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Ep #3 Transcript | Sean B. Carroll: Chance, Evolution, and the Nature of Innovation

Updated: Sep 6, 2021

Full episode transcript below. Beware of typos!

Nick Jikomes 0:28

Welcome to the Mind & Matter podcast. I'm your host, Nick Jikomes. And today I'm speaking with Dr. Sean B. Carroll. Sean is an award winning evolutionary biologist, writer, educator, and film producer. He is currently Vice President for science education at the Howard Hughes Medical Institute, where he's also head of the tangled bank film studios. Sean is also Chair of the biology department at the University of Maryland, where he has an active research lab, and the author of several popular science books. Among his many, many awards and honors, Shawn is a member of the National Academy of Sciences, and his documentary films have earned two Emmys. his new book, which was just published in late 2020, is a series of fortunate events, chance in the making of the planet life. And you,

Sean and I talked about all all kinds of stuff. And we touched on everything from his remarkable career to his writing process. We talked about dinosaurs and snake venom. And we even talked about COVID-19 the evolution of viruses and how some of the new Coronavirus vaccines actually work. If you find the content in this episode, helpful or interesting, please do consider liking, sharing or subscribing. And with that, here is my conversation with Dr. Sean B. Carroll.

Sean Carroll. Thank you for joining us. Thanks for having me, Nick. It's been a long time for for the listeners who don't know, which is probably everyone. You're actually my scientific grandfather, I guess. I got my start in science in your lab.

Sean B. Carroll 2:27

I remember when you first came in, you were one of perhaps the only incoming freshmen I ever experienced to read. And you'd have to tell me how many of my books you've already read. I thought, Oh, my God, I can't get my graduate students to read these books. here's, here's here's somebody who hasn't even taken his first freshman class. And he's ready to rock and roll.

Nick Jikomes 2:45

Yeah, it was, it was your first book. And we can we can get to that I definitely want to talk about that book. But you're really interesting, because you're a biologist, but you're not just a biologist, you do a number of things. And so how about if you meet someone at a cocktail party, they have no idea who you are. And they say, so Shawn, what do you do for a living? What's the first thing that you say?

Sean B. Carroll 3:08

Oh, I tell them I'm a biologist, I think the science identity is is for most it's kind of everything revolves from that. And I've been really fortunate in the course of my career to have periods where I focused exclusively, exclusively on what I'll say is discovery science, when you were in my lab, I was able to branch into writing sort of somewhat at the same time. And then more recently into filmmaking or being part of a whole filmmaking enterprise. And then areas of philanthropy and all this other sort of stuff maybe we can get into. But it all started with a scientific lens, a scientific perspective, and both the desire and the opportunity to share that process, the substance of those discoveries, or the journey of those discoveries, and sort of the scientific worldview, with all sorts of audiences, and I really enjoy it. And it's just sort of diversified into lots of different media, whether that's doing, you know, stand up talks and live audiences or books or films.

Nick Jikomes 4:17

So, as a biologist, what what do you study? And are you still running a lab right now? Yeah,

Sean B. Carroll 4:23

so I have a lab at the University of Maryland. So for the last good amount of time is spent exclusively focused on evolutionary questions. And the big question my lab is interested in is where to new things come from. And that's also something you bit off in your undergraduate work. So the focus of study has changed because you know, model you attack different models use different models that you think might give you insights into certain questions. And so in the early days, I was really looking at new physical patterns.

For example, body parts and body patterns, were the new things come from there, more recently wanting to know where new for example, biochemical functions come from, and particularly using snake venom as a model. So, Venom's have evolved many times in the animal kingdom, fundamental question is, well, where the heck did all this stuff come from? And, you know, to what degree is this all new stuff or old stuff that's been repurposed. And fortunately, we're living in a time where those kinds of questions we can get down to the brass tacks of, of how things work. So, when you study evolution, let's just take the venom example, how the hell do you even study something like that? What do you guys do? Well, you start with with the stuff you're interested in. So let's take rattlesnakes, we chose rattlesnakes, because we knew we're going to have access to material and they're better recent fair, a fair amount of study of them. And,

you know, venom is this cocktail of proteins that the snake injects into its prey for accidental human victim. And these things, do a bunch of stuff that essentially take the prey down, either kill it quickly, or at least disable it so it can be consumed. And that it because it's a cocktail of stuff, you'd ask, Well, how do we get all this stuff? It couldn't possibly get all this stuff overnight? So it somehow has been assembled over time. So how do you figure out how this was assembled? And where did it come from? And when you say where did it come from proteins are encoded in DNA. And so that means DNA is really the crucial record of invention. And what you want to do is study animals that have and make Venom's like rattlesnakes, and compare them to things that don't have those things and say, Alright, here's a certain toxin gene, where the heck might have come from, and you get clues from, for example, the, if you if you sort of parachute into the DNA where that toxin gene is, and you look around, you might find adjacent genes that are present and all sorts of non toxic animals. And that starts to give you a clue of where that gene came from. And then you look at that gene in detail and say, Well, does that look like an old gene that's just being used in a new way? Or has the gene been modified in some ways to maybe, you know, sort of weaponize it? So these are the kinds of questions or asking, so it's its comparative approach. And then it's, it's a deep dive into sort of the DNA record of evolution to say, Where did this arsenal of toxins come from?

Nick Jikomes 7:30

Well, so in the case of rattlesnake venom, what are these proteins do they do they look like other proteins that do something more

Sean B. Carroll 7:38

basic? Absolutely. And they come from, essentially household housekeeping proteins that all of us have very familiar stuff from a lot of four legged animals and fish have. So for example, rattlesnakes to big classes of toxins, they have these toxins that are certain rattlesnakes have toxins that are neurotoxic, and they can drop you pretty quickly, respiratory arrest. And those came from a class of enzymes called phospho, lipase, a tos, and they've been modified a bit. But nonetheless, they're totally recognizable as members of that family. And there's another group of proteins, these are enzymes called metalla proteinases, it just means they to a protein, and they, they use a calcium or zinc is a in doing that, and we have tons of them. Lots of animals have tons of them. And just one of those was co opted and modified A long time ago in the lineage that gave rise to rattlesnakes and their close relatives, the Vipers and some of their more distant relatives. And the snakes have just gone crazy with this. So one gene that you can see in all sorts of four legged animals has been expanded to a battery of 30 genes in the western diamondback rattlesnake. Bam, bam, bam, bam, bam, bam, bam, right along the chromosome, you see it and that that Arsenal, that battery of toxin genes is telling you something that something has been specifically expanded in this lineage that is obviously important to the way it lives. So those are the kind of forensic clues that we can discover in DNA that tell us where the toxin genes came from, and how they've been modified. Now, we didn't know any of this six or eight years ago, because we were the first to look in the genomes and, and and ferret some of this out. But But nonetheless, we've been surprised lots of times it First of all, it's gratifying to be able to trace the origin of things. That's not something that evolutionary biologists have been able to do until fairly recently. But also the stakes just they do some weird things. They've got their snakes that their populations have, for example, rattlesnakes in the southwest, where some individuals are neurotoxic, and some individuals are hemorrhagic and there's really surprising levels of genetic variation between individuals. We know that ancestors of most rattlesnakes were neurotoxic. A bunch of species are not. And you think, Well, once you invented a neurotoxin, why would you ever get rid of it, but that cooling what they've done? So, as has always happened throughout my career, you know, you get surprised because it turns out, the real story is opposite or upside down to what you expected that you would think when you invented a potent toxin, you'd never get rid of it. You'd think that if it was a really potent toxin, every member of the population would have it. It's not the case. So we're enjoying kind of the natural history of these snakes, at the same time understanding these kind of general evolutionary questions that we're trying to pursue to the real satisfactory resolution.

Nick Jikomes 10:37

Where, where do you get the raw material? Yeah,

Sean B. Carroll 10:42

so we have collaborators in Texas woman named elder Sanchez, runs a big center there that houses all the snakes, and it's a federally funded center that houses all sorts of poisonous snakes, and they've hosted my lab group, multiple times, we also get stuff, you know, through FedEx, I can tell you that when I moved my lab from the University of Wisconsin to the University of Maryland, my Maryland hosts were quite happy to hear that I was not bringing in tons of rattlesnakes that they would have to house because you can imagine on college campus that bad things could happen if you had a basement full of rattlesnakes, somewhere. So on the material is pretty straightforward to get a little bit of venom goes a long way, a little bit of blood for DNA goes a long way. So yeah, and And now some of those tissues, we can culture. So we don't actually need to take things from from living snakes. So it's sort of becoming a little, you know, it's not quite fruit flies in terms of ease of certainly ease of housing or anything like that. But in terms of experiments, and then it kind of studies we do, it's opened up, you know, I should also mention, you know, people may not care at all about snake venom, although they're pretty interesting model. But, you know, think of parallels, for example, the invention of milk in mammals or the invention of antifreeze in certain animals. These are comparable stories of well, where did new things come from that sort of open up lifestyles? So that's the general question that we're trying to understand is, you know, how do things get invented that then sort of blast open new ways of living and rattlesnakes themselves have radiated fairly recently to a really good number of species and their close relatives, which are called curtilage. Across the New World, so there's been a lot of action in snake evolution in the last, say, 2012 or 15 million years.

