Bringing Extinct Species Back to Life | Dr. Beth Shapiro

Huberman Lab

Dr. Beth Shapiro joins Andrew Huberman to explore the science and ethics of de-extinction, explaining how synthetic biology tools developed for resurrecting species like woolly mammoths and dire wolves are simultaneously advancing conservation

Key takeaways

• Dr. Beth Shapiro serves as Chief Science Officer at Colossal Biosciences, leading de-extinction projects for woolly mammoths, dodo birds, and dire wolves using multiplex genome engineering.
• Modern humans carry 2% to 5% Neanderthal DNA, with specific variants influencing immune responses, pain sensitivity, and disease susceptibility like severe COVID-19 outcomes.

Main topics

• De-extinction technology and synthetic biology
• Ancient DNA and human evolutionary history

Notable quotes

"Species is a human concept. We have this incredible proclivity to want to put things into boxes so that we can talk about them."

Conclusion

The episode underscores that de-extinction and synthetic biology are not sci-fi fantasies but active, regulated

Transcript preview

Speaker 2 (0:00) So our dire wolves, they have 20 edits that we picked and we sequenced genomes from fossil dire wolves. We learned from those genomes what genetic changes made those animals bigger, more robust, light colored in coat. And then we engineered those changes into a gray wolf genome to recreate the dire wolf. You know, I often get the question of why are you thinking about bringing extinct species back to life? Why aren't you thinking about helping living species not become extinct? And the answer is we are doing both. It is the same tools. It's the same technology. It's the same needs. And when we excite people with the idea of mammoths and dodos and thylacines, we get more engagement and enthusiasm and investment in developing the technology that we can use to stop living species from becoming extinct. Speaker 1 (0:52) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. Speaker 1 (1:01) I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Beth Shapiro. Dr. Beth Shapiro is an evolutionary biologist. She was a professor at UC Santa Cruz and an investigator with the Howard Hughes Medical Institute before leaving to become chief scientific officer at Colossal Biosciences. Her work at Colossal is focused on what is called de-extincting species such as the woolly mammoth, the dodo bird, and the dire wolf, meaning bringing them back to life. But that entire initiative is also about species preservation more broadly and how genomics can be used to improve the global ecosystem. In this episode, we discuss what it means to use ancient DNA to bring back extinct species, which then led us to a broader discussion about genetic engineering in human health, both of which, by the way, are happening right now. So this is not just a projection into what's coming in the future. As you'll see, Dr. Beth Shapiro is truly a one-of-a-kind thinker. And today you'll learn the science, the ethical implications, and the positive potential of using genetics to de-extinct species and using genetic selection and genetic tools to change humans. And no, Dr. Beth Shapiro is not planning to bring back dinosaurs. And today you'll learn why. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Beth Shapiro. Dr. Beth Shapiro, welcome. Thank you. Long-time fan of your work. Same. Love animals, love stories about animals that aren't around anymore. Heard that you're going to bring back the woolly mammoths, the dodo bird, and that you might have already done something to contribute to the proliferation of the black-footed ferret. I'm a big fan of mustelids, of which ferrets are. We're going to talk about all of that today, including the ethical implications and so on. But I have a very basic question, which is, how do you decide what a species is? Because you have a degree in zoology. I always wanted to get a degree in zoology. But a few years ago, we got this thing called DNA sequencing. We can look at ancient DNA, can look at skeletons. People have done that for a long time. And my understanding is that it's completely revised the understanding of the relationship between different animals and the number of branches in these phylogenetic trees. So what have we learned that I think people might appreciate understanding about taxonomy and like, is my dog as a bulldog mutt? really the same as a chihuahua? Are they really the same species? Right. Speaker 2 (3:42) That's a really fascinating way to put it. And I think the most important thing that most people probably don't think about is that biology doesn't care what species you are. Species is a human concept. We have this incredible proclivity to want to put things into boxes so that we can talk about them. So that we can have conversations or share stories or share memories. In order to share something, we have to know what to call it. That's one of the reasons language has been so fundamental to the evolution of our species and our social structures. So what is a species? Probably when you learned about species in biology class when you were in middle school. You learned about Ernst Mayr's biological species concept. Speaker 1 (4:27) Kingdom, phylum, order, genus, species, like this kind of thing. Clade, you know? That's