 scrolling. Hello, everyone, and welcome to a live broadcast of a special twist broadcast. We are joining you at an odd time. We're normally here in the evenings, but I am so excited to be joining you on a Wednesday in the morning here in the Pacific Northwest. Some of you may be afternoon, but I'd love to just get started here. This is This Week in Science. We're recording a special interview on Wednesday, October 20th, 2021 with Dr. Neil Shubin. Happy, happy day of science and Dr. Shubin. Thank you for joining me today on This Week in Science. My pleasure. Happy Wednesday. Happy Wednesday. It's a good sciencey Wednesday. It's the middle of the week. We got to keep things going. Keep people's spirits up with science. Give them something to get them through the week with science. You got to do that. Absolutely got to keep going. So you are a professor of evolution. You have written several books. You discovered Tectolic, one of the, I don't know, people consider it one of the most important transitional fossils, discovering that transition between water and land living animals in the fossil record. And now you've come out with another book, Some Assembly Required, which investigates four billion years of life from ancient fossils to DNA. And I just want to know about your evolution from digging up fossils and looking at their physical form to this new stage of looking at and considering the DNA and how that has, how that transition through your career has happened and how it's influenced your thinking. Yeah. So the book, Some Assembly Required, was truly a labor of love because it not only talks about evolution, which I adore, but it talks about my own evolution as a scientist in some sense, because, you know, I went to graduate school to train as a paleontologist, learning the toolkit of paleontology, finding creatures like Tectolic Rosia, which is an intermediate between life and water and life on land. There's a toolkit and there's a, you know, there's a rule book and a playbook that paleontologists have used for over a century to find these things. You know, and I was training to do that. And I remember when I was in graduate school, I saw a single slide that launched my career. It was like, here's the fish to land living animal transition, fish to tetrapod transition, fish on top, tetrapod on the bottom. I'm like, what's in the middle there? You know, so that became my quest for a number of years. So while I was training to be a paleontologist, I was out in a field expedition once, and I came back, this is like in 1987, maybe something like that, came back to the office and a fellow graduate student laid a bunch of papers from molecular biology, DNA technology on my desk. And it blew my mind. And I realized, oh man, I either have to change or die. Don't become a fossil yourself. Is that the? Yeah, like one of my fun. And so what these papers were is it showed in flies that there are certain genes that build the body of flies that place the organs in the right position, like in, you know, the antenna and the head, the legs, you know, the body and so forth. But that was cool, you know, that there are certain genes that control the architecture of the body of flies was great. But what was really powerful was that versions of these same genes these papers showed are present in fish, frogs, mice, and people. That is that there's a common toolkit to build the bodies as different creatures as different as worms, flies, fish, frogs and people. So I'm looking at this thing, I'm saying, okay, I'm trained to be a paleontologist. That's great. I'm still no paleontologist, but I'm going to need this other toolkit. I'm going to need to learn this molecular stuff and real fast, because it's very clear that what's being uncovered are sort of understandings of the genetic basis by which bodies are built. And once you know that, I can compare the bodybuilding recipe of a fish to the bodybuilding recipe of a amphibian, to a mammal, to you know, to mammals like humans. And, and this was in the late 80s. And I realized I had to train so I had to learn a whole new field. And yeah, so it's been great. I haven't looked back, you know, so ever since I have a lab, it's like right here, I'm in my lab. It's split brain. You know, we have a fossil area where we're working on new fossils all the time, leading expeditions. But there's also a very big molecular piece where we're looking at the DNA of living creatures, and ask the question, can we uncover how they develop and the genes involved in their development, and then look at them in a comparative way. And the technology has just exploded. I mean, we're doing things in the lab now, I couldn't even dream about 15 years ago. You know, that's the kind of thing it's like living in different worlds, you know. But it's so powerful, right? I mean, it's just exciting. Yeah. But how is that, that split brainedness? And when you go about thinking about studying something that you're digging up in the field, and then kind of comparing these genetic aspects and looking at various things, how did? Well, sometimes it's invigorating. Sometimes it can be driving crazy, right? I mean, it's like anything. I mean, it just depends. So, like, you know, I might be in