Sean Carroll's Mindscape: Science, Society, Philosophy, Culture, Arts, and Ideas - 88 | Neil Shubin on Evolution, Genes, and Dramatic Transitions

Episode Date: March 16, 2020

"What good is half a wing?" That's the rhetorical question often asked by people who have trouble accepting Darwin's theory of evolution by natural selection. Of course it's a very answerable question, but figuring out what exactly the answer is leads us to some fascinating biology. Neil Shubin should know: he is the co-discoverer of Tiktaalik Roseae, an ancient species of fish that was in the process of learning to walk and breathe on land. We talk about how these major transitions happen — typically when evolution finds a way to re-purpose existing organs into new roles — and how we can learn about them by studying living creatures and the information contained in their genomes. Support Mindscape on Patreon. Neil Shubin received his Ph.D. in organismic and evolutionary biology from Harvard University. He is currently the the Robert Bensley Distinguished Service Professor and Associate Dean of Biological Sciences at the University of Chicago. He is a member of the National Academy of Sciences and the American Philosophical society. His first book, Your Inner Fish, was chosen by the National Academy of Sciences as the best science book of 2009, and was subsequently made into a TV special. His new book is Some Assembly Required: Decoding Four Billion Years of Life, from Ancient Fossils to DNA. Web site University of Chicago web page Google Scholar publications Wikipedia Amazon author page Your Inner Fish on PBS Twitter

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Want to drive CarMax? Hello, everyone, and welcome to the Mindscape podcast. I'm your host, Sean Carroll. And as I'm recording these words, we're in the middle of a proto-pandemic with the coronavirus, the COVID-19 disease that is happening because of this. I am certainly not an expert in viruses or pandemics or anything like that. And this episode is not about viruses or pandemics, but it is about evolution. And, you know, this is part of why we get pandemics.

is because all these little microbes bless their hearts. They keep evolving, clever new ways to deal with us, even if it hurts us in doing it. And it turns out, when you go into the details, that we human beings sometimes take advantage. Like, as you'll learn in this podcast, human DNA has a certain fraction that is just borrowed wholesale from virus DNA. In cases where we encountered a virus and we didn't just combat it, we absorbed it or at least absorbed part of it. it's part of the whole question of how transitions happen in evolution. You know, when Charles Darwin first invented the idea of natural selection, he had the idea that it was more or less gradual, right?

That there were slow changes, minor changes, and some of them would catch on, develop and grow, others would be less successful. But we do see examples of major transitions, whether they happen quickly or not is a complicated thing, but there are transitions like the first flight, right? You know, the first animals that could actually fly and develop wings, or the first climbing onto land on the part of aquatic animals. So this has always been a question for Darwinian evolution. How does that happen?

How does a fish develop the right organismal abilities to live on and flourish on dry land? Like, it's not teleological. evolution is not based on goals toward future success. So the fish can't think to itself. I would like to be able to get up and get that yummy food up on land. Let me develop some feet and some lungs and the ability to do that. So today we're talking to Neil Schubin, who is a quite well-known evolutionary biologist. He is a distinguished service professor of organismal biology and anatomy at the University of Chicago. Very well known, of course, for being one of the co-discoverers of Tietalik, the fossil that represents a crucially important transitional stage, the transitional stage precisely from being a fish, swimming in the water, to being an amphibian living mostly on land. It's a little fish-like thing that has the basic, very primitive versions of feet and hands

and the ability to breathe air and so forth. So Neil has some evolution of his own in the research that he does, mostly from going out there and hunting fossils and doing paleontology and learning about the evolution of life on that macro scale, to being in a lab and doing molecular biology, understanding how changes in DNA, both the actual coding for proteins, but also how the DNA we have is regulated and expressed, can lead to these major transitions in evolution. I mean, what actually happens in the DNA of a fish to turn it into something that can climb about on, land. It's an extremely exciting field because it's one of these things where obviously we've

learned a lot, but there's still a lot left to learn. And as we discuss at the very end of the episode, it's a rapidly changing field in part because we are developing the ability to make these changes in DNA ourselves. So what used to be more or less gradual changes in how organisms functioned can be very, very rapid because now we can have teleology. We can actually plan what might happen next. So it's a fun episode. Neil is a wonderful science communicator. He's the author of a book called Your Inner Fish, which tells how things that are still in your body right now were first developed in the context of when our ancestors were, in fact, fish. And he has a new book coming out, literally tomorrow, as this episode is being released, called Some Assembly Required,

decoding four billion years of life from ancient fossils to DNA about these major transitions and evolution and how we are learning about them through studying DNA. So let's go. The 26th National Sports Collectors Convention is almost here, July 29th through August 2nd in Rosemont, Illinois, just outside Chicago. This is the ultimate collector's experience with over 1,000 dealers, 100 plus superstar athletes signing autographs, and more than 100,000 fans all under one roof. From vintage and modern sports cards to Pokemon memorabilia live breaks and can't miss

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That's homeserve.com. Not available everywhere. Most plans range between $499 to $11.99 a month your first year. Terms apply on covered repairs. Neil Schubert, welcome to the Mindscape Podcast. Great to be here. We're going to be talking about evolution, natural selection, Charles Darwin. I want to let everyone know right from the start,

official Mindscape podcast position is that evolution is real. And we don't really, we're not going to be discussing whether or not evolution happened versus creationism or anything like that. I hope that's okay with you. Yeah, I didn't do that in the book either, so that's good. Yeah, that's not why we're here. You go other places for that. But given that evolution is real, given that Darwin was roughly speaking right, there's certainly a lot of work to be done, right, in figuring out exactly how it happened. Is that a fair way of stating it?

And that's good news because that keeps people like me employed. I mean, and what's happened recently is just we've had game-changing technology, both of the ways we analyze fossils, but in molecular biology and computation, that really changed things, you know. And so many of the questions that Darwin had and many of the ideas he had are still relevant, but boy, are we learning new things. Yeah, yeah. And it's always, you know, one of those things where when you solve one problem, you open up multiple new problems, right, multiple new puzzles. And I think that people who are not embedded in the scientific process might feel like there's just more and more puzzles that you guys are inventing, whereas

it's actually, you know, there's more and more knowledge being gained at the same time. Yeah, and, you know, sometimes you actually get to ask new kinds of questions, more powerful questions in many ways, more precise questions, maybe more global questions. So, you know, the questions never stop. They just change, and as we gain answers, we gain new questions. Yeah, so you have a new book coming out called Some Assembly Required, Decoding Four Billion Years of Life from Ancient Fossils to DNA. Congratulations on that. Oh, thank you so much. And you've written a couple of other books. You know, your sort of breakout one was your inner fish about the discovery of, I always say tectalic, but I'm told that's not the wrong pronunciation, right?

Well, that's actually right in some quarters, but we say tictolic. Tictolic, okay. Yeah, so if you go to the Inuit, it's just an Inuit word, an Inuit name, it would be Tictolic. Oh, really? But Tictolic is what we've been saying, yeah. Oh, I'm definitely going to stick with the Inuit. Definitely. So we'll tell that story a little bit.

But first, just to put things in context, one of the things that you still want to understand, if you're a good natural selection evolutionary biologist, is the question of missing links and big transitions in evolution, right? I mean, the joke is that whenever you find a missing link, you've created two more missing links because you now have one species in between two other ones. But this is a good puzzle for biology, is that right? Oh, it's a wonderful one. And in fact, it's the one that drew me into the field.

And in realizing that, that's how this book came about, was realizing how important those questions are, the great transitions in evolution, and some of the misconceptions that we have, all of us, about those transitions, missing links being one of them. So in what sense is, is there a slogan that says

the idea of missing links is itself a misconception? Well, there should be. But as somebody who's been, you know, who's claimed to have found a missing link, other people have purported that Tictolic is. But the reality is evolution is, it's a hugely branching tree. It doesn't take a straight-on path.

And, you know, when we talk about links, which there are, number one, they're found. They're not missing. But number two, you know, the path of evolution is often very unpredictable. It has lots of twists and turns and goes backwards and forwards. And it's not a straight path, a linear ladder. It's a hugely branching bush of change. That, you know, that goes in many different directions.

So the missing link concept, I mean, the part of it that's right is link, is, there are links among species. But what underlies that narrative, however, is the assumption that evolution acts as a ladder of progress, of change, of one form inexorably giving rise to another that's, you know, that looks sort of like, that looks the same but different. There are aspects of that that are true, but it's that linear narrative that, that I think we're finding as we study fossils and genes, this really doesn't hold up. Yeah, and your book certainly does a good job of explaining the messiness of it all, which is, you know, like you say, full employment for scientists.

Yeah, it's a beautiful messiness. Those, the mess is the message, you know, and so we can get into that. But it's, that's half the fun of this, you know. But that's why people should become physicists instead of biologists. It's way cleaner. Biology is way too messy. Yeah, we're a total mess. So one of the very most obvious links that one might want to fill in, whether you call it a missing link or not, is between fish and land dwellers or amphibians or whatever.

And that's where Tik Talik comes into the story. So why don't you tell us just the wonderful human story of you and your team discovering that and what it all meant? Well, it began, as I described in the book, actually, it began in my second year of graduate school. I didn't know what I wanted to do for my PhD. I knew I wanted to study evolution, but I thought maybe I want to study mammals or I don't know. I didn't know. And so I took a survey course on evolution. And each week was a different greatest hits in the history of life.