Nick Jikomes 12:32

So rattlesnakes are interesting. You also mentioned fruit flies, which was the animal that I worked with and that you worked on for most of your career. One of the things I learned early on in your lab and elsewhere was to say, you know, we didn't study fruit flies, we studied something deeper and bigger, and the animals were just a tool. So what are those bigger sets of questions that you were using them

Sean B. Carroll 12:56

for? Yeah, great question. I think just a really important question, when talking about science, like I think the art of this business is you try to find the simplest example of the phenomenon you want to understand. If you try to find the most complicated example, let's take something that I've never worked on, like the brain, but you have, and you start with, you know, an elephant brain or a human brain, you're dealing, you know, it's complicated, and it's hard to do experiments. So you'd move to something simpler. Well, in the case of the fruit fly, this tiny little animal, really in the building of that animal and its wings, and its eyes, and its legs and everything else. It's it's a, it's really just a microscopic example of anything that any other animal has to do. But they're very easy to keep they they reproduce rapidly. And because they've been sort of the workhorse for genetics for a century, there's just tons of tools that biologists have come up with, over the decades. So you know, I didn't say to my parents all I want to be a fruit fly biologist, or something like that. What happens is you find models of what you want to understand. And the fruit fly turned out to be a great model for animal development. So how are complex things built? On a great, go ahead?

Nick Jikomes 14:11

Why is that? How can How can a fruit fly teach us something about other animals? Well,

Sean B. Carroll 14:18

it's now an answer, I can get more in hindsight, because the honest the honest truth was in 1982, when I was deciding to go after my PhD and go study fruit flies, I had a few of my mentors say, you know, you're stepping off the edge of the earth because there is a bias in the biology community at the time that if you want to, you know that you had to study something relevant to humans. And that would mean studying animals with for like mice. And there was no expectation that something like a fruit fly, which is you know, an arthropod and invertebrate would be a model of anything for humans. But just but but there was so much fascinating stuff going on. Fruit flies. So the the phenomenon that launched 1000 postdocs was the discovery of these mutations called homeotic mutations. And they are mutations in single genes that transform one body part into the likeness of another. So antenna pedia, for example, transforms the antenna to leg, or mutation called by thorax transforms the hind wings to the four wings, so you get to fly with two sets of wings instead of one. And

Nick Jikomes 15:29

we will. So you mean, literally, a mutation in a gene will turn the antenna of a fly into another body park?

Sean B. Carroll 15:38

Yeah, into a leg to a nicely formed leg. And you think, man, I got to understand how that works. So when I first read about these mutations, 1981 1982, I was studying something completely different. I'm getting my PhD in immunology. And I thought, what could those mutations be? What are those genes be there in a single mutation could so transform the body of an animal, and they seem to have some sort of evolutionary significance because you sort of think if a gene can really sculpt a body part like that, well, what makes a lot of animals the different interesting differences between a lot of animals are the number and kinds of body parts they have. So I was hell bent that I was going to study jeans like this. And it was not really on the radar of many people at the time. And I approached a really young guy, in fact, somebody, Matt Scott, who was just opening his lap, he hadn't even opened his lab yet. I said, Hey, I want to work on on these jeans. And he said, okay, but, you know, first day in the lab was cleaning out the glassware of the lab, the previous lab that had left it all messy, and, and dirty, you know, we, we really started from from the ground together. But it was a good call, you know, again, wisdom was was, you know, the wisdom I was getting was, this was a really dangerous and risky maneuver. But I was driven by the biological interest, I just thought these mutations were so fascinating. The genes must be interesting. There wasn't, there weren't a lot of tools for getting a genes in those days, or figure out how they might work inside an animal. So even when I wrote for a postdoc fellowship, there was a lot of skepticism of whether or not this was even technically feasible to figure out how these genes worked. So you have to kind of sometimes you have to swim against the current and say, Look, this thing is so compelling, so interesting. I got to know I got to work on it. And fortunately, you know, I stuck to my guns, and then I got lucky. And I was in a great environment as a postdoc, it was really fertile. It was really, really creative things. A lot of things happen in a short period of time. And and to get back to your original question, why would a fruit fly be informative or interesting? right at that time, in fact, Matt Scott was a co discoverer of the fact that in these fruit fly genes, there was a little stretch of DNA that turned out to be exist in jeans, and earthworms and butterflies and mice and humans. And it turns out that those same body building and body patterning genes that sculpt the fruit fly, exist and sculpt us. And that was discovered in the 1980s. And it blew everyone's mind. I don't know of anyone who claimed that they saw that coming. But that was the sort of the revolutionary discovery that said, Oh, my gosh, not only are these fruit flies, interesting, I mean, they're a passport to the whole animal kingdom, which meant, if you wanted to study how to build a, you know, a mammal, they were a great thing to know about. But if you wanted to understand, how did the diversity of the animal kingdom evolve? Well, we were staring at the right genes to ask that question. And that was really my driving passion was the diversification of the animal kingdom. And so, you know, who knows what, what lessons there are in there except for, you know, we often make discoveries that nobody foresees. And they're sort of game changers in terms of people's perspectives. And also, individually, if you're really driven to ask a certain question, you know, I'd be the last person to tell anybody, you know, not to do it, because you got to do it. You got to do what makes

sense to you.

And, you know, I'm so glad that I, that I went after it.

Nick Jikomes 19:18

Yeah, it's interesting. There's almost a parallel I can see between the role that chance and adjacent opportunities play in the natural world and also in, in your professional world. So you, you were doing immunology, you weren't doing evolutionary biology, you were driven by curiosity. And things just sort of popped up by chance. And and you sort of seized on them just like, you know, when you describe the snakes, or the other discoveries that I know you've made, there's all these. There's all of these adjacent possibilities and evolution and you just sort of Tinker what's there and it opens up this whole new world, do you? Can you maybe talk about that in the current context of your first book, which is really about this whole field of how you build animal bodies?

Sean B. Carroll 20:06

Well, let me let me take that because the question is kind of a two parter, which is there sort of like the culture of science? And you know, how does the scientists get lucky, I guess, is part of it. And the second thing is, what's the parallel conceptually sort of actually how evolution works. So let me just go to the scientists side of it, the human side of that first, I was going to school graduate school in Boston, as you did. And I always looked around at the seminar postings of the other schools, and I would just hop on the T and go here seminars and interested me. Nobody told me not to do that. But I did that. And because of that, I just, I only went to things that I thought would be interesting, right? So I use that as kind of a r&d tool, right, if what else was going on in biology at the time, so I was lucky to be in Boston, which was such a fertile place for you know, almost every flavor of biology was going to come through Boston in a year, right. And anything new and different was going to come through Boston, because of the schools that were there. So there's, there's one chalk up, which is, you know, sort of being in the right place matters. And then as we just described it, I got interested in this stuff, and I pursued it. But I can tell you that about seven or eight years later, so I knew that I want to study evolution. But for a bunch of years, I focused entirely on the fruit fly, because what interested me was the evolution of body form, the number and kind of body parts, their patterning, etc. And it was important to get to that I understood and others understood that changes in pattern changes in form must be due to changes in development. Because form is made by development, this process by which an embryo grows up from a single cell and and into a complete creature. So it must be changes in that process that give you creatures that look different. So we have to understand that process in order to understand changes in that process. And I was thinking, Okay, I had to go hard on fruit flies to try to find out as many secrets of the fruit feel through the fruit fly as I could. But how is it going to study evolution. And one day, I was giving a seminar at Duke. And I was scheduled the way academic seminars work, I was scheduled to meet with a variety of people. And one person named Fred night out. almost didn't make his point with me because he had a pipe break in his house. But then we met. And Fred works on butterflies. And he said, Shawn, all this stuff you're discovering in fruit flies, do you think it could sort of explain this? And he shows, you know, sort of a case full of butterfly is spectacular butterfly wing patterns?

Unknown Speaker 22:37

I said, Well, I

Sean B. Carroll 22:38

don't know, Fred, but it's I sure as hell would like to find out. And that's how I got started working on butterflies.

Nick Jikomes 22:45


Sean B. Carroll 22:46

So that was a case of, I mean, you know, one of the few guys, I think in the United States I could have bumped up to but Fred was a huge expert on butterflies, sweet guy helped us get started. And that led to asking questions about, okay, where do new things come from? And so we started a program where as I was comparing, we were comparing different kinds of animals and asking, Well, if this animal over here has one set of wings, this NOLS two sets of wings, what's different between them? Or if this thing has more walking legs? This is fewer walking legs, what are the differences between them? And then new things? So one of the things that's prominent on some butterflies is they have these eyespots these beautiful concentric rings of pigmentation that look like eyes look like faults eyes on the wings. And Freda, study those any any was studying a species that had them and we brought those into the lab. And the hunch we played was, well, gee, we were studying the building of wings in a fruit fly. And we thought, okay, same genes are going to build wings in in butterflies, because wings have been around for 300 million years, they're going to use the same stuff. But what about the patterning of those wings? I wonder if they're doing anything new. So we just cloned out all these genes. And then we said, well, what are they doing in butterflies, and most of the genes were boring, they were doing exactly in butterflies, what they were doing in fruit flies, marking out various territories, etc.