Antarctica for two, three months, and then come back to the molecular lab, and it can be a pretty jarring transition. But what's interesting, and where this really works well, is that DNA technology comparisons of DNA and development and embryos are going after the same questions that I'm after with the expeditions and paleontology. That is, it's all at the service of answering the question, how do the great transitions in evolution happen? One way to approach that is find the intermediate fossils, like tiktolikrosia and countless others, right? But the other is to use these techniques to that. So it's really kind of a question and a scientific problem that brings these different strands of research together. So in that sense, it's really invigorating, because one informs the other. And look, now there are times when it will truly drive me crazy when the wheels fall off the cart, you know, when experiments don't work, or when I'm struggling in the field, or you know, you're in two very different scientific cultures, you know, the fossil finding culture versus the molecular biology culture. But those, fortunately, those times are relatively rare. And honestly, you know, the reason why I went on into science was to continually learn, right? And this is kind of keeping me, keeping me at it, you know, keeping me honest, keeping me learning. Allowing you to continue to learn, keep asking new questions and discover new things. That's why we do this stuff, yeah. I hope so. I mean, you kind of hope that scientists are liking to ask questions. I'm thinking if they don't like to ask questions, they're in the wrong field, they should be so cute or something. If you don't want to solve problems, if you don't want to creatively come up, come against how to find new information and learn new techniques, and that's right. That's right. Yeah. I mean, that all goes with it. So and, you know, and I find myself continually sort of changing the questions I'm asking to as I learn about more about these techniques. So we ask a lot about how genomes evolve, you know, and how gene functions, how the functions of similar genes and fish and people evolve. And it kind of changes how I look at paleontology as well. That is, you know, sometimes I'll realize there are gaps in the fossil record. I wouldn't have seen if I didn't think about the molecular piece in vice versa, you know, so they really do feed different parts of my personality, but also more importantly, they really work together to sort of solve problems and give us new insights which we couldn't have envisioned before. Otherwise. Yeah. From the, you know, historically, before we had the ability to investigate the genome, we were strictly going off of relationships based on structure, morphology. So we know that this animal has certain teeth ridges in, you know, the three, three ridges on the molars versus four ridges on the molars and this trust me, I trained on that for five years. I knew every little bump on every little molar. Exactly. So for this relationship and, you know, the entire family tree of birds we have inferred from plumage and beak shape. And we know from scientists like Darwin that beak shape from the finches is quite adaptable and can change very quickly. So how much has evolutionary biology, paleontology changed and been affected by now being able to really learn these relationships more specifically because of the genetic information? Yeah. So, I mean, one of the things is, and I got to say, is paleontology itself has undergone a revolution even without my molecular biology in the last 15 years. There's a couple of things that really changed it. Fossil hunters have gotten a lot better at their jobs. They can really can now know the geology and the conditions a whole lot better. So when you look at like fossils like Tectolic, which tell us about evolutionary transitions, that's just the tip of the iceberg. There are whales with legs, there are dinosaurs with feathers, there are all kinds of new hominids discovered every couple years. And so that's, and that's changed a lot because technology as well, CT scanning technology has evolved to the point where we can scan inside rocks. But the one of the things that we see with molecular biology is something that we also see with paleontology. It's kind of interesting. We see the same pattern in genes as we see in fossils is that the notion is that the great inventions that allow the big revolutions in the history of life like lungs and the invasion of land or feathers in the origin of flight, all these things came about before the revolution. So if you think that, you know, lungs arose to help creatures live on land or feathers arose to help creatures fly, you'd be in a really good company, but you'd be entirely wrong. We know that now that lungs arose eons before fish ever took the first steps on land in fish living in water in that had depleted oxygen. So they had, it was like an accessory organ, you know, likewise feathers was, you know, for thermoregulation or courtship displays in dinosaurs before flight, you know. So a lot of evolution is using old structures in new ways. Well, guess what? We see that same pattern in genes. That is, we see the same toolkit that build