You know, you'd go from one great transition to the next. And the professor showed this beautiful slide of a fish on one end and an amphibian, a tetrapod, a limed animal on the other with an arrow connecting them. And it was like kind of what we knew about that transition from water to land. And I remember looking at that slide thinking, golly, I want to work on that problem. And I want to find fossils that do it. And so, you know, with colleagues, we set off on a multi-year quest to find an intermediate between a fish that lives in water and a limb-down. animal tetrapod that lives on land. And we know, we used the rules of paleontology. You know, we didn't invent new methods here. We were using sort of the tried and true, you know,

perspectives of field paleontology, which go as follows in simplified form. If you want to find a key intermediate fossil, say, a transitional fossil, say, between, say, fish and tetrapods or between, you know, birds and reptiles or reptiles and mammals, whatever, you know, you look for places in the world that have three things. You look for places in the world that have three things. You look for places in the world that hold rocks of the right age to answer whatever question interests you. So if you're interested in the fish to limbed animal transition, you know, you're going to look in rocks about 380, 375 million years old or so. You'd look for places in the world that have rocks of the right type to hold fossils. Obviously, not every kind of rock does that. And as a

geologist, you start to learn the catalog of environments and rocks that are likely to preserve the best fossils. That's as much art as science, by the way, and a lot of induction there. And then the third part is you look for places in the world that not only have rocks at the right age and the right type, but the rocks that are exposed and accessible. You know, it makes total sense, right? You don't want rocks that are buried 12 miles underground or that are in the side of Mount Everest. You or in a politically and viable place, a war zone. You know, you need accessibility.

And so those are the filters, right? So, you know, the world is a big place. So the point with that last one being that, you know, erosion and plate tectonics, et cetera, are constantly exposing new layers. And so you're going to go for, look for the layers. which have the kind of rocks that you want. That's correct. That's correct. And so you can actually go to geology libraries, which is what we did in the 90s or do it online,

and you can get aerial photos, you can get geological maps that give you the kinds of rocks in a country's border. You can dig out papers on the local geology to find out what kind of rocks are there, and you can put all this information together. So that's what we're doing in the 90s. And we, you know, looking for rocks at the right age, about 375 million years old and so forth. our first gig was in Pennsylvania because my first job was outside it was at the University of Pennsylvania in Philadelphia

and I and I grew up there as well and so I knew the place and I also knew that there was a lot of Devonian age rock in Pennsylvania throughout the state so it became the first part of our hunt was looking at the Devonian age again 365 to 375 million year old rocks in Pennsylvania and turns out we you know we didn't have a lot of exposure so we worked on road cuts. You know, when PennDOT, Pennsylvania Department of Transportation would come in to build a new road, we'd, you know, we'd get in there and look at the rocks. And that was amazingly successful. It really was. We, you know, we started to find early tetrapods, early limned animals. We

found all kinds of fish. It was just a remarkably productive program. But my colleague in this, Ted Dessler, was a student at the time, and now a colleague who works on all this stuff with me, we realized we had a problem. We were in rocks that were too young to answer the question. We wanted to find a fish with a fin with limb bones inside it that had a head like a tetrapod, like a flat head, not a conical head like a fish that had a neck or things like that. And we weren't finding a lot of that. So we're in rocks are way too young to answer the question. So back to the drawing board.

And so it turned out one thing led to another and we settled on a region of a rock up in the Canadian Arctic that extends from about 1,500 kilometers. from Melville Island in the west to Ellesmere Island in the east. And perfect. I mean, rock 375 million years old. Rock that was produced in ancient rivers and stream, much like the Amazon Delta today. It's in the Canadian Arctic, by the way. That tells us how different how much the world's changed.

And then rock that was exposed by ice and water and so forth. So we had all our variables maximized at this spot. So starting in 1999, we began expeditions. there. Slightly more exotic than the hills of Pennsylvania. Yeah, quite a bit. You know, you're taking a team of six people. There are polar bears up there.

It's daylight 24 hours a day. We're 300 miles from the nearest village, which has 170 people at 80 north latitude. I mean, it's pretty extreme. And for those reasons, it took us a while to be successful. I mean, a season up there would be about four weeks. And so we started 99, did four weeks then, 2000, did it again. And each year we made a little. progress, but we never really found what we were looking for until 2004. We had found a layer

with lots of fish bones in it. And we were digging this layer. I'll never forget this day of my life. It was like July 17th, 2004. We're in this layer, cracking rocks, finding fossil fish. Nothing we'd be talking about. But one of my colleagues in the pit with me cracked a rock and said, hey, hey, Neil, what's this? And I came over and I looked at it. And as soon as I saw that, I knew we had found what we had spent six years and lots of money. And I was that. And lots of money. lots of sprained ankles looking for. And what it was was a snout of a fish, clearly had fish bone.

The texture was classically fish. It was clearly the front of a skull, but it was clearly a very flat skull. And so early limbed animals have flat heads. We were looking for a flatheaded fish. So I said, here's a flatheaded fish looking right out at me in the rock. It was a lot of celebration.

So we ended up removing the whole thing. It's about four feet long, a little over a meter, and then pulled it out. And then as we did that, we found four more of these things. And since then we found about 20. So they're not at all rare.

And then we got these things back to the lab. And the rock was removed grain by grain. And, you know, first we saw it had a fin, great. But then we saw inside it had a humorous, an upper arm bone. It had a radius and ulna in there. It had a wrist. It had even things that might compare to digits, fingers and toes. Things most fish don't have.

Yeah. But in a fin. Clearly it had fin rays, you know. And this thing clearly had a shoulder that was part fish, part limb down. animal had that sort of set up, yet it had scales, yet it had fish like bones in the skull. So it was a real, you know, mosaic between characteristics of fish and limed animal. And it was an animal that had lungs and gills, had fins with limb bones inside. You know, it's exactly what we were looking for.

And it tells us a lot about how this transition from water to land happened, you know, it's real physical evidence of that. And it wasn't lost on us that this was, when we were working on this fossil initially, it was 2000. We found it in 2004. We did most of the work in 2005 and six. illustrating it. There were trials going on where people were, you know, suing to teach intelligent design creationism in the schools. You know, and here we had on our desks, these

fossils. It was quite the time. As you can imagine. I mean, presumably they would just say, you know, yeah, you glue together a fish with salamander or something like that, right? I mean, yeah, well, you know, but we actually recorded us taking it out. I mean, this was just, and the wonderful thing is that about this example, why I love using it to teach, not only because it's, a huge part of my life, is that we used the tools of evolutionary biology, of geology and stratigraphy, of historical geology, to make a prediction. Right. You know, we didn't go randomly to the Arctic, you know, and we didn't just stay there, and we

stayed there for six years. We stayed there for a reason. We had a, we felt we had a very strong prediction. We, that the, you know, odds were in our favor if we stuck with it long enough, um, that we would be, uh, successful. And, yeah, and that's, that's what happened. It's a predictive science. It's not merely a matter of,

history. That's correct. And it's, you know, you can you can put the odds in your favor by knowing a lot about the evolutionary history of the groups you're interested in, the dating and ages that those fossils first appear, and then knowing a lot about the environments that creatures likely lived in. Once you do that, then you can make your predictions, and that's the toolkit. You've probably heard of Peloton. It's a game-changing home exercise system that lets you do your cardio workout with a bike right in the comfort of your very own home. And the best thing is that right now, there's a new 30-day home trial that will let you try out the Peloton bike for yourself. I've ridden it.

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So try it for yourself. Learn more about Peloton's 30-day home trial at OnePeloton.com using promo code Minescape. That's O-N-E-P-L-O-T-O-O-N-Cate to get started. If you don't find that the bike is right for you, they'll pick it up, full refund, worry-free. You sort of skipped over one thing, which I think is absolutely fascinating. So once you've found the rocks you want to look at, and then you go up there for years on end, what is the actual process of looking through the rocks for a fossil like? I mean, I can imagine that I'd be walking through rocks for a long time and not see any fossils.

Part of it is just you have a trained eye, but there's probably more to it than that. Well, it's getting a trained eye, definitely. There's a couple things that fit together. One is you train your eye. And if you were to come on an expedition with us, you'd first get there and you'd think we were magicians. We'd be picking up rocks all over your feet. But after a few days, you'd do it yourself. You know, that pattern recognition system that we all have kicks in.

Takes a few days, but you'll learn it. And whenever I go to a new place, I have to learn out of find new fossils. Each rock kind of rock is different. But what we do is, you know, you get up in the morning and we have geological maps. We have our aerial photos. We have a good knowledge of what kinds of rocks are exposed everywhere around us, so which hills hold which kinds of rocks. So we decide in the morning which rocks we want to visit, so we'll walk to those,

and we'll literally follow layers for miles looking for bones that are weathering out on the surface. And it's just painstaking. You've got to stick to it. And once we find something that's weathering, then if it looks good, we'll dig out the layer, try to find the layer of the fossils are coming from, and if it's any good, we'll put a whole team on removing the fossils in that layer. That's essentially what happens.

And so, you know, success, what matters here? What matters is developing that eye, developing a knowledge of the geology of the rocks you're working on, being really patience. Yeah, I think that's... There'll be whole days, whole weeks where you're not finding stuff, but you've got to stay on point. And sometimes that's not easy, you know,

if the weather's lousy, if, you know, you're stuck in the Arctic and you want to get you home, I mean, you know, there's lots of other psychological things that kick in as well that, you know, that you have to think about up there. But all those are variables that, you know, that are related to success. Well, you know, we've done the experiment. I have gone on to Wyoming and Montana with your colleague Paul Serino, digging for dinosaurs. And I'm just not really very good at distinguishing their rocks from anything else. Well, I got news for you.