Speaker 2 (4:31) the taxonomy, right? So we have Linnaeus came up with this idea of doing taxonomy, right? So here's an interesting taxonomy story. I've spent a lot of my career working on bison. for unfortunate reasons, probably, or fun reasons or whatever, but a lot of time working on bison. And bison were called buffalo, right? We think of American bison as buffalo. It's the same thing. It's the same thing. But bison is the taxonomic name that was given to American buffalo by Carl Linnaeus. Because when Europeans were going around the world and finding for the first time, Europeans had seen all these different animals, if they saw a big animal that looked like it would make a good coat, That was called a bouffe coat. They called it a buffalo or a buffalo, right? So we have African buffalo and Asian buffalo and American buffalo, and they are not related to each other at all if you look at their DNA. But they all have the same name because they all made a good coat at some point, or at least there was the idea that they would. But taxonomists found this to be very disturbing. We want to know what animal. we're talking about when we say the buffalo. And so this is why Carl Linnaeus comes up with this scheme. The American bison, the American buffalo is called bison, bison. In fact, the plains bison is called bison, bison, bison. That's a genus and a species and a subspecies that are all the same thing. Speaker 1 (5:53) That's the Latin name, bison, bison, bison. Bison, bison, bison. It's almost as humorous as I think it's gorilla, gorilla. Yes, gorilla, gorilla. Speaker 2 (6:00) And llama, llama. That's one of my favorites too. Speaker 1 (6:02) Love it. Speaker 2 (6:03) Anyway, taxonomy. So we have these taxonomic ways of thinking about things, and that sorts everything into your deep evolutionary history. But species concepts are what people use to try to say, okay, I have this animal. Is it in the same species as this other animal or a different species from this animal? And the species concept that you probably learned, Ernst Mayers, is the biological species concept, which says if they can breed and their offspring are fertile, then they're the same species. Which Speaker 1 (6:30) seems like a... Good place to start. It's a good place to start. Because even in my understanding from my fly biologists friends is that you can't mate Drosophila with another species of fly and get a fertile offspring. So even among flies, there's some restriction. And what's wild is that flies and mammals of all sorts seem to know. Like they actually don't try to mate. In most cases, they don't try to mate with... other species, which is fascinating in its own right. We Speaker 2 (6:58) might beg to disagree there. I mean, if you've seen your dog, your dog probably tries to mate anything it comes across. He just hit seven Speaker 1 (7:04) months. I've not seen him hump a single time. He's still intact. This time I'm keeping my dog intact. We can talk about the reasons for that. It's health reasons. I might get him a vasectomy. We never talk about this, right? You can keep your dog intact and just give him a vasectomy if you don't want him to breed. Yeah, right. A guest on this podcast said that, an animal expert from the Karolinska. That makes so much sense. She said, you know, in Scandinavia, it's actually, she claims, and I believe her, that it's illegal to neuter a male dog unless there's a health reason. In Scandinavia and Australia, the inverse is true. Of course, they're upside down, but we'll forgive them for that. But yeah, they need their hormones for proper brain development. And we worry about them running around and breeding. There is this thing called a vasectomy, which is actually less invasive a procedure. than the full neuter. Anyway, we don't want to digress too much. My dog doesn't try and mate. I didn't Speaker 2 (7:52) see Speaker 1 (7:52) my previous dog try and mate with cats or even chihuahuas. Do you Speaker 2 (7:57) think Neanderthals and humans are a different species? Speaker 1 (8:00) I don't know, but I want to know if we are all. the same species. This is an edgy topic, right? But if humans, I mean, if it's somewhat based on nomenclature, and if there's enough genetic variation out there, is it the case that people that we call people are actually divergent enough in terms of their DNA that two people are not necessarily both homo sapiens, that there's some homo sapiens with an asterisk? I'm not trying to cast any hierarchy. They could just be different. Speaker 2 (8:30) So you're referring to a different species concept, which is the genetic species concept, where an organism is classified based on some threshold of sequence similarity. And that is a species concept that is as valid and valuable a species concept as the biological species concept, which says you can't interbreed. If you're interested in conserving species, you might use a geographic species concept that says if you live here. You're a Florida panther, but if you live in Texas, you're a Texas panther. We're going to call you different species. Biology doesn't care about your species concept. Your species concept is something that you have adopted to have a conversation with another person about a particular topic. Speaker 1 (9:12) Educate us on this Neanderthal