But then one gene

absolutely beautifully foreshadow the formation of the eyespots. And that is one of those

that's one

of those rare Holy shit, Stop the presses moments in the lab, where you have no idea I had no anticipation of what that result would even look that we get a result like that, or even what it would look like until somebody called me over one morning and said, Shawn, this is what I see. And you know, I mean, it makes your heart race it makes your mind race, because you're like, Oh, my God, what I know, this is something I know this is something What could it be? And it turns out, we wrote this up in the first half of 1994. But it turned out it was probably the pioneering discovery that really kind of was the general would teach us essentially the generality of how new physical traits evolve. And this was an old, very old gene, a gene had been around for more than 500 million years, being used in a new way and those butterfly wings. And that, in a nutshell, was how body patterns were going to evolve. And as we studied more things over the next 15 or 20 years, that theme just kept in as labs across the world study things, that thing just kept coming back in the back that very old jeans was sort of learn new tricks and certain species and gave us new patterns. And that was really the root of, of morphological diversity. And, you know, never knew that we were going to get that first clue in such a visual, surprising, crystallin way, you know, one morning in the lab, but and when it happens, it's you know, it's it's as thrilling as I think, you know, anything that could happen to a, you know, a racecar driver or a musician, I think it's, it's got a I hope it's on

Nick Jikomes 25:58

par with that. Well, one thing, the thing that really blew me away when I was a teenager, when I was like 18, and I read your first book, endless forms, which is sort of about this whole field was I said, holy cow, sort of life makes sense. Now, there's not this inexplicable gap between humans, and bugs and other critters. It's all the same genetic ingredients, and you just sort of recombine them and mix and match them in different ways, essentially, and that can generate the actual difference, the astounding diversity that you said,

Sean B. Carroll 26:32

that's an interesting takeaway you got so yeah, the book. And as far as most beautiful with its, it, borrows some Darwin's last line of the origin of species. And I was talking about form I was talking about, well, how does all this incredible diversity of form of the animal kingdom evolve. And by that time, the book was published in 2005, we now knew we could say that basically, there was a common genetic toolkit, these body building and body patterning genes shared by so many animals. And really, what what made them different was the way they were used, not whether they existed or not, but the ways that they were used. And you're right, that closes a lot of the gaps between everything in, in the animal world to see that we are. We're just a little remodeled, you know, four legged animal, right? It's it once you see how to build a mouse building a human doesn't look that complicated, either. Building a fruit fly doesn't look that complicated, either. So you Yeah, that those genes gave us really a passport to the making of the entire kingdom. And really a logic, which was, you know, and were simultaneous discovery, people were starting to sequence the genomes of all sorts of species. And there was an expectation, for example, that humans have more genes than anything, right? Because we're so complex. And I remember being at meetings and taking bets because I was like, No way, man, you know, people are always gonna be 100,000 genes in us because there's like, you have 20,000 genes and a Mouser. And when 1000 genes and a fruit fly, this would be late 90s, late 90s, late nights, just so human genome comes out. Yeah. And the number may have been up in the high 20s. But that's come down and come down since then. It's like, yeah, it's you don't need any more genes to make a human than you do to make a fruit fly or a butterfly, you know, or a snake. It's you just use them in different ways. And, and really the the double sort of Whammy of that which interested a lot of people, surprised biologists, but then interested non biologists because they were like, you know, goodness, II mean, we're really, you know, genetically, you know, not only not that different, but not that much of a mystery. Just another, just another, you know, four legged animal in the animal kingdom. But that was those kinds of discoveries that people started asking me, you know, to be in documentary films, or for interviews with the press, or to give public lectures to explain the discoveries and what they meant. And after doing that for a while, that's what led me to write the book, I thought, well, goodness, I could either give this talk, you know, umpteen times, yeah. Or I could put all these thoughts in some organized way down on paper. And then, when the filmmakers came along, I thought, well, you know, film goes even farther, because a lot more people will watch a film, you know, an episode of Nova or something like that, then we'll read a book. And so, you know, let's do films. And that's what really catalyzed the whole science communication side was it Fortunately, I was in a field and directly involved in a lot of cool discoveries, and directly involved in communicating those discoveries. And it just grew from there.

Nick Jikomes 29:31

Interesting. So there was never a plan. It wasn't premeditated that Okay, I'm going to become a scientist in a lab. And now I'm going to start writing books. It just sort of spilled over from your curiosity, and people asked you to talk about it, and then you just sort of formalized what organically happened.

Sean B. Carroll 29:48

Yeah. And I think it was even somewhat connected to my teaching because I I always enjoyed classroom teaching I loved I liked the challenge of trying to communicate, you know, discoveries and ideas. thought to, you know, first timers right to students? And that, that hones a cert Well, you know, whether it's skills or not, you know, I did my best. That's all I can say. But that at least, that challenge is interesting. How do you communicate kind of what's up in your head? Or what the scientific community has found out? And how, how do you communicate that with people in a way that's accessible? I love that challenge, still love it to this day. And that's what always sort of that was the confluence of things that were sort of going on at that time that were, the research was incredibly exciting, new discoveries were happening at a pretty interesting pace in the lab, or in my colleagues labs around the world. And I was interested in this challenge of how do you communicate this? And no, it was no plan, the original plan, so 1982 83, I said, I want to study the making of the animal kingdom, I want to study, you know, how you get snakes and butterflies and giraffes. Okay, that was probably the real root motive. And I followed what I think was a fairly rigorous scientific path of what made sense, find out how some animal does it and then take that information to study other animals. But the public side of it, you know, there was no there was no anticipation that How could there be in a you know, if you're lucky in this business to make any discovery, let alone a discovery that somebody finds interest. And but as I said, I enjoyed the challenge. And I certainly must have enjoyed the feedback that I got, I think, a really important audience. Simultaneous with this, Nick was 2005, if memory serves was the year of the Dover trial, unintelligent design, I'm pretty sure I forgot about. So here is, to me a golden era, in evolutionary science, we've got access to the DNA record, the discoveries are just cascading out of labs, okay. And we've got this 19th century debate going on of whether or not evolution is, you know, is real. And so one of the most important audiences I met in this whole time period were biology teachers, in large numbers, like I got invited, invited to conventions. And I tell you, they're the most inspiring group of people to be around. This is essentially the, you know, this, this is the frontline army, for biologists and for the future of biology and science. These were the people who were taking this to, you know, large numbers of students year in and year out who spent, you know, day after day in classrooms with kids trying to get these ideas across. And I thought, wow, first of all, what have we discovered sort of new that can help them with that, either make it more engaging, or more sticky? And and how do we do that, and so that had catalytic effects. And some of the other decisions I made after that time, but I saw new ways to teach evolution because we really could go right down to the specific changes in DNA that changed traits. For decades. You know, evolution was sort of described in the abstract sense of, Oh, you know, genes must be changing for things to be changing. Now, we could show you which genes mattered which changes in which genes mattered most and exactly how they added up to making differences. And that was game set match in terms of evolutionary process. And, you know, for evolution deniers, it was game set match, right? It there's there was no, there was, there was no more sort of, you know, gap or uncertainty to try to point to,

Nick Jikomes 33:44

yeah, the, the subject of not just the denial of evolution by certain people, but the denial of different scientific findings has fascinated me. And it's a really important subject at a societal level. I think one thing that I found that I still find interesting about it is, it's not just one group of people in society that denies science. It's different groups of people denying different forms of science for different reasons. Can you speak a little bit about what you think the underlying psychology is around why people sometimes meet with science in a combative way?