I was no good either when I was in graduate school. The first expedition I went on, it was like 1980. 83, my first year in graduate school, I was invited to look for fossil mammals, which are really small. I was an utter disaster. To the point where one of the senior people told me, like, you know, you don't have a future this kid. Just stick to the theoretical side. You know, by the way, I had never camped before that.

You know, I was just such a nerd. And so this all was new. But then, you know, I decided I wanted to do it. And just like anything in life, which is your decision, you can learn it. Exactly. And I love the fact that the book that you wrote about this was not just, hey, we found, you know, transitional organism between fish and amphibians, but the fact that the relics of that transition are still within us today, right? That's what it really means to have our inner fish. And it's a reminder

that the transitions are gradual and continuous from very early times to right now. That's correct. I mean, so the conceit of that book was, you know, that fossil was just a waypoint, but really when you start to look at anatomy and development and molecular biology, what you start to see is there's billions of years of artifacts of billions of years of history inside our own bodies. And you see that in the genome. You see that in our cells. You see that in our tissues, our organs. You know, so whether you look at our skulls, limbs, and so forth, we can see a layer after layer of evolutionary history inside of us. So that was the story that I told in Inner Fish. And, you know, that was really an extension of a lot of the teaching I did, because at the time I was also,

At the time we discovered, Tictolic, I was teaching human anatomy to medical students here in the University of Chicago Medical School. So I was like, enabled me to connect the dots in the way I probably wouldn't have done in the same way previously. I think that hiccups were my favorite example, right? Can you explain why we have hiccups? Yeah, well, we have hiccups. You know, it's basically a spasm of the frenic nerve. One theory that came out of some folks in Canada about a few years ago was the idea that that response that is a very calibrate. stereotypical response of nerves firing and muscles firing in consequence that there's a pattern inside our central nervous system that causes that pattern to occur. That pattern occurs naturally elsewhere in the wild in one place where we see it is in frogs and tadpoles, which use a form of a hiccup and that neural response to actually breathe with water. And so what we'll see is there's

these antecedents that we see in other animals for things that are, you know, we think, think are distinctively human when in reality they're not. Yeah. So we can get into exactly sort of the purpose, I think, of the main theme, let's call it that of this podcast, which is this is, the Tectolic does represent a major transition from one way of life to another. Can you just say a little bit for people who don't know anything about, you know, what was its motivation for climbing up onto land and how did that really work?

I mean, it seems like something that if you're just underwater and have a happy life there that climbing up to a different poisonous environment is not your first idea. Well, it helps to compare water and land. And so there's probably not one reason. There are probably many. But if you look in the Devonian and what lived in the water at that time, you had big fish, you had small fish, but pretty much all of them were carnivores. They were all predators.

So it was a fishy-eat-fish world. And by the way, you wouldn't have wanted to swim in these Devonian streams. There were 15-foot-long predators filling the crocodile kind of an inch. Giant predators with teeth the size of railroad spikes, you know. So, yeah, so it was a very predator and competitor intense world in the water. But if you look at land at that time, there are plants on land. There are invertebrates. There are food sources on land.

There are a few competitors and certainly no predators. So, you know, anything that would sort of, any trait that would allow a creature to avoid that the water, get away from the predators and the competitors, into the mudflats, into land would probably be favored because there was a world of opportunity. with food stuffs on land without competitors or predators. There are probably lots of other reasons as well. Things like Tictolic and its cousins in the Devonian were not fully landliving. They were living in the shallows and the mudflats. So there's a continuum between these environments as well. So lots of reasons, but there are lots of good reasons to get out of the water.

You can think about it. If it's a fish-eat-fish world, there's lots of strategies. You can get big because big, fishy little fish. You can get armor. which a lot of fish do, or you can get out of the way. Get out there. I think our distant ancestors were the ones who got out of there. But it's not Lamarckian.

You can't, as the fish, say, boy, there's a lot of yummy food up there on land. I think I will turn my fins into feet, right? I mean, there have to be all these little transitions. That's a really good point. It's not that. It's actually, it's natural selection. And that's what some assembly required. The new book really is about in showing how that happens.

So the, it's, you know, when you think about the wall, water to land transition, it actually exemplifies other great transitions as well and showing one really important thing. That is pretty much every trait that we associate with one of the great revolutions in the history of life, say limbs or arms and, you know, the invasional land, lungs in the invasion of land, feathers in the origin of flight, you know, walking on two legs in the origin of humanity. Pretty much every trait that we associate with the revolution is not associated with that revolution. It came about millions of years before. Right. You know, and that's the big thing, you know, and one of the quotes that leads off the book is one of my favorite ones from Lillian Hellman, who lived a

fairly hard life. And she said, you know, nothing, of course, ever begins when you think it does. And that is a great motto for thinking about evolutionary change, you know, nothing begins me. It always begins well before. It's always repurposing something else, right? It's repurposing, you know, and it's repurposing and modifying and then repurposing again, co-opting, duplicating, merging. I mean, it's all these things. It's tinkering in some very profound ways. And we get to see, you know, glimpses of that tinkering in the fossil record. We can see the pathway it took.

But when we look at genes and we look at development, you know, we look at molecular biology, we begin to see the mechanisms behind that kind of tinkering and repurposing, which is, you know, really fabulous stuff. So I can imagine, you know, it might be much harder for that fish to climb up. on the land if it didn't have fins in the first place? Or flippers? Flippers, should I say? Yeah, it had a sort of a flipper-like limb. It basically had a shoulder.

It had an elbow and had a wrist. And it had part of the fin that the terminal end of the fin that could serve as a palm. This is a fish that can do a push-up that can even walk in funny ways. And by the way, this fish also had lungs. So you can imagine that these fish, with all this gear, you know, living in water, walking on the bottom of the water or maybe in the mudflats, It was already set up to jump into land when the need happened and to refine those structures and to modify them and repurpose them in new ways. I think maybe to the people who are not experts, the fact that it had lungs is even more impressive and surprising than the fact that it could develop feet. Because as long as you have flippers, you can imagine morphing them into feet.

But if you breathe through gills, why do you also have lungs? Yeah, that's great. And so this is actually something that was discovered in the 1830s. We've known this forever. Yet, you know, if you talk to people, they always think, well, lungs arose when, you know, of course, they're related to living on land. No, they're not. They originally came out in creatures living in water. And we've known that since Napoleon's expeditions to Egypt in the early 1800s and ever since.

And what people started to do is they discovered, you know, in dissecting new kinds of fish that they saw in Africa or in South America or in Australia, they found that some fish have lungs, real lungs that are exactly. like ours in many ways. And in fact, if you look at a lot of fish, a lot of fish have a air sac that is connected to the gut tube or related to the gut tube in development and development. And, you know, in some of those fish, that sack becomes lungs and others that sack becomes swim bladder, which they use for buoyancy. So this air sac presence in fish is really ancient. And in fact, an air sec that functions as a lung is ancient still. So, you know, what is it doing? Well, in fish that have lungs, they have both gills and lungs.

And more often than not, they're using their gills. They're, you know, sitting in water, just like any good old fish and breathing, right? But water, you know, the oxygen concentration in water can vary a lot. It can vary a lot from month to month, season to season and so forth. And so there are times when the oxygen content of water is not sufficient. to support an animal's life. And what they'll do is that in those cases, they'll go to the surface and actually gop air into their lungs and then go back down. And so lungs are sort of an accessory organ that allow fish to exploit water that has variable oxygen concentrations throughout

the year. And there are lots of strategies that fish have to do this. Some have lungs and others breathe through their skin. Still others will vascularize parts of their mouth and use that as a respiratory organ. So there's lots of little different indentions that happen in evolution to allow fish to breathe air. Air breathing in fish is very, very common. But lungs are a very ancient one. And so our distant relatives who originally took the first steps to walk on land, they didn't need to involve lungs, though you're already existed.

Is it safe to say that the lungs always came from swim bladders or air sacks or something like that? Was there some prior purpose that had developed? Yeah, it's safe to say that the lungs actually originally rose as a developmentally as an out pocket of the gut tube. So during development, you have the tube that forms the gut, it develops there. And then it out pockets, it forms an out pouch. And in some fish, that pouch becomes lungs, and others it becomes swim bladders. So they're related developmentally. But the whole thing is it's the common developmental process that gives rise to both.

And pretty much all fish have, you know, one or the other. Yeah, good. And this is a good segue. way, thank you for doing my work there, because one of the lessons of your book is that one of the major sort of resources for doing this repurposing is tinkering with our development, right? That's right. There's this famous, but slightly exaggerated idea that ontogeny recapitulates phylogeny. Tell us that story a little bit, and maybe we can work salamanders in there at some point because

the salamander stuff was just amazing. Yeah, that's really cool. So, you know, ontogeny recapitulates phylogeny. A lot of us learned it in high school. I learned it in junior high. And it was like a little jingle we'd all sing in like, you know, the third week of evolution or something like that. And, you know, as most people know,

it's this notion that, an older notion, that claims that during the course of development, going from egg to adult, you know, through the different stages of embryology, organisms, creatures would track their evolutionary history. So if you look at a mammal, it would go through a fish stage, an amphibian stage, a reptile stage, and so forth. And this was right after Darwin wrote the origin of species, Ernst Heckel, great German biologists, really promulgated this theory, pushed it along. And there are other versions of recapitulation as well.