versions of the same toolkit to build our bodies are seen in flies and fish. And so it's been repurposed as well, just like that. So, I mean, what you have is a common framework that's developing. And this is kind of what I discuss a lot in the book, you know, that allows us to integrate the discoveries based on genes and organs and fossils and stuff like that. So it's actually a really exciting time. It changes how I see the great revolutions in the history of life. No doubt the genetics does. Because, you know, you can think about it like, oh my goodness, you know, going from a fish to a land living animal, that's just took so many steps. Then when you look at the genetics of it, well, not so much because the genes that make our lungs, guess what? They're present in fish and what are they doing? They're making breathing organs. The genes that make our fingers and toes, guess what? They're present in fish and they make the terminal ends, they're fins. So what you're seeing is a deep continuity among creatures that you wouldn't really have expected otherwise. Yeah, one of my favorite studies that occurred, I think while I was in graduate school in the 90s, was researchers who stimulated, turned on the genes for teeth in chickens. So that being the idea, and there were researchers since then who have been like, maybe we can turn a chicken into a dinosaur. And it's like, well, a chick story. Yeah, I don't know. I mean, you could do it. It's just going to be a chicken store. That's what it'll be. Yeah, but it, you know, these kinds of relationships are, you know, knowing that there are, like you said, it's a toolkit. The genes are there, and the tools are there. But then there's a different level of control to decide how and when different tools are being used. That's right. And that's a key insight that you bring up. And when I talk about a lot, and it's been sort of part of the scientific discussion for at least two, three decades. And that is that, you know, you can use the same genes in different ways. That is, the same gene can be used in many different developmental processes. So you can have a gene that's involved in lungs, involved in genitals, involved in skeletons, involved in digestive organs and so forth. And basically what there are in the genome are a lot of control sequences, switches, regulatory sequences, which control the activity of genes in different places in different times. And the more we learn about genomes, the more we realize that only 2% of the genome are genes that code for proteins. That other than 98%, there's a lot of stuff. Some of that stuff are these control elements that regulate genes that are their switches that control where and when they're turned on and off. And it turns out that that's a major process of evolution. That is much of the evolution of new body plans, new organs and so forth, new functions. It doesn't really always involve a whole ton of new genes. It means you're using old genes in new ways, which is the same thing we see in the fossil record and other things. So that's the beauty of the whole thing. Yeah, I love that it's kind of, oh, we've already got this. The genes are like, I just got to stay in here. I'm going to find a way to stick around. But in the book, you talk a lot about jumping genes and you talk about the potential effects that can occur as a result of the jumping genes. And you speak a little bit about how some of these genes, these jumping elements are selfish genes. And I love that because it kind of goes back to the idea of the selfish gene in general, where the gene doesn't care about us. The gene cares about the gene and the genome is just reproducing itself. So is it just some genes are more selfish than others? Yeah, and some are better selfish or better at being selfish than other too. So really, when you think about it, you know, there's a battle going on in genomes. That is, there are certain elements that are there and they really all they do is make copies themselves throughout the genome and jump around, right? And there are different ways that happens. I've just reduced it a lot. But, you know, there's different ways that happens. But essentially, what happens is you have a gene that makes a copy of itself that lands in different parts of the genome. So if you look at our own genome, a huge fraction of our genome are repetitive sequences just one after another after another up to 60% maybe more of the selfish genes that there's a duplicate duplicate duplicate duplicate duplicate. Now, you can look at them as sort of a parasite in our genome and sometimes maybe that's a good way to look at it. But interestingly, what researchers have started to view in the last decade and a half or so is that sometimes these genes these jumping genes can carry a mutation across the entire genome. So sometimes we think you know if you have a mutation that appears in one place affecting one gene, fine, no big deal. Yeah, no big deal. Maybe a small change. But what if that's a tethered to a jumping gene, and then goes across the genome, all of a sudden you can you can have a single shift or a relatively small number of shifts that can bring about a large set of genes involved in an evolutionary change. And that's where