piece. I know this is a topic very close to home, given that your husband works on these issues. And maybe we'll get him on here separately, but feel free to steal his thunder in any way that you feel. Speaker 2 (9:25) My husband, Ed Green, was part of Svantipavo's group when they were assembling the Neanderthal genome. And so he spent a lot of time thinking about Neanderthal. I think what's interesting from a species concept, if we start there with what's going on with Neanderthals, is we now know. based on studying DNA, both from Neanderthals that used to be alive and a different lineage of human called Denisovan, we call it this, that was first isolated again by Svante Paabo's research group from a tiny little finger bone that they found in a cave, Denisovan cave in Russia. That's why they're called Denisovans. We know that there were multiple different species or lineages or whatever you want to call them of human-like people that were alive at the same time. And we know that after people moved out of Africa to colonize Europe, they met our ancestors, Homo sapiens, anatomically modern humans, everything you want to call them. They met groups of Neanderthals and they bred with them. So if they were a different species, they were violating the biological species concept at this point. So again, species concepts are just what we make of them. And today, most people... have somewhere between 2 % and 5 % of their DNA that is from this admixture event, this hybridization event between anatomically modern humans dispersing out of Africa and the Neanderthals that were already in Europe. Speaker 1 (10:47) Many questions about this. First of all, and try not to laugh, the silhouette diagram that we've seen of apes gradually in sort of time sequence working their way to bipedal and upright. When we see that diagram, Is that substantiated by the fossil record? It Speaker 2 (11:04) is, yes. We know that the lineage that eventually became us evolved in Africa. We can trace ancestry back to apes and then to primates, or primates and then to apes, and then eventually to us. The fossil record in Africa is very fragmentary. One thing that's been really fun about working in ancient DNA is the field of paleoanthropology. Pretty contentious because there are so few bones that are out there that if someone finds a bone and it's a partial fragment of a jaw with a piece of a tooth in it, they can use that bone to completely revise what we think has happened in human evolutionary history. And maybe they're right and maybe they're not. And they're smart and they've been thinking about these things and they compare it to all the other bones. So there's a lot there. What's brilliant about ancient DNA is that if I can find a little pinky bone in a cave and Denisova, right? and I can get DNA from that, I know that my bone has ancestors, right? If I have a bone that might be somewhere on that lineage to human evolution, I don't know that that bone has descendants. I don't know that that bone is part of our actual family tree, or if it's another one of the dead ends that went in a different direction and eventually became extinct. But that is one of the coolest things about being able to sequence one of these bones, because now you know what it is. And now you can line it up against all the DNA from all of the people that are alive today and discover things like we all have ancestry because there was breeding between these lineages, because they could, and because I think that if they can, they do. Speaker 1 (12:38) I would like to take a quick break and acknowledge one of our sponsors, Juve. Juve makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast is the incredible impact that light can have on our biology and our health. Now, in addition to sunlight, which I've talked about a lot on this podcast, red light, near infrared and infrared light have been specifically shown to have positive effects on improving numerous aspects of cellular and organ health. 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Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. Eight Sleep just launched the Pod 6, which is their most advanced sleep system. The Pod 6 is half the size of their previous models, it's 20 % faster with its cooling and heating, and it has nine times as many sensors for tracking your sleep. The reason why Eight Sleep is so effective at improving your sleep quality and duration is because it helps control your core body temperature. And the reason for that is that in order to fall and stay deeply asleep, your core body temperature has to drop by about one to three degrees. And to wake up feeling completely refreshed and energized, you actually want your body temperature to be increasing in the final hours of your sleep. Eight Sleep automatically regulates the temperature of your bed throughout the night and is monitoring your sleep and dynamically adjusting the temperature of your sleep environment so you get the maximum amount of deep sleep and rapid eye movement sleep. I've been sleeping on an Eight Sleep mattress cover for nearly five years now, and with each new iteration of Eight Sleep, it gets better and better at figuring out what my body needs in order to get the best possible night's sleep. And of course, it provides me excellent data