There was one that actually came out before Darwin. And that basically said that, you know, creatures look most similar as embryos. They tend to look very different as adults. that's actually a much more modern concept, even though it's the older one in many ways. But anyway, these were very foundational concepts. It turns out that, you know, the biology is a world of exceptions, particularly for ontogeny recapitulating phylogeny. And there are so many exceptions. You should probably tell us what ontogeny and phylogeny are.

Yeah, sorry about that. So ontogeny is another word for development. Phylogeny is another word for evolutionary history. So development tracks evolutionary history. That's re-capitulate. Antogyni recapitulates phylogeny basically means, in English, development tracks evolutionary history. But that was a very dominant theory worldview for a period of time. It turns out to be wrong, though there are cases where it does that.

So there are some cases where we do see in individual traits that the development will track evolutionary history. But it's certainly not true as a sort of a law of nature like Heckel and his. contemporaries proposed. So it does seem to be true that in the embryos, et cetera, of various species, you see features that are in common with very, very different species, presumably because of our common ancestry. That's correct. So, you know, we see a ton of that.

In fact, that's, we see so much common in development. And that's, you know, when you look at an early embryo of a fish and a human, you'll find enormous number of similarities in the skull bones and the digestive. system and the extratory system and so forth. But it's not like we track evolutionary history. It's just that we begin from a common stage of development, more or less. Or our early stage of development tend to be much more similar is kind of the idea there. But, you know, the relationship of development, embryology, to evolution has long been a

source of fascination for scientists in my field. I mean, it's really the embryo has always held this special place because you think about it. You know, here I'm studying evolutionary history. I'm looking at great transformations, you know, in the history of life. But what happens in development? Great transformations like happen every hour. You go from, you know, organs appear out of, you know, you begin as a single cell. Yeah.

The cell doubles and doubles and doubles and doubles. And eventually you get germ layers, these different layers that form different tissues of the body. And then the heart emerges, central nervous system emerges. These things emerge over time. And part of the fascination, which I felt as a graduate student, You know, when you're looking in an embryo, you're looking at an organism being built. It's a really beautiful thing.

And when we can compare, you know, embryos of different creatures, say a fish and a mammal, you begin to see how you can begin to explain the differences between them by differences in the way they're built, right? And that's a very powerful way to look at evolution. Which reminds me, I wanted to ask a little bit more about the history of Darwin. And this is out of order, but that's okay. You know, Darwin correctly gets credit for natural selection, et cetera. But there were ideas floating around that, you know, species evolved in some very generalized sense without necessarily all of the mechanisms of random mutation and natural selection, right?

Oh, that's correct. I mean, the notions of evolution were around before Darwin. You mentioned Lamarck. He was before Darwin. Darwin's own grandfather, Erasmus Darwin, had a notion of evolution. And in fact, when Darwin was working in his theory of evolution, other people were coming up with it at the same time, Alfred Russell, Wallace, and a few other people independently. So, yeah, the idea has been out there. And in fact, many of the ideas we use in an evolutionary concept originally came about before Darwin.

So this notion about embryos being very similar, more similar to one another than adults. That was something that was pre-Darwinian. Yeah, that's what I wanted to get at. That's just amazing to me. So they already had that idea even. Oh, yeah. See, they were really trying to explain diversity. You know, some of us in my new book is trying to explain diversity.

How do we know? How do we explain and understand, you know, the diversity of life we see on our planet, right? Well, people have been out after that for a long time before Darwin. It's just they weren't using natural selection as a mechanism. They saw, you know, work of a creator, but they were looking for order and rules that explained underneath diversity, that explained it. And a lot of those ideas that they developed in the pre-Darwinian context actually apply very well in the evolutionary one.

Did anyone have the idea that God did it and it was designed, but God's plan involved species changing over time from something simple to the incredible diversity we see today? I'm not aware of that particular view. Because one of the challenges for that, some listener probably would know it, I don't. However, one of the challenges for that was to accept that. You'd have to accept that species are imperfect and they go extinct. And the concept of extinction was a relatively new one in biology, believe it or not.

You know, it has its own history. But it really wasn't until soon before Darwin that people really accepted the reality of extinction. So if you don't have extinction, you know, and if species are perfect, then it's hard to have a notion of evolution. And so it's the idea of extinction was itself part. The understanding of extinction was really essential for Darwin and other people's perspectives on evolution as well. So there was still some picture that, you know, nature was kind of a perfect kind of set up and there was no reason for it to change over time. And that was part of the cultural change that, uh, Darwin wrote in on.

And that was kind of the dominant worldview. But these folks, and many of them who make it into the book, we're really looking for order and diversity, rules and diversity. You know, what explains why a fish looks the way it does and a human? And they were trying to do it in a world where these species are fixed and not changing. But in doing that, they devise tools, conceptual tools that we use today. One of them is this notion called homology, where, you know, it has pre-Darwinian roots, but it translated very well for Darwin,

the idea that you can compare similar structures in different species, you know, that you can compare a vertebra from a fish to a reptile, you know, to a bird, to a human. And you can compare the same vertebra among these different things. That was a notion that came up

in the pre-Darwinian world. But yet, you know, Darwin basically, you know, put a mechanistic, a material spin on it, basically saying the reason why you can do that is because these things share in evolutionary history, right? Let me pause for a second

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So you can create furniture that matches your own fearless style at Joybird.com slash Mindscape. That's Joybird.com slash Mindscape. You'll receive an exclusive offer for 25% off your first order. by using the Minescape Code. See how Joybird can help make your dream space a reality. Good. So this is an appropriate time to bring in the salamanders because I think this is just a wonderful example of how there is a connection between development and evolution.

Yeah, salamanders. I love salamanders. So I did part of my PhD thesis on salamanders. I just loved them, and then I did my postdoc on them. I mean, I didn't grow up as a kid who loved herps, reptiles and amphibians and stuff. But as a graduate student, I just fell in love with these little creatures. And they just have such a history.

So, you know, one of my favorite stories is August Dumariel, who was a professor at the Museum of the Natural History in Paris. You know, he and his dad were experts, academic, academician experts on reptiles and amphibians. And this is a time of discovery, sort of in the mid-late 1800s, right after Darwin, about 1864 or so. And so Dumoreal would get shipments of critters from. expeditions around the world that folks found and they'd want them to, you know, figure it out. Well, one day he gets a box with, I think, you know, six salamanders inside. And these were from Mexico. And he looks in a box and the folks sent it to him because Darwin just published his theory.

And these salamanders that he was sent, they had an aquatic tail, big fleshy lobe tail. They had external gills. They were fully aquatic. And they sent them to do morel thinking, well, here's a living. missing link, right? This is kind of like a creature that, you know, maybe will tell us something about how fish evolved to walk on land. So, um...

Did they know about salamanders at all in Europe at the time? Uh, yes, they did. Yeah, because there were, there are European salamanders, so they knew quite a bit about them, you know, just their local species. But this from Mexico was weird because it had this. This is a giant adult, fully full adult with all these aquatic

features. So he's like, oh, this is great. So he, um, so he put him in his menagerie. And salamanders are easy to care for. You can like leave him alone for long periods of time. And that's exactly what he did. And he came back after a period of time and he went back to his box. And he looked in his box and he saw his, you know, fully adult salamanders that were aquatic with external gills. But then there was a whole other type of salamander there. Fully adult reproducing big with no external gills, a fully terrestrial body, no aquatic lobe tail, no external gills. He looked at it. It's like,

these are two different genera, okay? Something happened in that box. Not just species, yeah. Yeah. It's like there was, this was a magic box. Well, he was a scientist. He didn't follow the magic reasoning. So he said, well, what is going on here? Something amazing happened. I mean, it's almost like, you know, he put gorillas in the cage. He came back and found checks in gorillas the next year. I mean, it was like that kind of thing. So he did his, he did his homework and he started to study their embryology. And he found that this difference is really a simple shift of development. And it showed how a simple shift. of development can bring about changes across the entire animal. So what happened is during the normal life cycle of one of these salamanders, you know, they have an egg, they hatch from the egg, they swim around in water with external gills and fleshy tails that are like a fin. And then at some point in their life, they swim around as aquatic larvae, right? And then they get bigger and bigger and bigger and bigger.

And then eventually at some point in their life, they undergo metamorphosis. and metamorphosis, hormone is triggered, thyroid hormone, and they lose the external gills, the tail changes, the head changes, all that good stuff. And what Dumarrel realized, as well as some other people at the time, was what happened in his box is the salamanders, the aquatic salamanders reproduced, but their offspring underwent metamorphosis,

which those other ones didn't. And so there was a, the trick there is whether you understand, or go metamorphosis or not, which can be triggered by external cues in these species. So it's really remarkable. He was able to show, and this is a huge insight, that a subtle change in development, maybe just changing, you know, thyroid hormone and metamorphosis can have changes across the body, and two animals can look entirely different as a result of that. So that work was really foundational in the sense that what it did is it turned people on to thinking about, well, what kinds of subtle changes in development can bring about some of these huge

changes in the history of life that Darwin was talking about. And it turns out one simple way is just to change the timing of developmental events, extend development, stop it early, that sort of stuff. Yeah, I mean, it's amazing to me because, just to be super clear, that other form that did undergo the metamorphosis is completely land-based. It doesn't look like it has any aquatic paraphernalia at all. Is that correct? That's right.

That's correct. Yeah. So, I mean, the body looks totally different, right? And the way it feeds is totally different, the whole thing. And it's really just a subtle change in a level of hormone at one time of development. And also the fact that it can just get stuck in that premedomorphic stage and still flourish, right? It's a perfectly working salamander, but it's an aquatic salamander. And by the way, it's really useful if the critters living in water, right?