it's particularly exciting. I think there's there are a number of cases where particularly like pregnancy and things like that, where new tissues have come about, presumably because the mutations have been tethered to a jumping gene that has spread the mutation across the genome. Viruses sort of do the same thing as well. So, you know, about 8 to 10% of our genome are ancient viruses that invaded our genome and got knocked out. I wonder how many of the viruses that invaded our genome then go on to become jumping genes because they already had that predisposition. There's a definite relationship. They already have the machinery, boom, they're there. So, there is that piece as well. But there's also a case where viruses invaded the genome. You know, not all viruses obviously invade the genome. SARS-CoV-2 doesn't. So, disclaimer, you know, but there are some, yes, there are some that do, and there are a lot to do, and they can they can stay like fossils in our genome after they've been knocked out. They sort of sit there like in a graveyard, like an ancient graveyard old viruses in our genome that might have invaded hundreds of millions of years ago. But some of them actually have been converted to a purpose, you know, that they've been put to use because they can sort of make a protein that's useful. So, some of the proteins in pregnancy, a protein that's, you know, like seems to be involved in the formation of memories in humans. So, I guess the general point here is that our genome is so full of surprises that, you know, that it's really telling us a whole lot about evolution and the origin of novelties and how new inventions come about. And that when you take that exciting aspect of biology, molecular biology, and merge it with the exciting aspects of paleontology, which we can now do, find, you know, target rocks to find fossil intermediates, it's a particularly exciting time to be an evolution about. What are you most excited about looking forward? Like what are the some of the big questions that incorporate these things? Well, full disclosure, I get excited very easily as you probably tell. But, you know, there are so many things that excite me, both happening in my lab as well as other labs. One of the things that excites me a lot is that is understanding the evolutionary and genetic basis of rebuilding whole organs, regeneration. That is, if you look at a salamander and, you know, if they lose their limb, let's say it gets bitten off in nature, they will regrow that entire limb, just bones, muscles, nerves, skin, the full pattern, right? What's originally a stump will regrow. Now, don't you wish we had that? That would be a wonderful thing to be able to regenerate spinal cords and limbs and, you know, all the circuit stuff. The fact of the matter is, if you look at the diversity of life, that ability to regenerate seems to be primitive, that our branch of the tree of life lost it. So, and the question is, what is the, what are the genetic and other elements, other aspects that enable regeneration that we don't have? And to some extent, one has to take an evolutionary perspective to do that. Like how was it lost? Why was it lost? What happened when it was lost? And why was it lost? I think that's, that's really an interesting question. Sure. And a lot of it may be related to immune survival, right? Yeah, no, exactly. And, but it does come at a cost. And, you know, a lot of these creatures are also aquatic, you know, so they can, so if like a, if an aquatic salamander loses an appendage, it could still move around while the appendage regenerates. But if you have the animal, four-legged animal running on land and it loses a leg, well, sorry, you don't have, you can't wait a month or two, you know, your fodder for other predators. But the, so it would come at a cost on a land living animal. But the evolution piece is tethered to this. How was it lost? And how can it be recapitulated? What do we need to do to bring it back? Even partially even. And I think that's a very hot area research because there are molecular tools now where we can see in a tissue or a cell the entire suite of genes that are turned on, you know, and we can look at that over time. And then we can look in the genome to see what are the control sequences that control that and what triggers them and, you know, all this sort of good stuff that really weren't available, you know, a decade and a half ago. And so I think that's a particularly exciting time that I'm, for that research. And I'm excited about that. But I'm also excited about the stuff we find in the fossil record that is just mind blowing. I mean, there's all kinds of interesting new discoveries on the Argentine tetrapods, the invasion of land. I mean, since the discovery of tiktok, there's been some really great fossils discovered in other parts of the world that even provide even finer resolution of the are all those fossils kind of up in the northern hemisphere? Well, yeah, most yes. So I'm not, I wouldn't call polar regions. Polar regions. Yeah. So there's one from Quebec, El Pista Stegas. We're not looking as much in Antarctica to be able to say. We're going to Antarctica to look for them. We have, you know, we may find one. Yeah, we haven't