about just how much deep and rapid eye movement sleep I got. If you would like to try it, Speaker 1 (15:26) It's interesting, right? Because if you took the far ends of the spectrum of the, you know, the old world primate, you know, apes, and then the upright human walking, my assumption is that let's just say you used artificial insemination that you wouldn't actually get. viable, reproductively competent offspring from those. But at some point, two different species, again, it's Speaker 2 (15:47) a Speaker 1 (15:47) nomenclature at some point, but two non-genetically similar, I don't want to say identical because they're not twins, right? So I don't have a language here, forgive me. But you can get breeding across species and get reproductively viable offspring. That has to be the way this happened, right? It couldn't have just been through spontaneous mutations that suddenly... took animals from quadrupeds to bipeds? No, Speaker 2 (16:11) this is a very long and slow evolutionary process. It's actually a really good question. And I think it's an open question in evolutionary biology. And it's probably different. Evolution does happen because of random mutations that accumulate in a genome. And if you think about what might happen if two lineages are isolated from each other for a really long time and in different habitats, say, this lineage is adapting to the habitat that it's in, maybe. it's very rainy and there's a lot of water and there's a lot of floral plants. And over here, it's drier and there's really scrubby plants. There's different selective environments. And as mutations arise in that genome, different ones will go to fixation. The size of the population also matters. If a population is really small, even mutations that arise that are bad can become fixed in that population just because. The population is small and it just happens by chance. And so over time, these two will become more and more different from each other. So what happens when they come back in contact with each other? I think it will really depend on what those mutations that arose over that time was. It could be that there's a very... short evolutionary time, but a mutation has arisen, that means the sperm can't fertilize the egg or the egg can't subdivide properly if you have a hybrid ancestry. Or it could be that nothing really has happened over a really long evolutionary time and admixture can happen. Speaker 1 (17:37) Humans Speaker 2 (17:38) and Neanderthals diverged somewhere 300 to 500,000 years ago. That's not very long ago in evolutionary time. Brown bears and polar bears diverged about half a million years ago, and we know that they can readily interbreed and do whenever they overlap in habitat. Yeah. They're called growler bears or... Pizzly bears, depending on which direction. Pizzly bears. I know, they're terrible names, right? You want a different name for this really cool bear. Speaker 1 (18:03) Yeah, Speaker 2 (18:03) especially Speaker 1 (18:03) if Speaker 2 (18:03) you're a Speaker 1 (18:03) bear. Yeah. But Speaker 2 (18:05) that's been happening throughout their evolutionary history. We can see this because using ancient DNA, we were able to go back. We found a polar bear off the coast of Alaska that probably lived more than 100,000 years ago. And it had ancestry that we see in brown bears everywhere in the world, suggesting that that... bear's ancestors at some point, or that bear's descendants had hybridized with brown bears and that DNA got passed around. We know that during the last ice age, there were polar bears that got trapped on the ABC Islands in Southeast Alaska. And when brown bears expanded from the mainland, they interbred with those polar bears. And brown bears all alive in North America today have polar bear ancestry that is because of that interbreeding 20,000 years ago or so. Wow. Yeah. So in that case, a half a million years had gone by. They're really adapted to different habitats, and yet they can interbreed. But what's most interesting, and I think is relevant to your question, is that those hybrid bears only ever live and survive as brown bears. We see no evidence of brown bear DNA getting into polar bears. And that is, again, because of... how evolution has worked. And it's especially interesting because it only really happens in the direction where the mom is a polar bear and the dad is a brown bear. Polar bears are induced ovulators. So the presence of a male will cause them to ovulate. So you can imagine a situation where a brown bear wakes up from hibernation, goes on to polar bear habitat to scavenge for food, comes across a polar bear female, induces ovulation, and they mate. The other way around, where a polar bear male finds a seasonally ovulating brown bear female, Mel probably wouldn't happen because the timing of overlap wouldn't be right. And also he would probably kill her rather than mate her because of the size difference and difference in what they're doing. So why is it then that since... bears live with their moms. All the brown bears that we see that have polar bear ancestry are brown bears, not polar bears. We were working with some polar bear biologists. We were doing this analysis many years ago, and their hypothesis was simply that if you have brown bear ancestry, you don't have perfectly