So, you know, and think about that. Here, the whole waterland transition happens in one animal through the course of its life. Yes, that's amazing to me. That's why development's interesting, right? And here I go study fossils and look at this guy. But that's really amazing because, you know, then the hunt is on. Well, what kind of changes to development can bring about the evolutionary changes we see? Yeah.

And again, it's these changes of timing developmental events. It's now we know it's a lot of molecular changes and how genes are controlled, turned on and off during development. You know, there's, I mean, that's been a, that's been such a powerful and powerfully important tradition in my field of biology, this relationship between development and evolution. It's its own subfield now. Yeah, but I mean, you've already now mentioned something that is crucial to this story. As good as the 19th century was about figuring out all sorts of weird things about animals, these days we have information about DNA and genes that is really changing the whole way we think about this story. That's correct.

And so the predicate for all this were people like Dumoril who were studying the embryos, who were studying the bodies. But the game changer for us is really the advent of molecular biology, you know, and its power to explain. and it gives us a whole new set of tools to approach these classic questions. And some of the biggest discoveries started, well, again, they have predicates as well, but the 1980s and 1990s were quite a remarkable time, where molecular tools were getting powerful enough and cheap enough and could be applied to a number of different species that we began to see the relationships between genes and development in the embryo,

you know, how genes control that development, and how changes to genes can bring about changes to development and ultimately changes to evolution. So that has been incredibly important and incredibly powerful. And some of those initial discoveries were game changers for me in my own growth as a scientist. I had trained to be a paleontologist, and I was studying how to find fossils, you know, the techniques that led to the discovery of Tictolic, right? but I remember back in the 80s there were a bunch of papers were being published and I was made aware of them

by a fellow graduate student and showing that we were seeing in flies genes that build the bodies of these animals genes that control why a wing is in one part of the body and an antenna is in another part of the body and that was exciting enough

but was even more exciting was later papers showing that These genes aren't present only in flies, but versions of these same genes are present in salamanders, frogs, worms, mice, and people. You know, that there's a common toolkit. Versions of the same genes are doing similar things in many different creatures. And for me, that was a glimmers of a new biology. And for a lot of people, it was glimmers of a new biology in the 80s. And so that's when I decided to add the molecular biology toolkit to my own repertoire, you know, as a scientist.

And we don't think that that's convergent evolution. We think that this is just a set of genes that have been with us a long time. Oh, my gosh, yeah. These are ancient genes. And these ancient genes aren't the same, but they evolved in the distant past of animal life. And then, you know, there have been rounds of where these genes have been duplicated, modified, repurposed. Just like structures, genes are repurposed, you know. And so there's rules we see for the evolution of anatomy.

They apply very well to the tinkering, the repurposing, the co-option, the duplication. all these things that we see in the evolution of structures, they happen at the level of genes. So these genes are ancient, but they've also witnessed a lot of changes. The flies have only one set of these genes. We have four, so they've been duplicated over time. They've gained new functions and more complexity over time,

that kind of thing. I'm sure that the 80s and 90s were great, but I don't want to skip over all the really charming early technologies that were there for thinking and measuring genes and their differences and so forth. I guess I'll let you pick your favorite stories from the book, but the idea of putting little molecules in a gel and pulling them across with an electromagnetic field

to see how heavy they were. Because I think that these days were spoiled and people probably think, well, just, you know, look at the DNA and figure out what it says, but they didn't have that ability back then in the 50s, I'd say. One of my favorite stories is Sissumo Ono. Ono was a researcher at the City of Hope. California, and he was interested in genetics, hugely interested in genetics.

And his, because he loved horses and he found he couldn't train, you know, that there's only so much you can train horses. He said, if horses, no good, it's no good. It's all about the genes. So because of that love of horses and his knowledge of them, he decided to study genes, right? And so he designed one of the greatest techniques. So he looked at chromosomes, right? Chromosomes sit in the nucleus and, right, chromosomes are, you know, bundles of DNA. and he wanted to see, you know, can he characterize differences among species by looking at differences of their chromosomes, right?

This is in the 40s and 50s. And, you know, he didn't have much technology, you know, at his fingertips. What he had was a microscope, and he had a camera, and he could develop pictures with that camera. So what he did was he took pictures of, like different species. He took salamanders. He took rhinos. He took people. He would just get cells, right?

Cell samples from zoos and he would look at the nuclei and look at the chromosomes and the nuclei. So we'd take pictures of all these things. And what he did was lowest technology possible. He took pictures of the chromosomes, printed out the pictures, cut them out, and weighed them. So he would basically take pictures of the chromosomes of a salamander, cut them out and weigh them, and then take pictures of the chromosomes of a human, cut them out. and weigh them. And he used those weights as proxy for the amount of DNA in the cell.

Better make sure the Zoom was the same in both pictures, right? Yeah. Well, what he found was that the salamanders have like 10 times more genes, chromosomal stuff than humans. And he was one of the first persons using this low-tech technique to show that the amount of genetic material in the nucleus, and what we know now is the amount of DNA in the genome, is unrelated to the complexity of the organism. Yeah, I was going to say, that's not possible because aren't we, like, way more superior

to these little salamanders? How can they have so much more genetic? They could flip their tongue in a millic, their body length, in a millisecond, some of these things. So that's pretty superior. It depends how you measure it. But, yeah, I mean, we're much more complicated in a lot of ways, cognitively and so forth. And, yeah, he found that that's unrelated to the amount of genetic material in the cell. So he was one of the first people to show that, you know, the amount of genetic material

in a cell is unrelated to a critter's complexity. You know, he looked at plants like lilies. They had an enormous amount of that. Yeah, so that was a huge surprise. And then he was able to look at those chromosomes because you can add dye to the nucleus and like you can begin to see the chromosomes with little stripes on them. He began to see when he looked in detail at the stripes.

It looked like whole sections of stripes were just like repeated and duplicated. Like somebody took a Xerox machine to the chromosome of the salamander, just duplicated whole chunks of it. So he came up with a notion of with all this low-tech, technology stuff that the idea was that perhaps one of the major sources of innovation for new genetic material and evolution is gene duplication, is duplicating old genes. So that's a great way of co-opting and repurposing. And so that turns out to be a very profound discovery because the more we look at gene sequences, we can now sequence genes in an afternoon. You know, we begin to see just

how important that is that, you know, there are whole gene families, you know, which might contain hundreds of genes, you know, all related, all related to each other by history, rounds of duplication in their history. We see that in tissue and tissue or, you know, over and over again. I just love that story because here's a person who had a great idea, found a very low-tech way to test it and opened up a whole new field of research. Yeah, no, I mean, it's, it gives hope for, you know, the ingenuity of scientists and, and interesting to speculate about how it will be equally ingenious in the years to come.

One hopes. But good. So let's get down to brass hacks about the genes and how they work. I mean, so we assume we know the basic story, but an important part of the story that you tell in some assembly required is that, of course, we have genes. That is to say, we have segments of our DNA that code for proteins, and then the proteins go and do useful things in our body. But then there's other parts of the DNA that are regulating when the genes are switched on and switched off. And there's also junk DNA. And how does all that fit together?

And how does it play into this story of major transitions? Okay. So just to set the stage, right? So, you know, DNA sits in the nucleus of all of ourselves, right? And in each cell, there's about six feet. So if you have a strand of DNA, it's about if you were to unwind it, it's about six feet long, you know, sitting inside the nucleus. So it's packed super tightly. Think about that.

You know, you have about 4 trillion cells. So, you know, if you put all our DNA end-to-end, you know, of all our cells stretched it out and laid it end-to-end, it would go almost to Pluto, right? So that's just, think about just how much genetic material is in our bodies and how tightly packed it is in each cell. It's kind of mind-blowing. Now, when we think of genes, when we think of DNA, right, the DNA is a sequence of basis, right? So it's a gene sequence.

So it's in a double helix that it's packed really tightly. You know, so there's a part of the DNA. that contains the information to make a protein, right? That's the protein coding part. But there's a whole other sex, parts of this, that does other things, some of which we don't even, we're still grappling with.

But to give you a little perspective, the gene part of our genome, right? That part that makes proteins is only 2% of our genome. Yeah. Well, so genes only make up about 2% of our genome. So the protein coding part, the part that contains the information to make the proteins, is just a tiny fraction of the genome.

The rest of it kind of controls the activity of those things. Is that completely true, or is it also true that some of it is just kind of wasted space? It could be. Yeah, it could be wasted space, or it could be space we don't know its function yet. See, a lot of the activity of DNA is related to its dynamism, how it opens and closes, forms, loops, and on itself. And so those spacer regions could have lots of importance in terms of the overall geometry. of the DNA, but the individual sequence might not matter as much. Who knows?

Okay, that's interesting. But there's still a bit of a mystery. Still quite a mystery for us. And boy, there's a lot of ink spilled debates around that, too. So, but, you know, you think about it this way. If you take us, the cells in our body pretty much all have the same DNA inside them. What's different is they're making different proteins. So the cells in our, and the retina of our eye compared to the cells in the skin of our

fingertip, you know, they have the same DNA inside. them. But the DNA in the retina cells is making proteins that builds and keeps a retina functioning. The cells inside the tip of our finger, you know, they have the same DNA, but the genes that are active are the ones making the skin tissues, right? Proteins that make skin, give skin tissue its properties. So what's different here is which genes are turned on and off in each kind of cell, in each kind of tissue. So it's not the DNA per se that's utterly different. It's what's controlling their activity. So people have really, since the, oh, I'd say the mid-late 80s, really focused on that.