been there in a while and Covid sort of shut that down for a while. But yeah, no, no, there's a creature from Russia, partial one, there's a creature from Latvia, there's a creature from Quebec. There are others. New slash, we found another one ourselves somewhere. I can't tell you because it's not working, but there's others coming out. You know, so there's a lot of stuff happening. And, you know, so it's providing so it's a wonderful case where a we can provide more resolution to understanding a great transition and evolution through the fossil record. But I'm also really excited about the developmental piece of that. You know, as I said earlier, some of the genes that build our hands and feet, the present and fish fins, building the terminal end of fish fins. So we're now asking question, what do they do? How do they work? How are they modified? What are the genetic differences between fins? And I'm sure there's yet with the molecular work, there's so much that can be done with fish embryos and working to see looking to see how you can change them, what molecular changes take place to lead to specific structural changes. Yeah, that's right. Exactly. Yeah. I would love to know also in the book you are working, you talk a lot from a historical perspective, bringing through stories of great scientists, Darwin being one of them and various others who he debated with and who contested these ideas. And it struck me that it's that it is a process, you know, the scientific endeavor of coming up with an idea, putting it out there, other scientists debating it and contesting it, and then time and evidence amassing enough to change the way that we look at things. And I'm wondering how you see where we are now with the current molecular evidence and what kind of controversies may or may not or what conversations may or may not last the test of time. Yeah, it's a good question. So I mean, one of the things I should say just an aside, you know, when Darwin came up with this theory, we had no notion of genetics really. We had no real notion of intermediate fossils. It was pretty darn bold. And one of the things I like to do in the book is not to give you the same old characters that you might have heard before, but to really pull new voices in that have been a part of the conversation to try to find those voices. They're often women actually who contributed to the general knowledge, but might have not been as recognized as some others. But if you think about where we are at this moment in evolution and studying genetics and so forth, you really have to ask the question is, to what extent do environmental traits impact the genome over several generations? Because there's always been this case that there was a firewall between genes and environment in terms of heredity, like the acquisition of acquired traits. But that may not be as locked as we always thought. Now, I'm not going to say that's a major force of genetics, but it might exist and it might exist in a way that has an impact on evolution that we haven't thought about before. The other that is increasingly important and that I think is kind of a big deal is actually sharing genetic information among different species. That how that genetic information can jump from one species to another, either through viruses or through some other factors that are involved. And I think that sharing a genetic information is really big. And then the other piece I think is we tend to view evolution as not linear, but you have an invention that usually appears in one group and that's really cool. But the fact of the matter is we find the independent evolution of the same traits again and again and again in evolution. It's kind of like just in technology, that's why we have patents and a lot of lawyers getting employed because some people come up with the same invention independently. Well, evolution does the same thing over billions of years of the history of life. And I think that's going to be, I think to some extent, more of the rule rather than the exception in the coming years. We shall see. And I think that's a wonderful way to kind of wrap up our conversation here because it kind of ties everything together. Where can people find you and find out more about your book, which is available now? Yeah, I have a website that they can log on to that. If they want to find me in general, they can see the Interfish documentary that we did a number of years ago for PBS. It's still online at the Howard Hughes Medical Institute website. Yeah, I'm online. I'm on social media on Twitter, on Instagram, Facebook, all that good stuff. It's been wonderful getting to talk with you about your work and your thinking and your labor of love in your book, Some Assembly Required, which I like to think I was assembled. It was all required. It was all required, that's right, necessary and sufficient to make us who we are. So thank you very much and thank you everyone for joining me for this special interview broadcast of This Week in Science. We will be recording as usual tonight at 8 p.m. Pacific time and we will be joined by a guest commentator this evening, Natalia Regan, and we hope that you have a very Sciencey Wednesday between now and then. We'll see you soon.