white fur and you cannot successfully hunt seals. So it is just. adaptation, that means that that admixture doesn't work, right? So even though there's no problem with the sperm and egg mixing and the animal is born, they cannot survive as polar bears. And so polar bear stays separate from brown bear in that way. Speaker 1 (20:30) I'm going to bring up dogs again, but in the back of my mind is a conversation about humans and this question about different species of prior to Homo sapiens or Homo sapiens and nearby species having reproductively competent offspring. So In the dog world, it's well known that the English bulldog, which has a big head, small hips, is the byproduct of many crossings. But it's basically the bullmastiff and the pug. And this was an attempt to generate an animal with a short snout so it could clamp down for bull baiting, which fortunately is an illegal sport now, to clamp down and not get shaken off by the bull very easily. The floppy face is associated with lack of pain receptors. So a bunch of things in the bull mastiff lineage that they want, but they wanted a low center of gravity. So they took the pug. But when you cross them, of course, the females can't give birth because the birth canal just doesn't allow for it. Humans realize this pretty quickly and they learn cesarean section. So I could imagine a situation, although I don't tend to think like this. Today, I'm imagining a situation where homo sapiens and some other non-homo sapien human-ish. species, were having sex, sometimes getting pregnant, but the babies would always die because the birth canal and the structure of the pelvis wasn't. quite right to allow the head size through, which, you know, there are a lot of, I hear a lot of arguments that, you know, humans sort of optimized for just enough space so that the large brain humans, you know, we love to talk about how big our brains are, right? Could pass through, but no larger and not much smaller in most cases. One Speaker 2 (22:01) of the reasons that giving birth is one of the ways that women have died in our evolutionary history. Right. And Speaker 1 (22:06) cesarean sections, I probably have changed human evolution in that sense, as has. aseptic conditions and things like that. Absolutely. For me, Speaker 2 (22:14) my child was a cesarean birth. Right. Speaker 1 (22:16) So I like to think you would have survived. But I could imagine a mutation that was an adaptive mutation where suddenly this other species, which maybe had a smaller pelvis, a female could deliver this child live. The mother survived as well. And then that DNA propagates so that there are now humans. maybe it's been bred out but that there are or were humans walking around who are not completely homo sapien Or is it not possible? I Speaker 2 (22:45) don't know about what's known about hip size or anything like this, but it is true that humans and our archaic cousins, Neanderthals, interbred and that people walking around today have Neanderthal DNA. Two to Speaker 1 (22:57) 5%, you said. Speaker 2 (22:58) Two to 5%. What's interesting about that, and it touches a little bit on the adaptation component that you raised, is that I think most people or a lot of people have heard this number. We have two to 5 % Neanderthal DNA. Less well understood is that it's a different 2 % to 5%. Like the 2 % Neanderthal that is in my genome is different from the 2 % or maybe 5 % Neanderthal that's in your genome is different than the next person. So it could be Speaker 1 (23:25) heart, liver, skeleton, and spleen for me, and it could be some other constellation for you. Could Speaker 2 (23:31) be anything. And if we were to go around the world today and pick out all of the pieces of Neanderthal DNA that exist in humans today, we would put together more than 90%, possibly more than 95 % of the Neanderthal genome, just from people who are alive today. And that tells us that most of the Neanderthal genome was not maladaptive for people, that pretty much all of it could get passed on and live in healthy humans today. Interesting. We don't... know what happened in the other direction, right? We see Neanderthal bones and there hasn't really been any evidence of humans admins with Neanderthals. There has been evidence of hybrids between Neanderthals and Denisovans. This is really one of the most exciting things that ancient DNA has been able to contribute, I think, to understanding human disease and human medicine and what it means to be human. Because before we had the Neanderthal genome, if we wanted to know what in our DNA makes us human, we would have to compare all the humans that are alive today. with our closest living relative, which is a chimpanzee or a bonobo. So there's three to five million years of time between when we shared a common ancestor and a lot of change happens in three to five million years in your DNA. And some of it is useful. Some of it is what makes us human. And most of it is just not. It's just change because copying errors during... copying cells. And that's what happens. That's how we're different. Every child that's born has about 100 differences compared to their parents because of copying error in the process of making the sperm and making the eggs that made that kids. So when we got the Neanderthal genome, that 