Sean B. Carroll 34:21

Yeah. Well, let me start. So there's a piece if you don't mind me telling you so a recent piece I wrote on this, which would be a more organized and thoughtful digest and what I can, you know, verbalize today it's called denial. The denial is playbook, and it's online in Scientific American. And I sort of tried to unpack denialism. And let me go right to sort of the bottom line. What and I'm not talking about like doubt or silicon. You know, skepticism plays a big part in science let's let's define denialism. denialism is really disregarding consensus facts from the scientific community, okay, so, and at the root of that, which is denialism and the tactics of denialists are really sort of a rhetorical fog. They're throwing up all sorts of sort of objections and what ifs, and yeah, buts, and all this kind of stuff. These are just this is just a smokescreen for the fact that there is some fundamental, philosophical disagreement that they can't surmount. So in the case of a young earth creationist, well, evolution is irreconcilable with their worldview, you know, the world is, you know, the Earth is over four and a half billion years old, all of life evolve naturally, with no divine intervention. That's a different worldview than he unearthed creation, his hands. So they're only tactics they have left is just to say, what the scientists are wrong, they've misinterpreted all of their data. Or the scientists are malicious. And they are, you know, you know, militant atheist trying to undermine the American way of life, okay. You know, there are we're dangerous for even saying these sorts of things, or we would, you know, we're taking away their religious freedom. So there's this whole set of rhetorical arguments that are thrown up to try to sort of raise doubt in in some way or in other in their community's mind. So that's part of the psychology psychology is what happens when you confront facts, consensus facts, that are incompatible with a worldview. Yeah, another example for which comes from a totally different world, but it's in the article. And this is where this was, for me a formative experience in terms of learning about denialism was it has to do with the story of the polio vaccine in the mid 1950s. And chiropractors response to it. And it turns out that, that not everyone, but most chiropractors were opposed to polio vaccination. And

Unknown Speaker 37:01

I thought, Oh, wait, wait a second,

Sean B. Carroll 37:03

I grown up with this story is like one of the medicines greatest triumphs, you know, to to Fort this scourge that paralyzed people and killed kids. And in 1955, it was second only to the atomic bomb in terms of what Americans feared most. Oh, well, so polio, you know, as scary as Coronavirus, right, at least for sane people. And but the chiropractor's opposed it, and you're like, Well, how do they oppose it? It was a large scale clinical trial, it showed that it prevented the disease, while others well, simply put, well, chiropractic was invented in the early 20th century, and the theory of chiropractic was that all disease originated in the spine. And that manipulation of the spine was necessary to do this stuff. chiropractic was generously would say, at the time, you know, alternative medicine, it didn't use sort of the scientific method. It was never, you know, put to blind clinical trials or anything like this. So, and chiropractors had a pretty good business going of polio patients. So you have people that have, yes, they have spinal problems, they have mobility problems, they have partial paralysis. And so they're going in for spinal manipulations and things like this. So unfortunately, I think it just sort of boils down to both philosophical and probably a self interest. The self interest was it's part of polio, a part of chiropractic practice. And but philosophical was they were essentially opposing the germ theory of disease, the idea that microbes like viruses and bacteria, were the route of disease as opposed to misalignments of the

Nick Jikomes 38:45


Sean B. Carroll 38:47

And I thought, oh my god, okay, that's 1955. Okay, let's go 50 years later, a significant portion of the chiropractic community still opposes vaccinations, like routine child vaccinations. And when I wrote this article, only a month or two ago in Scientific American, I heard from chiropractic on both sides of the aisle. Someone said, Thank you, you caught you, you nailed my colleagues to the tea. Others who said, you know, what company are you shilling for and writing such an article, which, and for the record, I was paid zero, which is a typical rate you get in academia So, but, but this is what you hit and and whether it's climate change, or it's vaccination, or back a long time ago, tobacco smoke and cancer, when you have people who have some kind of interest in resisting the science or in the science not being true, you can see these rhetorical and then it becomes Of course, political, and then it gets, you know, all sorts of things happen. So the really important thing about denialism is to try to figure out how to sort of penetrate that fog. And fundamentally you got to ask me Why would these people be opposing? You know, polio vaccination? Why would well, you know why the tobacco companies would try to claim that tobacco smoke did?

I think

Nick Jikomes 40:10

so the thing about creationism, creationism makes sense because there's this deep, philosophical spiritual belief system that runs right against some facts. chiropractic, or the climate change, or the tobacco thing makes sense, because there's entrenched business interests that run against the science. What about something like, what about an upper middle class mother with a child who has autism who becomes a militant anti vaccination Crusader? Where does that come from?

Sean B. Carroll 40:38

Well, it comes from, from, you know, that experience because usually, you know, the child's autism might be diagnosed right around the time of childhood vaccinations, I've met such parents myself, it's hard for them to think that it was not caused by vaccination. And of course, it's, you know, a very for it varies for in terms of parents experience, but you know, severe autism is a tremendous challenge for parents to deal with. So it's coming from a very understandable experience. And there are going to be voices and sources out there, they're going to enforce that point, you're going to support that point of view. This all started in 1998, with Andrew Wakefield's now discredited study in The Lancet that allege that they saw a high incidence of autism and a small number of British kids close to their MMR vaccination and raise the question, Oh, my gosh, has autism being triggered by vaccination. But within, you know, three or four years very large scale studies in the United States, in Scandinavia and in Europe, could not replicate that much larger studies in the 12 kids that were in the Wakefield study. And so basically, the incidence of autism is the same in kids who are vaccinated kids who are not vaccinated. It's kind of fundamental. But nonetheless, 20 years later, it is very hard to get that thought out of people's minds. And to say, you know, there must be something to this, I heard it, there must be something to it, unfortunately. So I think it's, you know, I have a lot of sympathy for parents who confront this and are confused by all those voices that are out there. So because a lot of what denialism is is sort of just raising doubt, right? It's, it's, you know, can you really trust the pharma companies? Can you really trust the medical establishment? You know, did you really feel like you were treated? Well, when you For example, your maybe your kid was first diagnosed. So there's, there's a lot of momentum to the I don't trust this, this group of people. And I have another set of sources that I trust, and those might be vocal, you know, anti vaccination critics take RFK Jr, is, there's an editorial in the Washington Post in the New York Times today by his niece, because RFK Jr, is out there against the COVID vaccine. Again, he's been he's been an anti vaccination person for 20 years or more. And even though the data is, you know, doesn't support this whatsoever. There are still folks that once they took an entrenched position, it's very hard for people to walk back from those from those positions. So a mother that experiences this or, you know, our parents have a newborn, baby, first child, they're like, well, what should we help? My gosh, it's a big battery of vaccinations. I, you know, and who likes to see needles go into their baby. So they're hesitant for understandable reasons. But you know, that's where pediatricians and other kind of public health information comes into play. So I think it's understandable why there's vaccine hesitancy, I think it's, I think, you know, strident anti vaccination forces. You know, that it's, it's harder to unpack where they all might be coming from, it might be coming from a personal experience, it might be coming from a wider worldview, sort of distrust of Orthodox medicine or pharmaceutical companies. But nonetheless, you know, it was concerning. We made a film about six years ago, for Nova, called vaccines calling the shots and we kind of explored vaccine hesitancy for all these conventional vaccines. Okay, so maybe as vaccination rates were dropping, we have more cases of whooping cough, some some outbreaks of measles, etc.

that the human

toll of that vaccine hesitancy seems pretty modest. Now with COVID-19, if a third of the country decides not to get vaccinated, and if that is a point of view that's, you know, replicated around the world, perhaps even worse in some parts of the world, Oh, my gosh, we got a problem. We're not going to get rid of this thing. We're not going to get rid of this really nasty virus. And so the stakes now are sky high on for vaccination.

Nick Jikomes 44:57

So we're talking about vaccination. We've talked about And given the very special circumstance the entire world is in right now with COVID. Can you talk about viruses? So what what are viruses? How are they different from normal critters? And how can understanding the ways that they evolved and the ways they evolve differently from other creatures? What? What can that tell us about how we should be handling the situation today?

Sean B. Carroll 45:24

That's a great question. Nick and I were having this conversation, right, when there's, I think the reports this morning or last night, where's this? You know, new variant in Colorado? What does all this mean? Okay, so, viruses are circulating everywhere you and I've got a menace that viruses are little bits of genetic material that replicate inside host cells. So this is not, these are not things that can exist free living out on their own, like, say, for example, bacteria can or fungi can. So they require a host cell to replicate. And animals harbor a lot of viruses. And if you think of all the diversity of animals on this planet, there are a lot of viruses across the across the globe. And every now and then, when there's contact between humans and wildlife is, is an opportunity for viruses to jump from that wildlife into humans and event often referred to as spillover. So the virus is spilling over from a watt from a natural reservoir into humans. That's what happened with COVID. That's what happened with HIV. That's what happens, essentially, every year with flu and it makes a cycle through usually birds. Oh, really. So that about the flu. flu is recombining with viruses in in pigs and chickens and other domesticated livestock to get Okay, guess what, every

Nick Jikomes 46:46

year it's a flu every year most years it's it's it's a spillover event.