What are these genetic switches? What controls whether a gene is turned on and off? And, you know, once we know that, is that a big player in evolutionary change? And it turns out, yes, yes, and yes. That's the understanding of these switches is so important, not only to understand what makes tissues different in health and disease, but also to understand evolution to say, well, you know, it's not like, you have a new protein-coding gene. If you have the same gene, it's just you're turning on and off in different places and different times in development.

So it all comes back to development and what these genes are doing in development. And if you're turning on genes and turning them off in different times and places, you can make really big changes, right? I mean, is it possible to explain to us at the molecular biology level how the information encoded in one side of the DNA actually does turn on and off the other sets of DNA? Yeah. So what you have is a bunch of,

so you have the gene, the protein coding gene, and lying next to it is usually a little sequence that when something attaches to that sequence, some very important things attach to that sequence, it'll turn the gene on or turn it off, depending on what the nature of that little section is. So it all comes down to sort of molecular keys

that come in, so basically one part of the genome might fold over, to touch that switch. And if it does that, it activates the gene. So there are lots of little triggers that would control these things. But you have to think about this as a very dynamic chemical landscape, where chemicals are being, you know, proteins and other factors are being made. And as they do that, they're attaching to these different sort of switch sequences in the genome,

which then control the activity of the gene. So it's three-dimensional structure. You have the, you have the, you have the genome opening. and closing. So when the genome is closed, it's not making proteins. So it'll open up in areas where proteins will make. So first it has to open up. So there's that dynamism of the genome. Then certain sections have to come in and touch these switches, actually connect to them to activate the genes. So there's a whole sort of Rube Goldberg kind of set of activities that have to happen for a gene to turn on. Does the three-dimensional structure differ from one kind of cell to the other?

It can. Yeah, very much so. And so, in fact, that's a very active field of research right now in molecular biology is understanding this three-dimensional changes. And it's really come, it's really gotten very big as now we can see the genome. We can begin to map it. We begin to see it at work. And it's, you know, what surprises everybody is just how utterly dynamic it is and how very important this three-dimensional structure really is. And there's lots of mysteries here.

We don't, there's a lot. We don't understand. And because it's, it's filled with puzzles. But one thing we do understand is just, you know, how these changes. changes can affect evolution. And that is pretty clear. That is if you change a switch, you're going to change the ability to make a new, you'll be able to make some new things in evolution, a new tissue, new protein, and so forth. And that fits in with the connection with development, because obviously development is all about deciding which kind of cell I'm going to be and where I'm going to fit in and therefore what parts of my DNA are going to be useful. That's right. And, you know, it's basically, if you think about, you know, the genome of an organism, is basically forming a recipe for development.

You know, you're changing the ingredients. You can change the genes. You can change the process, which is these switches. And what you do is subtle changes to these things. In the embryo can have large consequences, you know, to anatomy, to evolutionary history, just like we saw with the salamanders. And so what we can now do is look at that at the genetic level. So does this help explain some features of major transitions?

I mean, does it make it easier to understand how major transitions can happen once we understand? this picture of certain coding areas of the DNA and other regulatory or expressive regions of the DNA? Oh, very much so. It can show, for instance, and it's kind of getting back to one of the themes we talked about earlier with the fossil record, is that you really don't have to often event whole new things to have great transitions happen. A lot of great transitions might not involve as much new genes as it would involve using old genes in new ways. So using genes that exist, but you're changing when and where they're. they're active. So again, it's like kind of the, you know, the raw material for these transitions exist before the transitions themselves. You have the genes, just using them in new ways. That's

part of it. There are cases where lots of new genes come about. But using old genes in new ways turns out to be a very profound part of these great transitions. We see that over and over again. The other thing that is getting renewed attention, which is really fascinating, and we see this over and over again. We see this in the, you know, the origin of new biological inventions, but we also see it in the, you know, the human technological realm is that one thing that's very common is multiples. That is, you'll see the same, called evolutionary invention appear independently in different species at the same time. That is the same solution to a problem appears independently, you know, in different creatures that are not directly related to one another. So it means it's

happened separately. And one of the reasons why that may happen is, is if organisms, if creatures have the same set of genes functioning in the same ways, it makes similar outcomes more likely, right? So this notion that you can have parallel evolution or independent evolution of the same structure is something that's gaining renewed intention from the molecular realm, because if organisms have similar genes and they're using those genes in similar ways, then they might produce the same kinds of mutations independently that natural selection can work on. Because it's not random.

some sort of common starting point. They're not just, like you say, not just randomly choosing crazy things. That's right. If you have a recipe to build, make cupcakes, you know, there's only certain ways you can change that recipe,

right, and have it still be recognizably cupcakes. So, yeah, and you'll hit upon the same, you know, if different people are making cupcakes through the same recipe and playing with in different ways,

they may come up with the same kind of cupcakes independently. So this helps explain certain examples of conversion evolution? It does, very much so. Conversion evolution can happen for lots of reasons. So first is, you know, and a very common reason is, you know, common adaptive solution.

You know, if creatures are going to fly, they're going to eat some sort of wing, right? And, you know, you see that over and over again. And you see, you know, white color patterns appearing independently in polar animals, that kind of stuff. But the other reason why these sorts of that pattern may happen is, again, common recipes, common genes, that sort of, common recipes to build bodies, common genes, that sort of thing. And does it help explain this puzzle that's always there in? evolution, what I think of as the statistical mechanics of mutations. Like, most mutations are presumably really bad. Yeah, most are not so good. But, you know, it doesn't take many to, many beneficial ones to really take off, you know, so a beneficial mutation can gain traction

very, very readily. But, you know, we talk about mutation being random. It's really not random, right? It's, you know, it's only random with respect to, like, predicting the future. I mean, it's like, You know, just because a creature may need to walk on land in 100 million years doesn't mean it's going to come up with mutations to do that. Sure. You know, so it's non-random with respect to the needs of the organism in the future, right? But, I mean, it's random with respect to the, excuse me, you know, it's random with respect to that. But it's not random with respect to all, everything else, you know. Certain mutations are more common than others based on what happens in the genome.

Certain mutations are more likely to be beneficial than others based on what happens in the genome and in development. You know, so yeah, so when we talk about random, you have to be very specific about it. It's random respect to predicting the future. It's not random. Well, you talk in the book about the idea of hopeful monsters and how they kind of got you in trouble as a graduate student. I got me in trouble with Ernst Meyer in a very big way. Yeah, I really, so I used to have tea. So one of the great gigs of my graduate student life was, I don't know how this happened. I was not a great graduate student. But Meyer took a shine to me. Ernst Myers is great eminence. and the new synthesis of evolutionary biology.

He was huge eminence. He was about in his mid-80s at the time. It was very old and had a lot of history. And he loved history of science and philosophy of science. And he was there during one of the pivotal times in our field. And for some reason, took a shine to me. And he used to invite me for Thursday, up into his office on the fifth floor

of the Museum of Comparative Zoology at Harvard. And I made the pilgrimage there every Thursday. And I was up in the bird collection. It smelled like mothballs. And it was this old creaky floors and mire. would, you know, sit in his chair and just wax about great people in the field. And he always encouraged me to come with a book, a paper, a question, to stimulate it. So I came, I came one day with this book called The Material Basis of Evolution, which is a recent reprint. It

had an introduction by Steve Gould that just came out like, you know, a couple weeks before, a month before. And I brought it up to Myers. See, look at this new thing. What do you think of Gould's preface? And he just turned beat red and shut. me this glare like, kid, I'm going to eviscerate you. And he went to his filing cabinet, came back with his paper. He says, I wrote animal species and evolution in response to page 95 of this piece of crap. And he threw it down on me, this yellowed reprint by Goldschmidt, which laid out the theory that you can have major evolutionary transitions in one step, in one mutation, so-called

macro mutations. Now, I knew Goldschman was a bit of a whipping boy at the time, but I wanted to do. to talk to Meyer about, you know, what he thought about it, was, you know, that kind of thing. Oh, boy, yeah, I was just, it was something else. So Gullschman's idea, the one that got me so in trouble with Meyer. Oh, by the way, the T's did continue. I think they, it was a famously contentious place, Harvard Evolutionary Biology, right? Oh, I'm sorry? Harvard Evolutionary Biology seems like a famously contentious place. There were big personalities. It was, yeah, at the time, because you had E. E.O. Wilson and Steve Gould at the time, Richard Lewinton, Meyer, yeah, so I had to navigate that a little bit. Anyway, so I did so pretty much unscathed. Anyway, so the idea was that you, you know, Golchman proposed. He studied development, right?

And he studied genes. He said, look, subtle changes in development can yield big effects. So, hey, the first bird hatched out of a reptile egg. He said basically one mutation, you know, one cent of mutations, you got a bird out of a reptile. And, you know, that was not well received for good reason. lot of reasons why that theory was bound to fail. But it's, it's reappeared in different ways over the years. But there's really is not, not a very viable theory, despite the fact that, you know, you can find mutations that will do big things to the animal. It just turns out that those

big mutations are almost exclusively, you know, lethal. It's really the small mutations that are most likely to be beneficial. So it's the accumulation of these. Owning a home is full of surprises. Some wonderful, some? Not so much. And when something breaks, it can feel like the whole day unravels. That's why homeserv exists. For as little as $4.99 a month, you'll always have someone to call.