3 million to 5 million year long branch leading to us was shortened to 300,000 to 500,000 years by an order of magnitude. So now if we want to know what it is that makes us human, we have a much smaller list of mutations or variants that we can look at. And because we now know that 95%, say, of the Neanderthal genome exists in people today. We've narrowed that list down even further to that other 5%. What's going on in that 5 % of the genome where no living person has Neanderthal DNA? That is where the stuff that the baby had to have the human version in order for that baby to survive. That's where we look to see what it is that made Speaker 1 (25:52) us human. A few years back when 23andMe and these other companies started making genomics in humans easier and more affordable, a lot of guys... boast about Neanderthal DNA being vigor genes, whereas women try and downplay the amount of Neanderthal DNA that they have when they get their results. I found that interesting. Is there any evidence that the Neanderthal genes are, quote unquote, vigor genes, that they allow for more durability of human, male or female? Speaker 2 (26:21) It's an interesting question. If you just look at that 2 % to 5 % of Neanderthal DNA that we all have, most of it is not anything that is under selection. So you see it at about 3 % frequency or so in different populations. What is interesting is when a piece of Neanderthal DNA is suddenly much more common in a population of humans, because that would suggest I got some DNA from my Neanderthal ancestry, and that bit of DNA suddenly made me more fit. Because I had that bit of Neanderthal DNA, I was able to survive. and have more kids than everybody else. And so it increases in frequency compared to average. And this has been a really interesting thing to learn when you think about Neanderthal DNA. There are a couple of things that have come out. There are genes that are common in Latin American populations that come from Neanderthals that predispose to type 2 diabetes. There is another gene that I think was, again, in a Latin American population that makes people feel, I can't remember if it was more pain or less pain, but it did have to do with pain sensation. And I remember there was a trial of people in Colombia where they got to feel pain in some way. And there's a Neanderthal gene associated with this. But most of the really interesting ones have been in immune-related genes. During the pandemic, one of the first alleles that was discovered to be associated with negative risk or bad outcomes of COVID was a gene that came from So it's a Neanderthal derived gene that was at something like 50 % frequency. So way above the 3 % average frequency in Asian populations. And it made people more susceptible to the virus entering your lungs. Presumably, it only became that high frequency because it was protective against some other disease that was circulating in the past. But the trade-off of that is that it, of course, made them more susceptible to COVID. There was another Neanderthal associated allele. that was actually protective against COVID. So I think our ancestors have been subjected to different diseases and pandemics and things that have happened throughout life. And we see the traces of that in ancient DNA. We can now go into graveyards in Europe and actually isolate. plague from dirt and from bones from people who died of plague and look and see how their immune systems and genes have responded to exposure to things like this. It's really fascinating. Speaker 1 (28:39) Wow. My redhead friends like to claim that they have more Neanderthal and therefore more vigor and pain resistance. So I'm guessing the study probably said more pain resistance. We have pain experts on here that verify that indeed, on average, that redheads tend to require more anesthesia. on average. So that tracks. But were Neanderthals, were a lot of them gingers? Speaker 2 (29:03) Yes. This comes from studying an MC1R, a gene that's associated with the red melanin. Mammoths as well. They had, I mean, you can see mammoth, you can see mammoth mummies with the actual hair and you can see that they're kind of, I don't know if it's because they all bleach to red, but there definitely is some evidence from their genome that they had reddish colored hair. Interesting. Speaker 1 (29:22) Maybe we could just briefly talk about eye color. Is it true that all blue eyed people descended from a single blue-eyed human at one point. This almost sounds like some eugenics thing, but that's not why I'm asking. You also see a lot about how true green-eyed people are quite rare. Was there a time when the population of humans on Earth had a lot more green-eyed people? I Speaker 2 (29:41) think all of the colors, if you look at African populations, mostly it's like me, dark, dark eyes. I think that's... probably the ancestral state, but there are lots of different eye colors that have evolved. And I think they're selected for, I mean, people like things that are different and unique. And so people want a mate that has blue eyes instead of brown Speaker 1 (29:58) eyes. Speaker 2 (29:58) Do Speaker 1 (29:58) you really Speaker 2 (29:58) think that it Speaker 1 (29:59) was selected for at the level of mating? I think probably eye color Speaker 2 (30:01) was sexual