Sean B. Carroll 46:50

It's essentially it's a spillover event with luck. Yeah, yeah. So But getting back to something like COVID. HIV is another good example. But it's a of animal viruses coming into humans, and then setting and then being transferred from human to human to human. So viruses, there's, they are small, they're present in large numbers. When a virus replicates in your eye, it makes lots and lots and lots of copies of itself. So with lots and lots of copies of itself, there's lots of chance for evolution, because if you make, you know, a billion copies of a virus, those billion copies are going to carry a mutation here and there. And those mutant variants may have different properties than the parental virus. That's why For example, this variant is making news is because it looks like it might be a bit more transmissible than sort of the parent strain of Coronavirus. And if it's more transmissible, what's that going to mean in terms of how it moves through the human population doesn't look to be more pathogenic does not look like it makes any some more severe or less severe illness? It just may be, for example, bind new binding to ourselves a little more readily. And so a little bit of virus gets a foothold more easily than the the Coronavirus. So why is this all relevant to us? You know, we we live in a constantly evolving environment. And we nearly a billion of us are making a lot of contact with wildlife that we didn't necessarily make before through bushmeat or through encroaching and forests as we cut down the Amazon as we invade the Congo, etc, etc. That's where Ebola is coming from. So Ebola is coming from what we think is a bad host. And it's repeated cycles of infection spilling over to humans. So, you know, if you thought that evolution was just some subject that was for, you know, dusty books and fossils, and you know, old natural history museums, no, we live we live in a world where all sorts of things are evolving. The microbes that we try to treat with antibiotics are evolving. The viruses that are out there in the world are evolving. And as we've now experienced, these evolutionary events can have profound consequences for humanity. I can tell you that four years ago, we made a film on spillover and talked about Zika and Ebola and some other things like NEPA and flu. I never imagined something like this, I never imagined that a virus could spread so far, be so dangerous, and essentially paralyze human activity across the globe for a year or more now. I'm also glad that molecular biology has evolved very quickly and that we could develop countermeasures, like these vaccines, you know, faster than any time in history. So, yeah, so from a prospective point of view, you know, it's an accident, random mutations happen in viruses, just as they happen in us some of those random mutations change this property of the viruses, a chance encounter with the human and we're off to the races. So,

Nick Jikomes 50:01

you mentioned how fast we've been able to adapt to this virus, we've been able to basically go from zero to 100, in terms of vaccine development in a very short amount of time compared to historical vaccine development. What is different about how this new generation of vaccines from Madonna and biontech are working? And how does that impact our ability to try and stay? To keep pace with viral evolution? Yeah,

Sean B. Carroll 50:28

great question the way vaccines usually were made, say, let's say in the lowest tech era, were often just a killed form of the virus. So you grow the virus in vats of tissue culture in a lab, you didn't activate it chemically, or ultraviolet, or whatever it might be. And you inject that into people, so it's not able to infect them. But they're basically seeing the killed virus stimulates their immune system, enough that they have protection in case they see the actual live virus. Those vaccines, which we use for lots of things, so flu is an inactivated vaccine, you know, have generally worked, okay. But for some viruses, they're very, very difficult. aids, we still don't have a vaccine, because that virus mutates so quickly that basically it's there's, there's no virus, you could immunize people with it, we protect everybody against AIDS. So, and usually, because

the way we conduct

a clinical trials of these vaccines, there's a fair amount of sort of patient bureaucracy with this in that, you know, you take one step, and then it's sent off to the FDA, and it takes months to review. And then you start the next step. What happened was was all those things were compressed. So basically, the federal government stepped in and started funding, development of the vaccine, or the advanced stages of the vaccine before the other stages were sort of close so that these manufacturers could be scaling up the production of the vaccine before they even knew whether it worked. Otherwise, it'd be huge financial risk, if you start scaling up a vaccine before you know it works, and you find out it doesn't work. Well, you know, you may have lost a billion dollars and your shareholders are very unhappy. So basically, the federal government backstopped a lot of these vaccine developers so that they could be scaling faster so that they could jump into clinical trials faster. But there's also a technology shift. So instead of killed viruses, Pfizer and moderna, or biotech and modera, use a technology that's never been used for large scale vaccination. And that they are actually putting messenger RNA, which is a form of RNA that carries the genetic information for making one piece of the virus. They're putting that little lipid droplets injecting that into your arm and your cells make a little bit of the virus that then Prime's your immune system. So these are mRNA vaccines have never been used at scale. And goodness, nobody could have predicted they'd be as effective as the data turned out to be another thing about science, everybody's got to keep in mind, you don't know the results until you actually do the experiment. And for moderna and biotech, Pfizer, it just turned out really well. So there was a technological change. And the thing about Mr. mRNA vaccine was that as soon as those viruses were sequenced in China from patients, we could have the lab here, make those those molecules very quickly, and get them in tested in animals and start right on the course of vaccination. So everything was was sort of done in hyperdrive. Now, just today in the UK, a different vaccine made by Oxford, AstraZeneca was approved. And this is again, technologically something different, which is a little piece of the Coronavirus, the same part that's being used in the mRNA vaccine is in a vector, another virus a harmless virus called an anti virus to and this is a virus that can't replicate in ourselves but acts as sort of a shuttle to get that genetic material into ourselves making a little bit of the virus so that our immune system gets primed to it. So it's ready to go in case the real viable we encounter the real virus. So both of those technologies are ways of delivering the sort of important part of the virus that is involved in infecting ourselves. So this spike protein, it's on the outside of the Coronavirus. That's the sort of the key that unlocks the portal on ourselves. It gets a virus into those into ourselves. And if you block that key it can't get in. So that's the rationale for that for vaccine design. But researchers were working on Coronavirus vaccines for things like SARS and MERS. They had some years of experience with these technologies so that when this Coronavirus came along they said hey you know let's see if we can Make a vaccine this way. So it wasn't like the research did not exist. But really it was benchtop research for other coronaviruses that they then said, well, let's go for it. Let's see if we can make an mRNA vaccine. Let's see if we can make an ad a virus based vaccine. Another technology, which is just to make the spike protein as it is, that's the strategy being used by a company called Novavax. They're just entering phase three trials now, that's very similar in sort of design to something like the hepatitis B vaccine, which is pure viral protein. So that's a little later than these other vaccines. But this reflects, you know, the biologist tools for doing these things have changed a lot over the decades. And so we had more tools that worked a lot faster. So that lots of folks jumped in. I mean, this was a worldwide effort, and there's, you know, lots of vaccines under development. But, but, you know, because of the societal imperative, the financial backstopping of these companies so that they could start making 10s and 10s of millions of doses before they even knew the virus work. The vaccine worked. That was really important.

Nick Jikomes 56:11

So I've heard the new mRNA vaccines described as programmable. What does that mean? And what would it allow us to do if let's just say tomorrow, there's a brand new Coronavirus, strain, brand new mutation, the spike proteins now completely different. And the vaccines we have right now aren't as effective. How quickly could a new vaccine be developed?

Sean B. Carroll 56:34

Well, I mean, there, I'm gonna just it's just gonna be a speculation. I think it was 60 days at for the first one, that the session the vaccine was formulated. So I think it's probably 60 days or less that we'd be able to spike should use the word spike we so right now, the mRNA that's in there is for essentially the prototypical strain of Coronavirus. If we thought now that Coronavirus, had evolved enough that we wanted to have some variant or combination of variants represented in that vaccine, we could add the mRNA for those variant proteins to that mixture, same technology. So I think that adding a variant to the Pfizer vaccines, or the moderna vaccine, would be pretty darn straightforward. Now, I don't know the regulatory authorities might want a new clinical trial to make sure that that was protective. Or it may be big again, just because of the imperative because we're in the middle of a pandemic. And I realize most, most studies are done at a slower pace, because the urgency and the societal impact is not that great. That, you know, maybe the regulatory authorities would would allow use of that vaccine. Essentially piggybacking on everything was established about the first vaccine. They'd still want to probably gather data in the field, but they might allow the vaccine to go forward


all the steps to the trial now that essentially the principles been proven, you know, for the for the mRNA base base vaccines. So we would have a response and the end of virus is also programmable, so that we could quickly be expressing that variant. So I think it's, you know, I think it's 60 days that we probably be working on it, whether or not the regulatory authorities would allow that to go into people in large numbers without some formal testing. I can't speculate. But if this was something, you know, imagine this if two or three months from now, we found out there was a vaccine resistant strain, a strain that we didn't think was was was circuit starting to circulate that was not protected against by the vaccine. Man, I don't know, that's a really tough ethics call for regulators, which is, you know, the world is really suffering. And would you take that chance? I hope we don't have to find out, man. I hope we don't have to find out. But, you know, we feel good that we can respond on this timescale at the same time, every month going forward, you can see what the what the death toll and what the the, the the illness and the economic toll is going to be. So you know, my every month really matters right now.

Nick Jikomes 59:19

Yeah, it's it's amazing that the science is at a at a state where we can actually move this fast. It's it's absolutely amazing.