A trusted professional ready to help. Bringing peace of mind to $4.5 million homeowners nationwide. For plans starting at just $4.99 a month, go to homeserve.com. That's homeserv.com. Not available everywhere. Most plans range between $4.99 to $11.99 a month your first year. Terms apply on covered repairs. So that's sorry, that is the current way of thinking that, in fact, it is the accumulation of tiny things that is much more driving the engine of evolution. Yeah, yeah. But that accumulation can happen pretty quickly, right, over geological time scales. It does, you know, it's, you know, the geological time scales I deal with are in the millions, hundreds of thousands to millions to tens of millions of years. Yeah. You know, we're talking about these accumulation of these mutations can happen much, much, much, much faster than that, particularly in knowing ways the genome can change. Well, it's going to have. Well, it's going to

ask this about the issue of missing links when you've begun such a transition. There's no teleology. You're not aiming for some target, but once you've sort of been able to enter a slightly different ecological niche, is it true that then the rate of evolution is faster for species like you than those that are happily in their equilibrium? And therefore, there are fewer records of those in the fossils? Oh, that's an interesting point. So there are cases where creatures enter a new zone, like ecological zone, and the evolutionary rate takes off. But there are other cases where it's a delayed fuse, where something happens, and that diversification, you know, the explosive diversification, doesn't happen until much later. And we really don't know why that

happens. That's a bit of a puzzle, you know, why you might have that. Yeah. So that's still very much an open question. Okay. I always like to, you know, give the undergrads and graduate students out there in the audience problems to work on. So that sounds, it's always good to find the open questions. We got lots of those. Yeah, exactly. That's what makes it fun, definitely. Well, and so there's also, you already mentioned this, I think, very briefly, but let's link it back in here now that we're talking about the transitions at the molecular level,

the idea of genes jumping from one animal to another and being borrowed, right? Like you tell the stories of how viruses, virus genes got embedded in other people's genes. I think this is something, obviously, that is not part of the classic story of molecular biology and evolution. No, it's amazing. So, like, when you look at a, like, a human genome sequence, we've sequenced, you know, we can sequence genomes now pretty quickly, right? When you look at a gene sequence, what you find is in humans, about almost 10%, about 8% of our genome, of our entire genome, are defunct viruses. Viruses that viral sequences that no longer function, you know, but they're there. It's like a fossil graveyard, you know, a graveyard of ancient viruses that attacked our genome, became part of our genome, but then got knocked out.

Every time I talk to a biologist, it's very important that they creep out the audience at some point or another. That's my goal here. I mean, my goal is to creep everybody out. And, you know, think about it gets even creepier still when you think that, okay, only 2% of our genomes are our genes, you know, but 8% are like the fun viruses. Yeah. But there's also something else that's really amazing about these. So viruses are, as we know, as is very relevant in today's world, viruses are, we live in a balance with viruses, right? They're continually infecting us. And our internal mechanisms, whether it's our immune system or our genome, are trying to knock them out, or are trying to disable them. But there's something else that's happening as well. And this is something that's pretty new. And it begins with, there's a researcher where I talk about in the book, Jason Shepard at the University of Utah. He's, you know, he's a neurobiology. He's not interested in viruses. He was an MD, though. He studied his microbiology. But he's interested in memory, you know, and his research in memory led him to a gene called ARC, A-R-C, because ARC is a gene

that is involved in memory and people. Mutations in that aren't associated with dementia, schizophrenia. Mutations in ARC and mice mean that they lose their memories. They can't, they can do a maze, but the next day they forget their solution. And so he's studying ARC. That's his thing, right? Because he cares about neurogenital diseases and memory. And he's studying Arc, and he's studying, when you study a gene, you're going to study its protein.

So he looks at the protein that ARC made. And he pops in a microscope after some effort. It turns out he saw these spheres, these spirials. And he's like, looking at him thinking, I've seen these spirials before. In his microbiology class in medical school, the capsules that look like the virus, HIV, the virus that causes AIDS. They're like, wait a minute, this looks more like a virus than a memory protein. So he runs down to the next building to talk to people, AIDS experts, doesn't tell them what is on the slide.

It says, identify this for me. These AIDS experts look at the HIV experts, look at the slide, and they say, oh, that's HIV, the virus causes AIDS. This is, nope, it's arc. The memory gene in people. They're like, what? Do not trust biologists bearing gifts. Yeah. So what happens is what Jason Shepard showed in his lab and some others as well is that what ARC is, is this an ancient virus that invaded a distant ancestor of people.

And that virus, instead of being knocked out by the genome, it was domesticated. It was repurposed. It was like, sorry, you got a new job. You're no longer going to infect us. You're going to make a protein that's going to be used in memory. And what's relevant here is that capsule that is made by a new job. HIV and ARC helps the information, the genetic, that capsules made to protect the genetic information of the virus as it goes from cell to cell. So it makes HIV very effective in going from cell to

cell. But that's exactly what makes the ARC gene effective in making memories. It goes from neuron and neuron. So this virus was put to work, was repurposed, if you will, by our distant ant, the genome of our distant ancestors, just how we don't know, but it was, to play a role in memory. And we're finding that in all kinds of other genes, too, and genes that make the placenta. They, the proteins that make the placenta, some of those genes were originally viruses that invaded the genome. It's all repurposing. That's all evolution ever does. It's repurpose. Yeah. It's either take something from something else and repurpose it or repurpose your own genome. And, you know, it's mergers and acquisitions. It's claiming things as well as your own. Yeah. And so it's a real wild

world. But, you know, these viruses are not only threats, but they're sources of genetic information, genetic novelty. There are sources of new genetic stuff that occasionally have made a very big difference in our evolutionary history. And that's one thing that within the last decade has become under much clearer focus and it's really remarkable.

And we should probably distinguish because probably many people have heard the story that you relate in the book about Lynn Margulis and the mitochondria and so forth. And that's sort of we absorbed little tiny organisms and made them part of our cells. but mitochondria have separate DNA. This is what we're talking about now

is actually sticking segments of virus DNA into our DNA strands, right? Yeah, so what a virus does, right? There are lots of different kinds of viruses. There's many different ways that this happens, but typically a virus will enter, and then it goes into the genome of its host and then commandeers the genome to make more copies of itself.

It's like the ultimate parasite, right? It goes in there, makes copies of itself, takes it over the machinery, makes more copies of itself, and there it goes. So what happens, sometimes the host can take over the virus or knock off the virus, but also take it over to do new things. And that's what we're seeing in some of these cases. So the viruses can be the source of genetic novelty, right? New stuff as well. Yeah. Yeah. Yeah, it's pretty amazing. And I don't know how much you followed the controversies over at what point do we stop calling this Darwinian evolution. I mean, obviously, you know, Darwin said a lot of true things. And then there was this new synthesis, with genetics and so forth, but the idea that we simply, you know, do sexual reproduction and some of our DNA base pairs get mutated, but otherwise we just hand them on,

is way oversimplified, right? And so at what point do we call it a new theory versus just little tweaks on the old theory? Yeah, it's hard to say. I mean, you think about what Darwin did, though. Darwin, the largest species, the first edition was 1859, right? There was no knowledge of genetics whatsoever. Okay, we didn't know anything. Mendelden come to much later, let alone a knowledge of DNA.

Yet that theory he proposed before genetics kind of didn't make sense under the kind of inheritance that they thought then. So, in fact, some of the most trenchant criticisms of Darwin were about that, you know, that and without a, there was no knowledge of genetics with no knowledge of, you know, heredity. It was really hard to think about how these changes could be sustained over time, though he did use artificial selection, artificial breeding experiments as well in his argument. But, you know, it's a good point. You know, we have moved far beyond, but we're staying very much in the center of Darwin.

Natural selection is still the major mechanism of evolution. Common descent is still the major pattern we see in the history of life, albeit with some, you know, exceptions where you have information being traded among species. You know, when we talk about Darwin, we're really talking about not just a body of a theory, but a profound shift. The Darwinian revolution was a profound shift in the way we see the natural world, how it came about, and our relationship to it. So when we think about, you know, certain Darwinian biology, I kind of refer to it in those ways in terms of, you know, the fruits of the Darwinian revolution. Yeah, yes and no, we're still using some of Darwin's ideas. I mean, one of the main ideas in the book is actually a Darwinian one, the idea of repurposing, the idea that, that structures arise in one form originally,

and then they change function later on. But, you know, it's just amazing to me. I read the book, I did a deep dive back into several of the editions of Darwin, different editions, in preparation for writing, some assembly required. And I was struck by so many things. I was struck by what a great way he was able to marshal evidence, how he used it, what a great writer he was.

You know, not only in producing evidence, but some of his prose is just really beautiful. I just would sit there and read it over and over again. It was just amazing stuff. He just what a remarkably talented human being. Yeah, we're lucky because of that, right? Because not all scientists are like that, but he did have the ideas and was able to convey them

in an especially compelling poetic way. So that's nice. Yeah, so beautiful. It really is. At every level, at the intellectual level, as well as the aesthetic one. Yeah. All right, so I think that we're able to get some payoff here.

