19: Bret Weinstein - The Prediction and the DISC: Difference between revisions

'''Eric:''' And then there are a few predictions. So, am I right? Darwin started this game off by predicting that there would be a moth with a really long tongue because there was a flower that had a really long distance to go before you could get the nectar out of it.  

'''Eric:''' Yeah, clade of orchids, the Ophrys system, which is just unbelievable because it mimics the pollinators, the female of the pollinator species using pheromones and some sort of replica good enough to fool males into copulating with the lower pedal of an orchid—

'''Eric:''' Right. So Darwin saw that there was this mimicry going on, but he couldn't put it together. He spent pages and pages not getting it. So I think it's very funny. So he predicts some things, but he can't predict something else in a very closely related system. Okay. Fast forward, Dick Alexander comes out with a crazy prediction, which I still don't fully— I mean, it's just amazing that he made it— where he says, I bet that you will find the kind of behavior we associate with wasps and bees, which is in this clay called hymenopteran ants of eusocial breeding patterns and organization, but in mammals that will live underground.  

'''Eric:''' So we should say that there's something funny about the system of ants, bees, wasps, which is that they've got this very strange haplodiploid chromosomal characteristic. Do you want to say a word about that? Cause that makes the prediction more—

'''Bret:''' Sure. So it has long been understood that the hymenoptera behave in this incredibly cooperative fashion, which effectively all of the workers of the colony forgo reproduction in order to advance the reproductive interests of the queen. And it was late discovered that actually their genetic system is unlike our genetic system, and that males have basically half a full complement of genes. They have enough greens to function, but they have half the female complement of genes. And, for reasons that are mathematically slightly complicated and require a chalkboard, the females are more closely related to the daughters produced by their mother than they would be to their own offspring, their three quarters relatives to her offspring. And there they would be 50% relatives to their own offspring.  

'''Bret:''' Yeah, underground, I believe eating tubers, was on the thing. It was a crazy list. And you know, my understanding from, from Dick—Dick is now unfortunately dead. He died a couple of years ago. But my understanding from him was that he didn't actually expect to find such an animal. He was speaking very abstractly, just completely theoretically. And at the point that he unleashed this idea, it may even have been in a talk, rather than a paper. The information made it back to him, actually—what about naked mole rats? They match your characteristics, and study reveals then that actually they are eusocial, they behave very much like ants, bees, wasps, termites, et cetera.  

'''Bret:''' Evolutionary biology has long been biased in the direction of abstraction. Rather than thinking about mechanism, that is to say we deal in the phenomenology of things. We talk about gross patterns that we see in nature rather than talking about the fine detail of what drives them. That has been changing in recent decades, but it has a long history, and it comes from a very mundane place. That mundane place is that we just haven't had the tools to look, for example, inside of cells and we haven't been able to read genomes. You know, we could have been able to read a gene here and there at great expense, but the ability to peer into genomes is pretty new. The ability to peer into these molecular pathways is pretty new. So anyway, there's a historical bias in evolutionary biology against mechanism and in the direction of phenomenology. I have never been particularly fond of that bias. I have always been interested in mechanism. I'm interested in the phenomenology too, but I've always kept my foot in the door with respect to mechanism. And as an undergraduate, I took lots of mechanism classes. I took a development class at the time, developmental biology was in my opinion, a bit stuck. It is now unstuck in a very dramatic way. But anyway, I took a developmental biology class. I took some or immunobiology. And anyway, I was armed with these things in an environment in evolutionary biology where most people were not, most people were in the phenomenology. And one day I happened to be in a seminar. Dick Alexander was running a seminar for graduate students, and a student was there who was very out of place. He was studying cancer, and he, on a lark, decided to take an evolution seminar that looked good to him in the catalog, and it wasn't right for him. And he gave a talk at some point, and his talk was on his work with cancer and frankly, because all the other people in the room were evolutionarily oriented, nobody was really tracking what he was saying. But what he said struck me like a bolt of lightning. He said that in the realm of cancer research, people were looking at telomeres, which are these repetitive sequences at the ends of chromosomes. And they were toying with the possibility that the fact that these telomeres shorten every time a cell divides, that that is providing a resistance to tumor formation. Very straightforward—counter counts down, and that would prevent—

'''Bret:''' Yup. It was the discovery of Leonard Hayflick, who basically overturned the prior wisdom about cells, which was that they would grow indefinitely as long as you kept feeding them and making an environment that was conducive to division. So I don't exactly know why that result had been misunderstood at first. Maybe somebody had a cancerous cell line and so they got the wrong idea and it just spread, but Hayflick checked it and it turned out to be false. It turned out there was a number of cell divisions that healthy cells would go through, and then they'd stop. The mechanism was not obvious to Hayflick, but later it became clearer and clearer that the mechanism was these sequences at the ends of chromosomes which shorten each time the cell divides. And the implication was that, potentially, this was a cause of what we call “senescence”. What in common parlance would often be called “aging”, the tendency to grow feeble and inefficient with age. If your cells are each in a cell line and that line has a fixed number of times that it can replace itself before it has to stop, then some point your repair program starts to fail. And that repair program, failing across the body, looks like what you would expect aging—aging follows the pattern you would expect if cell lines one-by-one stopped being able to replace themselves. So—  

'''Eric:''' We know that there's a special sort of a, I don't want to call it cell line cause you keep correcting me for every tiny mistake I make in speech. But, if we divide our body into two kinds of cells, soma and germ, where germ lines are that which has a hope of immortality through reproduction, then it's the somatic cells that have finite limits on their ability to undergo mitosis and cellular repair and whatnot.

'''Bret:''' And the germline can't because if it did, your lineage would go extinct as a result of small—  

'''Bret:''' So it's the soma, the parts of your body that don't go on to produce babies, that have this effect. The reason it struck me like a bolt of lightning was that I was aware of another very elegant piece of research done by a guy named George Williams. George Williams had finally—

'''Bret:''' One of the greatest modern evolutionary biologists. I actually knew him a bit too. He is also now gone, unfortunately. But George Williams had laid out in a beautifully elegant paper, the evolutionary theory of senescence. It is an absolutely elegant argument that says that, in a lifetime there are, well, let's start somewhere else. A creature is built of parts and traits. It has a relatively small genome and a relatively high complexity. At the time it was thought there might be 100,000 genes or something and you have maybe 30 trillion cells with a ton of complexity. In order to get that small number of genes to dictate how to produce a creature that complex, the genes are doing multiple things.  

William's point was when a gene has multiple effects, what we call a pleiotropy, those effects may be good or bad. If effects are good early in life—  

'''Eric:''' The hypothesis is the Antagonistic Pleiotropy Hypothesis.

'''Bret:''' Right. So I began to focus on this question and I did something that was the right thing to do, but I did it in a way I will forever regret. I found somebody who was represented in the literature, who I regarded as very well versed. They made sense to me, their papers. Her name was [https://en.wikipedia.org/wiki/Carol_W._Greider Carol Greider]. Carol Greider is now a Nobel Laureate. She was not at the time. She was the co-discoverer of the enzyme telomerase, which is the enzyme that elongates telomeres, when that occurs—

'''Bret:''' Oh, I sure can. Vioxx, for example. So Vioxx was discovered to do heart damage, right? Heart damage. How do you, why do we know that it's heart damage? Well, the thing about hearts, for reasons we can get into maybe another time, hearts have a very low capacity for self-repair, right? That's why they're vulnerable to heart attack.

'''Eric:''' This isn’t the only system that doesn't have a lot of mytosis, like for example, neurons.