Sean B. Carroll 59:27

Yeah, it is amazing. And the others was one other part, which is probably unseen by the public. So they're getting the news reports that say, you know, the phase one data that came out, I can't I almost can't remember probably mid summer. That said, Look, when you put these vaccines into people, their immune responses are similar to people who got the real virus, you know, got infected and went to the hospital. Then the efficacy data surprised everybody. I mean, no scientist is gonna say yeah, I'm gonna make a 94 95% effective vaccine out of the chute. Lot of the vaccines. We have our 94 95% effective at preventing infection, that's just the way the biology works. So, you know, they hit it, they hit a Grand Slam first time at bat. That's, that's, you know, that's, that's pretty remarkable. So I think, you know, the scientific community has a lot to be proud of. But the invisible part is that, you know, the sharing of data and the sharing of studies because a lot of stuff is going to a lot of scientific studies of Coronavirus are going to these preprint servers, before they go to journals. This is an innovation that happened in science publishing over the last few years to sort of speed up the otherwise somewhat slow pace of formal scientific publishing. Now Coronavirus hits, and people are just sharing their findings. You know, before peer review, there's some risk of that. But the upside of that is, is that the information is getting in each other's hands much, much faster. And man, I've tried to, you know, penetrate the mass of that literature, when I go ask a question and say, Well, what do we know about patient's response, you know, three weeks in, and I find all these papers from all over the world. And it's just happening at lightning speed. So the ability for scientists to share information is unprecedented. And the amount of sharing that's going on globally, is unprecedented. Everyone's trying to learn as much about this virus and our responses to it and what works and what doesn't work as fast as possible, and sharing that openly. That's a pretty remarkable thing. Sure, we'd love to know more. We all you know, we we wish we knew in March, what we know now, and I'm sure we're going to know things this coming March that we wish we knew today. But But, but nonetheless, that that sort of all. Everything about the scientific enterprise is moving at a speed I've never seen in my lifetime, on the Coronavirus in particular.

Nick Jikomes 1:02:00

Yeah, it's amazing. So we've talked a lot about the role that chance plays in everything. What? So why don't you walk us through the new book and what it's about and and what inspired you to write this book now?

Sean B. Carroll 1:02:16

Yeah, well, I wrote it pretty much pre pandemic, but it was an editing when the pandemic came out. So I got to update that little bit. So it's called a series of fortunate events. It's about chance in the making of the planet life. And you. Why would I take up a book whose theme is about chance. And it's because I think it's an underappreciated force in the world. And the book, in particular, looks at this sort of geological, cosmological and biological accidents that make us us. And that sort of the astonishing series of things that had to happen for you and I to have this conversation for you and I do exist for us to collectively to exist for us individually to exist. And, and a bunch of stuff that's been discovered in the last 50 years that scientists go wow. And it's sort of some of the fun of the book and I try to make it fun. I guess that's almost a pledge to anyone who decides to read it shortest book I've ever written, trying to make it as digestible and as accessible. But you can almost think of as a bunch of what ifs. And the first one, if I start with is the asteroid impact. 66 million years ago, a lot of people heard about this asteroid hit the Earth 66 million years ago. And you probably know wiped out the dinosaurs also triggered a mass extinction and wiped out three quarters of all plant and animal life. Well, why is that a big one, if in terms of our point of view, while those dinosaurs and those large reptiles had dominated the earth for 150 million years, mammals were a real sort of minor player on the stage at the time, they'd been around a long time, but they were generally small, not too significant part of the ecology of the planet. But after you, after you cleared the world of the dinosaurs after that asteroid, mammals took off, and they got in a very short period of time, much larger than it ever been, and they became the largest animals in the oceans and on land. And some of those mammals evolved into primates and those primates eventually gave rise to us. So had that asteroid. Now let's add a little color to the asteroid to six mile wide rock that hits the Yucatan Peninsula 66 million years ago. Well, that rock may have been circulating the solar system, I don't know, maybe 4 billion years, and at one particular day, 66 million years ago and enters the atmosphere at 50,000 miles per hour and slams the Yucatan if it enters. Well, let me tell you a little more about the Yucatan we now appreciate that the Yucatan had the kind of mixture of rocks, sulfur and carbonate containing rocks, that when you vaporized all that stuff and shot up in the atmosphere, it made a really toxic stew as well as deflecting something Light. So basically, the world was in a blackout for probably 10 to 30 years, no sunlight or very little sunlight. So, plants collapsed. Everything that ate plants collapse, everything that dependent on things that ate those things that ate the plants collapse. That's why you had a mass extinction. But only about one to 13% of the Earth's surface has the right combination of rocks, that when vaporized could cause that mass extinction. So had that asteroid entered maybe a half hour sooner, it lands in the Atlantic, probably no mass extinction half hour later lands in the Pacific, probably no mass extinction. So that's a pretty big one. If, if that rock hasn't does not hit the Earth, or if that rock hits somewhere else on the earth, the earth might still be a reptile dominated world. mammals are a minor player, humans never come along. And I hope that's a little mind blowing for people to contemplate. It had we not been thrown this fastball from the cosmos. You know, we don't exist. Marvel Comics don't exist. Everything else that everybody depends upon, does not exist. And so the book has some of those stories, both sort of our collective existence, there's another big collision that involves the Indian subcontinent. Without it, we don't get the ice ages. Without that we probably don't get large brain humans. But even right down to you and I. So let's play a little let's play a little pop quiz. You're You're good at math. So you'll get this. But anyway, how many how many genetically unique children could any human couple have?

Nick Jikomes 1:06:37

Well, I cheated because I read the book. But if I try to go on my raw intuition, what do I think? I would think the answer was what I think the average person might think. I don't know, you might guess dozens maybe?

Sean B. Carroll 1:06:49

Yeah, yeah. 23 chromosomes was coming from dad. 23 chromosomes come from mom. So maybe it's 23 or 46, or 92. But it's actually more than 70 trillion. And so that means that no two of us will ever unless there's a identical twin, no two fertilized human eggs will ever be identical, ever. We are each unique. So we can, you know, cherish that right? It says but but that's because of just the random assortment of chromosomes. In fertilization, and the sort of the sperm race, were just, you know, one out of 100 million sperm that fertilizes the egg. And so each of us is essentially a biological accident, a happy accident, hopefully, but a biological accident. So the book is all about sort of the role of chance in our existence. And as I said, in the way that the planet is, and it, I hope sort of builds in people's minds is this understanding that we live in a chance driven world, you know, if you everything you look around and chance, deep within every organism, the process of mutation which gets it which gives us all biological diversity on the planet, is a chance process. That's how fundamental chances to the biosphere.

Nick Jikomes 1:08:08

One of my favorite stories in the book, is in the beginning, in the introduction, I think. And you describe a scientist that most people probably have not heard of, who is very famous among biologists. And this person said that the purpose of science is not to make new technology. So we just had a whole discussion about how amazing it is that science creates so much amazing technology, that this guy said that's actually not the primary the not the essence of science. So who was that person? And what was his answer to what science is really for?

Sean B. Carroll 1:08:44

Yeah, so this is French files is Jacques mano, Nobel laureate 1965. He was a pioneer of molecular biology. But as a Frenchman, steeped in his country's philosophical traditions, he was interested in what discoveries of biology had to offer some sort of to the to the philosophical discussion of of life, and felt it was really underappreciated, particularly at the time he was living. In the late 60s and early 70s. He felt that it felt strongly enough that he wrote a book called chance and necessity to try to bring these discoveries of biology to a wider audience. Now, it's pertinent, at least in my telling of the story, that he had been friends with albear kambu, writer, philosopher albear kemu, who is also interested in sort of, you know, is there a purpose in life? Why are we here, and when they met became friends, he now had, you know, one of the great biology living biologists of his time, as kind of a personal consultant that all matters all matters biological. But what minnow came to the conclusion of and this came directly from understanding molecular biology that this process of mutation is random and therefore the source of all diversity in the biosphere. All variation on complexity, all beauty is chance. And he saw the philosophical power of that which basically it vaporizes all notions of design and intent in the world, which is really, you know, 2000 plus years of Judeo Christian thinking. So but remember, these are facts from biology. So the philosophers were, you know, were riled up about minnow, because he was sort of infringing on their territory, but he was bringing new information and saying, Hey, we biologists say, look, you know, biology is, is driven by a, by a chance based process. You know, what does that mean? What should that mean to the world? So it prompted me to write this book, chance and necessity and, and it was a book I read as a teenager, and but I felt that that still chance was not as widely appreciated as deeply appreciated, as it should be. And it's, my nose book was 50 years ago, and he passed away only a few years after he wrote it, I thought, Okay, well, maybe it's time to revisit that with new discoveries. minnow didn't know about the asteroid impact. He didn't know about the plate tectonics, and it reshaped the world. He didn't know, necessarily the connection between mutation and traits, like we know, today, he didn't know about, for example, the origin of cancer. So I thought, let's, let's, let's update our thinking about chance with discoveries in the last 50 years. And I happen to have spent a lot of time in in sort of minnows trail. So I do this, I do this humbly, offering this this little update on our view of chance.

Nick Jikomes 1:11:42

So I love the book, by the way. So it's highly recommended by me that I think, you know, you've written a number of books now. So your best selling author, you're obviously a successful scientist. I want to get into the filmmaking stuff in a little bit. But I want to talk about actually, maybe the very beginning for you. So even before you got into science. And before you were letting your curiosity drive where you were going, once you were in the formal scientific world, what were you What were you interested in as a kid? What were you studying in college? Was it always science oriented? And and what was that like early on?