So all this understanding of genes and expression and regulation and so forth, tell us how this experience. explains how fish can develop hands. Well, I mean, my lab works on that. And, you know, in the summer we go out to find fossils and the rest of the year we're working on the DNA of extant fish. So, you know, working on mice, people were able to identify a series of genes and regulatory elements,

elements that control the activity of those genes, that are deeply involved in making wrists and fingers, and mice and people and everything that has wrists and fingers, right? And you can identify those genes. And, you know, they showed, for instance, that if you, say, make a mouse lacking these genes, the mouse has a humorous, a radius and all no, but no wrist and digits. If you mark the cells that, you know, that where these genes are active, they're in the wrists and the digits. So these genes are wrist and digit genes. They're necessary for the wrist and digit. Not necessarily sufficient. There are probably other ones as well,

but they're necessary. So my lab as well as a bunch of others have asked the question, are these genes present in fish? The answer is yes, we've known that for a while. And if so, are these genes involved in fish fin development? And again, if so, what are they doing in fish fins? So that's what we've been looking at. Well, it turns out to make a very long story short, this is like a 10-year research program of my lab,

longer than Tectolic, actually, the search for Ticotolic. That was six years, this was 10. But the central idea is, that many of the genes that make the wrists and digits of mice and people and birds and so forth are precedent fish. And they're making a terminal strip of tissue in those fins. And that terminal strip of tissue gives rise to the fin rays. Those, you know, the spicules of bone that you see, like if you look at a trout, when you look at its fins, it looks clear in the terminal end of the fin with little rays inside.

They're little bony rods. It makes those rods. And so what's remarkable here is that there is a common toolkit to make appendages as different as people, mice, and fish, fins, and limbs, that those genes are there, that they're active. And that in all species, they're active in making the terminal end of the fin. What's different is there's a switch in fish that turns those cells where those genes are active into fin rays, whereas in us and, mice and others, it makes, it makes, it makes fingers and toes. So what we're able to see is that there's a common history, genetic history of limbs and fins, and that the differences among them aren't as much in, you know, entirely new genes, but it's using, in using those genes in new

ways and modifying their activity in different ways. So there's a case where molecular biology has given us insights that we might not have had otherwise. Because if I was just looking at anatomy, I would never compare fingers and toes with the thin rays of fish. But there's a clear-cut developmental connection between them. And so now what we're doing in some other labs are looking at, okay, well, what controls whether you have a finger or a thin ray? You know, what are the molecular controls that control how you make those different

kinds of tissues? So as we open the whole thing is it's, you know, when you have answers like we had with this research. Now we can ask a whole new kinds of powerful, more precise questions. So these answers now set us up for a whole new set of experiments, which we're doing now. And do you go in, is this by going in and zapping

some of the genes to kill them off or keep them going longer and seeing what kind of organism results? Yeah, so what we'll do is we could take the genes from a mouse and put them in a fish and it can see what they do. We could take the fish genes and put them

in a mouse and see what they do in that in that new environment. It turns out they function very well. I could take a shark gene from the fin and put it in a mouse some of these genes from a shark and put them into a mouse and it does perfectly fine. Likewise, the mouse one in the shark. So we can make these swaps. We can also knock these genes out. We can use CRISPR cast genome editing, you know, go in there and just knock these genes out and delete them. We can add factors as well. So yeah, it's a real, you know, House of Horrors here. We can do it all. But what it shows is quite literally that, you know, that there is a deep connection among creatures. You know, nothing is more, I still find it amazing, that we could take a fish gene and put it in a mouse and it functions just fine, you know, in the limb of a mouse.

You know, where it is in a fish, it works in its fin. That in a nutshell just shows you just the deep connections among, you know, all life on our planet. Are you a fan of the sci-fi channels TV show Shark to Puss? No, no, I haven't seen it yet. I think that should be your next project. I do so. I'm surprised they didn't call me to consult. Well, I mean, let's, you know, we're at the end of the podcast here.

So now we can let our hair down and speculate a little bit. We've learned a lot about how major transitions happen in real evolution. You're opening, I don't want to call it Pandora's Box, but at least a whole door onto a new landscape of things where we can make major evolutions in our labs. Like, is this going to be a frontier over the next hundred years where we're, I mean, not just figuring out how evolution happened, but designing organisms for human purposes. Oh, I mean, I think, you know, it's already happening, right? I mean, you have people growing organs and dishes, you know, tissue, tissue engineering for clinical purposes as well. You know, we already have people who use computation and a knowledge of evolutionary history to resurrect proteins that were present 400 million years ago. and test their activity.

No, we can reconstruct ancestors, at least at the biochemical level. We can modify development at the embryological and developmental level, and genetic level as well. And we can begin to mimic in certain stages of evolution. That sometimes is helpful, sometimes it's not. But we're definitely in this brave new world where we can manipulate things as well. The big game changer has been obviously genome editing, that CRISPR cache gene editing, which applies to so many species.

It's remarkably effective, but it's also remarkably cheap. You know, so a lot of issues, which is important when you run a big level. And that, yeah, and that's been a huge game changer for us. I mean, I have a colleague here at Chicago, Joe Thornton, who is literally resurrecting ancient proteins to understand how enzymes originally came about. And he uses, you know, knowledge of evolutionary history and computation to make predictions about what those proteins look like, and then he makes them in the lab. test their activity.

And we can tweak genes right now to test, can we make a limb bone in a fish fin? I have a colleague from Harvard who did just that with a mutant he found and showed that fish fins have the ability to make limb-like bones.

So really remarkable stuff. It's definitely a brave new world. Yeah, so the answer is yes, we will be seeing, I mean, it's just the beginning of all this and people talk about regulating it and so forth, but my rough feeling is that once you can do something, someone out there is going to do it. And so remixing all sorts of organisms and their organs

is going to be a major frontier. I think so. And what will drive it obviously would be clinical, you know, making new kinds of tissues that can help in, you know, regeneration. Regeneration is a big thing too. Sure. Being able to rebuild organs too. And that's people are pushing the limits of that as well.

Well, okay. So for the very last question, let's return a little bit, back to reality. We talked about how fins can turn into hands and so forth, but the other obvious question is human beings, right? We're very similar to other primates, but we do have these big brains. I recently saw a claim, which then I think I saw people arguing against, but the claim was that there are mental capacities, cognitive capacities, that chimpanzees are much better at than we human beings, you know, short-term memory kinds of tasks. And the claim was that we have, I don't say intentionally, but we have sacrificed that part of our cognitive capacities in order to develop

language and linguistic capacities. Is this kind of trade-off a big part of what turns other primates into we smart and sexy human beings? I don't know the answer to that, but trade-offs are a very huge part of, of huge. history, right? There's tradeoffs in terms of the structure of our brain. There's tradeoffs in terms of the structure of our general system, our ability to walk. The tradeoffs of just being human are huge because there are costs to being human. We suffer certain kinds of conditions that are not seen in other creatures. Our ability to talk, for instance, I'm just shifting it from the cognitive piece because I know less about that, honestly. But our ability to talk comes

it a huge tradeoff. So it wouldn't surprise me that cognitive issues do as well. So for instance, you know, we are the only animals that suffer a certain particular kind of dangerous sleep apnea. And the reason for that is we have a very flexible back of our throat and a set of neural circuits

that play a huge role in our ability to make sounds. So our ability to make sounds for language comes at a giant cost because it sets us up for certain kinds of sleep apnea which can be quite dangerous. But that's true for almost every part of the human body. I mean, whether it's walking on two legs, whether it's having huge brains that consume an enormous amount of energy, whether it's having cognitive capacities

to make language that are tradeoffs from other kinds of cognitive capacities, which we might have had. You know, tradeoffs are a part of being an extreme organism like we are. We're highly optimized in certain ways. And that optimization comes at a cost, you know, because of the inherent nature of tradeoffs. I mean, I guess I already said this is the last question, so I lied. But I just had a podcast with Martin Rees where we talked a little bit about the prospects for post-humanity and how, you know, in different environments and so forth, we might evolve in different ways, like people living on Mars might have different skeletal structures or something like that. Is it completely crazy for an evolutionary biologist to look at human beings and say,

well, here are things we could improve? Here are things that we could intentionally change that would make us better, like, you know, get rid of back. cakes or something like that? Oh, yeah, definitely. I mean, there's, I mean, in fact, our relationship to the microbial world, we can change. You know, when you think about, we're just beginning to come to grips with our relationship to the microbial world. And that relationship can sometimes hurt us, but oftentimes, most of the times, it's essential

for our lives. And that's something that, you know, as we look forward, that's something that is going to be incredibly important to think about. But no, I mean, you can look at all, any part of our body and say, you know, well, geez, that's something that needs to change going forward. But a lot depends on the operative environment that we find ourselves living in. So the environment today, yeah, you could say certainly that there are certain aspects of our bodies that in this modern environment that we're kind of disconnected from.

You know, we have an evolutionary history in one environment, yet, you know, many of us are living in, you know, in built environments now that are very different. And we have a sedentary lifestyle. So our whole metabolism is sort of ill-equipped. You know, we evolved from a highly active, you know, ancestors, and most of us are kind of relatively sedentary. Less active. You are.

When you think about the leading cause of death, you know, cardiovascular disease, cancers and so forth, these are all parts of the trade-off of being human and living in our modern world, right? And so I could think of a whole host of things that we need to change. You know, we are susceptible to all kinds of cancers that are a product of living in our modern world. of living, you know, after 50. And so, yeah, I could give you a list of many things to change based on where we're living now.

And I can give you even a longer list if, you know, you're telling me we're going to be living in bases on Mars or terraforming somewhere or whatever. Well, good. It's good to know that, you know, we're members of the last generation of purely organic human beings. Well, I'm part iPhone, actually. I'm actually merged with the device. We were born organic. We've deteriorated over time.

All right. Neil Schuven. That was a fascinating conversation. Thanks for being on the podcast. Thanks for having me. Appreciate it. Deadlines move. Plans change. And sometimes opportunities pop up out of nowhere. When you need branded gear fast, For Imprint is ready to deliver. Four Imprint offers hundreds of promotional products in their 24-hour category.

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