVID.

1:14:57 Thomas: But I feel like you're also saying you suspect though you wouldn't say you're 95% certain, I suppose, you suspect this This isn't even a good thesis for a subfield.

1:15:08 Eric: And I would say not even a good thesis misses the point that I suspect. My thesis was not a good basis. Suspect that this doesn't even have the structure of a thesis in any other student's work in that subfield. Wasn't able to find another one. What I really tried to do was find a thesis from Richard Alexander's lab and compare it, thinking that if they're in similar labs, you would expect similar structures to their thesis. I was unable able to find that. But I cannot stress just how weird it is that every chapter ends with a proposal and not an experiment and results. Results are what your thesis is supposed to be. You have done the experiments. You are now analyzing them. All I got. Right.

1:15:48 Thomas: Well, this was a really fascinating deep dive. I what I was worried about when you were kind of, you know, hinting at the outline of this a little bit was, oh, well, but is it going to be like, ah, his thesis sucked? And then, you Know, the obvious counter would be, yeah. But OK, look at all his later work that is actually good. And it just really seems like that's not true.

1:16:07 Eric: Was actually re-looking over his thesis today. And because I'm a masochist, I was also on the subreddit for the intellectual dark web. Right. It turns out that Jerry Coyne, who's another kind of biologist that's written a number of pop science books, he does. But what he did say was after hearing some of Brett Weinstein's arguments about evolution, I can no longer take him seriously as a biologist or an intellectual. And I just came across that today. Yeah. So but it had to do with like evolutionary mechanisms. And this is actually more in Brett's wheelhouse, right?

1:16:19 Thomas: My god Jerry Coyne fucking sucks Jesus

1:16:39 Eric: It would be more. Oh, What Jerry Coyne said was that the large kind of structure of biology, his evolutionary theory has already been solved, right between Darwin, between neosynthesis of Darwinian evolution.

1:16:33 Thomas: What yeah oh I think I remember this actually I think I might have come across this and it's like ah two people I hate are fighting and what do I I how do I feel about this of

1:16:58 Eric: What it's worth in this particular argument. I'm team Jerry. Most of science is not going to be paradigm shifting. It's going to be those margins.

1:17:01 Thomas: Course yeah yeah I my impression would have been having interacted slightly with Jerry uh Coyne is that I'm sure it like it wouldn't surprise me if you were to do another thing and like he's full of shit but I've never got the sense that he was totally bullshitting about his subfield I just he's just a reactionary piece of shit asshole that I've had a decade of unpleasant kind of like uh with well okay I stopped interacting with him a long time ago but I've I've witnessed what a miserable you know anti-woke piece of that guy can be online but I to lend credibility to this it's not as though I would go around thinking everyone who is like that also happens to be a fraud in their field and is not whatever you know like I think it it's

1:17:43 Eric: I am pretty sure he is a perfectly cromulent scientist that has a very productive paper record, right?

1:17:47 Thomas: That's a better way to put

1:17:48 Eric: That would dwarf mine, right?

1:17:48 Thomas: It yeah yeah exactly exactly he

1:17:51 Eric: Would absolutely trust his publications. I would trust his experiments. I can't even trust Brett Weinstein's experiments in publications because they exact, like, this is the part that I just cannot stress enough.

1:17:59 Thomas: Doesn't have him but but make sure to finish the uh the thing that I interrupted you can you finish telling what the Jerry Coyne thing was yeah

1:18:08 Eric: So basically he said, I no longer respect you as a intellectual because what Brett Weinstein was saying was that we have the broad strokes of evolutionary theory solved, and we still have major, major gaps. I would actually say that's ties into what we were discussing at the very start of his thesis. Narrow theses that I would write, that Heather wrote, grapple with the idea that we're just coming up with stuff on the margins, right. Thesis that Brett Weinstein wrote is one that aims to shift paradigms completely. A broad, let's start thinking of trade -offs as the organizing principle of evolutionary theory. Does not circumspect, it is not coming at the margins, it is trying to overturn large parts of evolutionary theory.

1:18:46 Thomas: This guy oh boy I love it when even even the fellow fellow dork web assholes are like, oh boy, I can't quite go with that.

1:18:56 Eric: An important part for me because I am not generally narcissistic and arrogant, right? My mind, I'm seeing a published thesis. I'm seeing what I think of as nonsense. And it's nice to hear another credible scientist echo some of those similar thoughts that, because at first it's kind of the emperor with no clothes, right. And I, I think I'm seeing something

1:19:15 Thomas: No, it's a very It's a very healthy thing to be like, I must be missing something first, you know, but it's also important to, when you have someone like Brett Weinstein spreading very dangerous, harmful information that's likely responsible for loss of life. You know, like, honestly, he's an influential voice. It is It's important that the use of the world do need to go ahead and put yourself out there a little bit because not, maybe the good scientists aren't doing that enough. You know, like they aren't coming out and saying, OK, I don't want to sound arrogant, but that guy fucking sucks.

1:19:45 Eric: And the irony is I was a bad scientist, but yes, that was, that was the motivation, right in general, what I would much Much more rather do is talk about CRISPR, talk about the day the dinosaurs died, do that really love of science, basic stuff. When you have this guy that really shouldn't be talking about COVID, spreading harmful misinformation, I think it's important to kind of set the record on what his credentials are, where his perspectives are, and whether he is a trusted source.

1:20:13 Thomas: Absolutely. Well, thanks for that thorough deep dive. Perhaps we'll cover Brett a little more on on where there's woke or the something future, because I think having firmly established that this guy does not have the kind of, you know, I guess maybe not credentials, but like the what would you say? A yeah

1:20:31 Eric: Demonstrated skills is what I would say. So

1:20:33 Thomas: Like is perhaps his perch from which he has sat is not as uh deserved as maybe we thought um be interesting to go through more of his bullshit and that knowledge kind so much of it I mean there's endless bullshit and I've really appreciated your debunking of it so right. Well, I want to thank you again so much for coming on, Dr. Eric Jaffe. Been a pleasure. It's always a pleasure and looking forward to next time. Hey, Hey, do experiments, kids. Don't just propose things.

1:21:00 Eric: For having me and hopefully next time we'll actually be able to talk science instead of a lack of science

1:21:04 Thomas: Nice. Until then.