Sean B. Carroll 1:12:20

Okay, well, I think I know my origin story, you never know. You know, is it if it's accurate, but I'm pretty sure this is accurate. What I can start with. It's important, I give you a place, right, I grew up in Toledo, Ohio, on the city perched on the edge of Lake Erie, a lake that I never swim in or ate anything out of my whole childhood because it was notoriously polluted. It is not a hotspot about diversity. So as a little kid, and I grew up in a city block, which had nine houses on each side, you know, my whole neighborhood, I went on that block after block after block. So squirrels and pigeons were, you know, and an occasional Robin was the only wildlife in my backyard. But on the edges of the city if I got out into the woods, that's where I found frogs and salamanders and snakes. And that is what got my juices flowing. You'd flip over a log, you didn't know what was there. Oh, my gosh, look at that. Look at that. That's so cool. Look at that creature. Oh, my gosh. And they were just, to me fascinating. And coupled with at the time, there was a show on TV called Mutual of Omaha's wild kingdom, hosted by Marlon Perkins, who was the curator of the St. Louis zoo. And they went around the world to, you know, fascinating places. And you know, and looked at wildlife. And I just thought that was captivating. I know how much you know, Africa, the Amazon, the whole world was an amazing place. But I was in this rather rather domesticated place of Northwest Ohio. And so it was log flipping and I know this experiences of a lot of other biologists that we we discover in each other that, you know, if you like butterflies as a kid, are you like fossil hunting as a kid Are you like, or maybe you've lived on a farm and you like livestock and animals that's roots of a lot of biologists that I know. And for me, it was reptiles. And I just thought they were fascinating creatures. And I thought, okay, I'll, I'll study biology in college. Now, did I have any idea where that was gonna go?

Oh, hell no.

You know, what do you know? I mean, you got to think back to yourself, what did what did? What did you know at the beginning of where you might go? But what happened was I got taken into a lab early, sound familiar? And I got to see up close how science was done and then got invited to do some of that science and I love the lab work. I love the ability to design an experiment and then see what would happen. And so I became the An indoor biologist. So even though I had this great love of, you know, of wildlife in particular, you know, I became an indoor experimental, you know, kind of molecular biologist type. Because I loved answers at that level, I still do I love I love getting down to the absolute, you know, fundamental mechanism of something if if you can't, but as a kid, it was just, it was the thrill. And I think about this a lot, Nick, it was the thrill when you when you flip over a log, most of the time, there's nothing under there are just worms and millipedes, right. But when you find a Jefferson salamander, with this shiny black body with little blue dots on it, I mean, that's like finding the Hope Diamond, right? It's a huge visceral thrill, when you know, when you just out, you know, driving along the road, oh, my god, there's a snake in the road, you know, you hop out and check out this, you know, beautifully colored milk snake or something like that. That's what made my heart race. And I just, I didn't have a clear idea of what I could do with it. But I decided I wanted to study life and biology as an undergrad, and then I had enough people take me under their wing to sort of say, Okay, this is, this is how you become a biology student. This is how you then become sort of an apprentice biologist. And, you know, this is what we do. And I thought, Okay, this is, I'm gonna roll with this.

Nick Jikomes 1:16:29

I mean, a common thread here is that you've, you've always seemed to be curiosity driven first. And we've talked a lot about the role of chance versus planning, and your trajectory. So what what advice would you give to someone generally about how they should look at seizing chance opportunities that arise throughout life?

Sean B. Carroll 1:16:51

Heavy, I'd say, I've been in this position a few times, Nick, rec advice. And then I get an email later and says, Yeah, I'm giving up engineering for art. And I'm like, Oh, just don't tell your parents where you heard that. Look, full disclosure. My wife Jamie and I were parents of four kids, you know, that's, that's probably the closest, you know. You know, those are those are people closest to me in life. And and, you know, what advice do you give a child, and it's actually the advice I got from my parents. And and so as advice I gave my kids, which is my parents who said, you know, find something you love. I was the weirdo in my family. None of no scientists in my family, a lot of musicians. But, you know, I went out in the backyard and looked at stuff. And I thought, well, he's happy, let him do it. And my mom, let me keep snakes in my, my room. And let me keep nightcrawlers in the family refrigerator. And even though she was grossed out by them, she let me do that. So we said the same thing to our kids. And it turns out, they all went into the arts. So I have to believe that, and I truly believe for, you know, for happiness in life, you have to pursue those things that arouse your passions. You just, you just have to it doesn't mean you don't get to do it all the time, all day long. And you know, most all the artists I know, including my kids, there's some balance where there might be a day job that helps pay the bills by the while they, you know, work on a new song. But nonetheless, they have to be doing these creative endeavors, I think, to be happy to be fulfilled. And so you're asking, you know, what advice do I want to throw out there to people? I think if you can find something that you find fulfilling, you can figure out some way to make that make living at it. You know, you when, you know, I think if you can, I remember asking my youngest this, I said, you know how much your day this is post-college is how much he's musician? How much do your day do you get to spend immersed in music one way or another? And he said, Well, more than half I said, Man, I think you're beating the averages. You know, I mean, most jobs, you know, most endeavors, no matter what you find yourself doing, there's a certain amount of, you know, administrative work or, you know, time spent that you don't really relish, it just comes with the territory. But if you can spend a fair amount of your time doing things that keeps your juices flowing, keeps you passionate, keeps you motivated, whether that's working for a cause or pursuing the arts or pursuing science, you know, whatever, whatever it might be. I think that's what we're trying to find for ourselves, you know, hopefully in relatively the first half of life, you know, first 25 or 30 years. If you can find it, then I think you're fortunate and if you and if you can make a living at it, then Then you're doubly fortunate. It doesn't. They don't as you know, they don't go hand in hand.

Nick Jikomes 1:20:06

Well, you've, you've had a really interesting way of figuring out how to pursue your interest as a scientist, but then also tell those stories in book form, but also in the form of films. So talk a little bit about what you're doing for h h. MI, what is h h, EMI? And what is your role there? And how does it tie to filmmaking? And how to how did that happen?

Sean B. Carroll 1:20:30

kind of hold on for this talk. Alright, so I'm head of science education. h h. h. h. m is the largest life science philanthropy in the United States supports both basic research and science education. I run their science education programs I have for the last 10 years, I was motivated to do that a lot. Because I, I think it the teaching of science is really important. And then I thought there was some way I could contribute to both the content that's available to teachers, and to even the training that's available to teachers, and we're involved in both. But I'm also interested in the public communication, the science. And so one of the things I did when I got here with my trustees blessing was to start a documentary film unit that came from experience of being in lots a fair amount of films before that, and meeting a fair number of filmmakers. And feeling that one thing that a model that had not really been explored is to have scientists sort of right up there in the cockpit with filmmakers telling these stories. Generally, we were subjects that were visited by filmmakers, they did their shooting, they went back and, you know, edited these films, and then you know, we'd see them later when they were broadcast. And it seemed like a missed opportunity. In fact, myself, a lot of my colleagues, were not necessarily very happy with their product, nor were the filmmakers. I just kept asking my, you know, filmmakers, I came to know, you know, what was stopping you from doing your best work. And, you know, was there a different model that we could pursue. And so as a science organization, we started this documentary film studio, and brought in people from the industry. So my team is very seasoned filmmakers, seasoned industry, peoples, and journalists, folks. And what we basically do is tell stories about science and scientists on film. Now, some of those things we do for the classroom, I won't dwell on the NSA talked about that today. But the things that your audience can see are, you know, IMAX films for, you know, science museums, broadcast films that you'll see on, you know, PBS, or Netflix, or Smithsonian channel, things like that. And in different styles of films, more theatrical films that are a little more emotional and inspirational, as well as sort of more informational films about things like vaccination or spillover diseases, and things like that. But the thing about film is, it's the most immersive medium, we have it travels the globe very well. And a film can be seen by very, very large audiences. It also film can allow you to do things it's very hard to do in other media, it can help you imagine the invisible, or things that are sort of beyond the human scale of experience, whether it's the cosmos or, you know, life inside a cell. It can let you go back in time, you know, recreate things with actors and all that. So, you know, and it's, it's a popular form of entertainment. So science has a lot of stories to tell, and we just have to be good enough at telling them that people want to hear these stories as much as they want to, you know, hear stories from other fields of, of human endeavor. So, I don't know if that gives you that's that in a nutshell, because anything longer, that would be a long time, because that's a lot of evolutionary steps to go from, you know, right, starting to write books to working with actually some of the best filmmakers, documentary filmmakers in the world that tell some of these these science stories. So look, I the thing I just want to underscore is that the craft side of that, these storytellers, their ability to tell a story visually. I'm astounded at times moved. I remember, there's a one of my books, Serengeti rules was adapted to film. And filmmakers decided that they wanted to sort of tell the origin stories of a few of the ecologists that are in the film. And I was visiting in London, the producer was in London and I we went to a screening room around the corner in a London theater, just to see some early work, some early cuts. And I watched and I said, Oh my god, every one of these scientists is going to have a tear going down there their eye because they captured. What you and I've been talking a lot in this past hour. They captured that passion. They captured that curiosity. They captured. Why would somebody go out in the world for 50 years into a remote part of the planet and And just devote their lives to asking a question and understanding how nature worked. And they, they caught it and and they conveyed it and that's you know that's a talent that is scarce in general but when when paired up with I think with some scientific aptitude it hopefully it's a it's a potent mix film won an Emmy by the way for best nature documentary. So I'll just, you know, give give, give credit where credit's due

Nick Jikomes 1:25:28

and what was the name of that one again, the Serengeti rules, Serengeti rules,

Sean B. Carroll 1:25:32

screening screening on PBS right now on PBS is nature, it's screening for free. So if you want to check it out, go ahead. But it's a that's to me is a good example of combining the art, the visual art and storytelling with the substantive and important scientific story, another one I threw out there, which is also screening, streaming for free. It's called the farthest It's the story of the Voyager missions to the to the outer solar system launched in 1977, also won an Emmy for best doc. And it's a hell of a story. And and again, great, great filmmaking with a great story. It's, it's, you know, these are, these are, these are these are, they're, they're kind of the equivalent of the eureka moments in the lab, sometimes things come together. And what happens is better than you could have imagined.

Nick Jikomes 1:26:22

One, one of the last things I want to ask you about is, you know, we've talked a lot about chance and opportunity and creativity, and spontaneity in many ways, but at this point, you've written several books, let's just talk about the book writing process. Yeah, you must have some kind of creative process. So your last book, you know, you're gonna write it, you're in the middle of it, you know, you've got to get x chapters out, paint us a picture of what what does it look like when you've got your sleeves rolled up? And you're doing the work? Yeah,

Sean B. Carroll 1:26:53

so when I when I have no I've gone for. So that was a book that probably incubated in some embryonic form for five or six years. Before I tackle it, I thought there was something there that I wanted to do. But I couldn't, couldn't quite see enough of it to do it. But once I saw enough of it and kind of knew stylistically some things I wanted to do. There's a little light heartedness in the book you may have noticed, you know me well enough to know that I would be thrown off one liners from time to time, but I haven't necessarily done that a lot in books. So once I got in, sort of, I think the right headspace for telling the story the way I wanted to,

Unknown Speaker 1:27:29

I'm on

Sean B. Carroll 1:27:30

my back patio on a summer morning at 630. In the morning, I wake up while everything's fresh, get to a quiet place. And if I can write for two or three hours with no clock with no timer ticking, so like, the worst thing for me is like, I gotta be somewhere 830 Oh, I have two hours. It's what if it's not flowing? Then you're like, Oh, no, I got one hour, ah, not a morning shot. So I need you need enough buffer time there that if it's flowing, you can just go all the way you can stick with it and get get it all out until you're just like, Okay, I'm out. Now I can go off and go to the day job. But it's that kind of process day after day. And I need to keep my momentum up. And that was I can't take many days off from writing. It feels like the rock slides back downhill on that, that right there. And then you hit you hit like a knot or something. You're like, ah, where am I going to go with this this way? Am I gonna go that way. And you also have to be patient enough that you'll go somewhere, you know, with a story, and it's not working and you have to tear it up and back up and go another way and that's the Oh, that's two days lost. He just, that's just part of the game. But I think that momentum is really important that headspace that you're in, for me is really important and, and maintaining that it's almost it's not a trance, it's like a very soft trance, you start to become unaware of the passage of time. You're deep in the story, you're kind of in your storytelling, voice even. And you can feel that you're not getting interrupted, you're not answering the phone, you're not looking at email or anything else like that. You're just in your storytelling voice and you're just trying to tell the story tell the story as engagingly and as clearly as you can. And, and, and to do a book length project Boy, you got to keep that up, you know, for months and months and months. You know, that gives you that gives you a little glimpse, ya know, another book for another book that was three years and that that that couldn't be I couldn't do it day after day for three years. This book was manageable in probably about a year's time.

Nick Jikomes 1:29:46

Okay? You mentioned your lightheartedness. And that's something I've always appreciated about you. I there was something I read in the last book that I didn't expect except once I read it, it made perfect sense. You mentioned this stand up comedians, and you talk about this weird or maybe not weird similarity that stand up comedians and scientists have. So what what is that?

Sean B. Carroll 1:30:11

Okay, so I was realized, so I love stand up comedy for whatever reason I love a good laugh. And, uh, especially with, I have two boys living in LA, and you go to LA and all the comedy clubs have just top line acts and I live in DC now and I can pre COVID could go to lots of comedy. So I go to a lot of stand up comedy and developed as fans of all sorts of people and I realized Louis black, Sarah Silverman, Bill Maher rekeyed, your vase, Bill Burr on you go. They deal with, for example, religion, or sort of the accidental nature of life in their acts. And I thought, first of all, maybe it's why I like them. But second of all, it's kind of brave, because it's not an area that people are comfortable with. They're pretty explicit about saying, you know, hey, this is all there is. There's nobody in charge. And and and I thought, well, why is this why did Eric idols and other and I so I reached out to some folks including Eric Idle of money, Python, who answered a bunch of questions that I get to communicate with my one of my all time comedy idols. And I just wanted to get it this of why is it in their act? And why if I think of all people in all sorts of walks of life, it seemed like comedians, there are a disproportionate number of comedians that saw the world is chance driven, as as you know, as accident predominating Seth MacFarlane is another and there's a story in the book about Seth, who was, by a hair's breadth, missed the plane on 911. And Eric came back to me and said, it's, it's about truth telling Eric Idle and I thought, Holy smoke, how can I get to the age I am and not understand sort of, and then I read I'm reading these interviews with Joe vase and Bill Maher and, and truth telling, just keeps coming up, left, right and center now that now that I'm alert to it, I'm like, Yes. They see themselves as truth tellers. And of course, well, that's what we scientists see ourselves as we're, we're trying to find out the world as it is not some construct of a way we wish it was. But how does it work? What is it is what does that mean? Okay, we're here by accident. Okay. There's nobody looking out for us. There's no preset, you know, purpose or whatever it

might be.

And I'm finding all these comedians who think that way and and who reflect that in their work. And so that that discovery of comedians and scientists having

truth telling, as as their their common Modus I, I just thought it was fun to explore that at first,

I was funded to me to sort of, quote, discover it, or discover it for myself anyway. And then to explore that. So the last chapter in the book is this conversation about chance, which is it's a synthesis of thoughts from dead people like Kurt Vonnegut, and Albert commu and chochmah. Know, comedians, who took the time who had time to answer me like Eric Idle other interviews from folks, like, record your vase. And because when you get into this area, talking about chance, inevitably, people ask, Well, you know, if it's all chance, what purpose is their life? What meaning is there in life? And I knew, I thought that readers would want me to go down that road. So I didn't last chapter, but I did it. With this, these assembled guests that I wanted to have a conversation with, which was kambu, who takes the deep philosophical approach. Vonnegut who takes kind of the serious satirical literary approach, you know, durveys, and an idol who take other approaches and, and, and hopefully that conversation was interesting. I had fun stitching it together.

Nick Jikomes 1:33:59

Yeah, no, it was a lot of fun to read for sure. So, last few minutes here, why don't we just close out one more time? What's the latest book? What's the latest film that's out there? And where can people go to learn more about you and what you're doing?

Sean B. Carroll 1:34:15

Oh, goodness. Okay. So latest book is a series of fortunate events, chance in the making the planet life and you and I've given you that information, including there's a two minute animated trailer for the book, which I think is a good way for people to sample and see if it if it if it tickles their sensibilities, then hopefully the book is worth it. Films we mentioned, I think the Serengeti rules and the farthest would be to sort of exemplary films as they've come from our studio. Right now. There's also a film on demand. If you look it up, it's called Oliver Sacks his own life. It's a documentary about the life of Oliver Sacks, very powerful, directed by Rick burns. So that's one of our current releases that's out there got the release. The theatrical release was affected by

COVID but it's being released in a mechanism that helps support theaters at the same time making it available on demand and more stuff. Gosh, if you if you really want to find anything more about me there is a My website is Sean B Carroll calm. And there'll be a little bits there about past books and ongoing film activities and, and things like that.

Nick Jikomes 1:35:22

Well thought, Shawn, thank you for taking the time. I really appreciate it. You've been for like 15 years now you've been my scientific role model. You've also been my facial hair role model. And I think your you know, your books are a lot of fun to read. They're super interesting, and I think people are going to really enjoy looking you up. Well, thanks, Nick. I'm glad I at least had the judgment when this kid came into my office

Sean B. Carroll 1:35:48

and stunned me by telling me he had read endless forms most beautiful wanted a slot and lab that four years later, you proved you know, an immensely talented, hard working incredibly thoughtful. Scientist did a great piece of work as an undergrad, which is very rare as it is great and influential piece of work as an undergrad. So, you know, let's keep having these conversations. Thanks, john.

Unknown Speaker 1:36:13

Thanks, Nick.


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