selection. I don't know what other benefits blue eyes could have other than looking very, you know, stoic and cool as you're like trying to hunt down something on the... Oh, Speaker 1 (30:14) geneticists are so much fun because they're willing to just go there. I was going to ask you this question later, but I'll ask now because it relates to what we're on to now. You know, we tend to think of our lives in the time bin of our lives, you know, roughly 100 years if we're lucky, right? You know, at this stage of human evolution for about 100 years, maybe 80, maybe, you know, if we're fortunate, 90, 100. But as somebody who studies long periods of time and what's happened to our species and other species across long periods of time, I'm always curious about this. I know you have to make your coffee in the morning and do everything. you know, manage your life like anybody else in the today and in the week and in the month and in the year. But do you sit back and think of all the different tens and hundreds and thousands and millions of years that it could focus on? I'm going to focus at this time bin, right? It's an interesting way to live. Now, I'm just curious how you pick the problems that you choose to work on, because we'll talk about de-extinction, but you know, why the woolly mammoth? Why not like get the floor to... Panthers rebooted completely. Why not both? Why not both? Right. But in terms of just, you know, where to focus, like why bring back things from way back when, as opposed to, you know, maybe we could name a few species that disappeared in the last 200 years. I'm guessing there are quite a few. Yeah. You know, how do you pick? And when you're making that decision, what's guiding it? at the ethical level, what's guiding it at the practical level? Like what really are you trying to accomplish? Because the stuff about humans is fun place to play and put in the backdrop, we'll return to it. But your work's really focused on de-extinction. And like dinosaurs are one option, woolly mammoths are another. And, you know, just making sure that we don't lose any species that we've got right now also seems like a very, very important, indeed noble pursuit. Speaker 2 (32:04) Yes, that's a very complicated set of questions there. I think I'll start with what is motivating? And I think what's motivating is what drives the selection of the species. In fact, it's funny, I wrote a book a long time ago now called How to Clone a Mammoth. And the first chapter was how to pick a species. What are you going to do? How are you going to choose a species to bring back? And there are... technical, ethical, ecological, and social reasons to pick any of the species that you can. Technical, these are the easiest, right? We can't bring a dinosaur back to life because we don't have dinosaur DNA. The oldest DNA that we have ever recovered from a bone is from a mammoth bone. A mammoth's bone probably dates to around one to two million years ago. Speaker 1 (32:52) It's Speaker 2 (32:52) hard to know how old it is in that time range because there's not a really... clean way of dating something within that time range but it's old dinosaurs went extinct more than 66 million years ago so that's far outside of where we're going to get recoverable dna so that's Speaker 1 (33:05) because the skeletons just don't they're Speaker 2 (33:07) fossilized they've turned into rock right so there's Speaker 1 (33:10) no Shred of DNA left. Speaker 2 (33:12) Yeah. As soon as an organism dies, the DNA in its cells starts getting chopped up into smaller and smaller and smaller fragments until eventually there's nothing left. This is really by three processes. UV light. We know about this. It's why we wear sunscreen when we go outside. But the UV light hits your DNA and it actually breaks it. And when we're alive, we have proofreading enzymes that will come and fix your DNA so you don't get cancer every time you go outside. But that is an energy requiring process. process and after you die there's no more energy so the breaks from uv accumulate freezing and and thawing is water molecules expand and will physically break the dna fragment so that's bad for dna preservation and most importantly just microbial decay the fungi the bacteria that get into an organism when it's decaying and chew it up to transform that carbon and nitrogen into the next generation of organisms, right? And so that process is slower in some environments than others, exactly in the same way that your sandwich will rot faster if you leave it in the sun versus in the shelf versus in the fridge versus in the freezer. DNA will preserve for longer in the cold Arctic where things are rapidly buried in frozen dirt and they stay that way for a million years, like this mammoth bone that we were able to recover DNA from. But if you die in a very hot, wet, swampy place like Mauritius, where the dodo lived, it's another one of the species that we're working on, a colossal, very little chance you're going to be able to recover DNA from any of the fragments that are on Mauritius Island. And I have tried like hundreds of bones from Mauritius. We have a great dodo genome, but it's from a bird that went to Europe alive on a ship and is part of the collection at the Danish Speaker 1 (34:54) Museum of Natural History. So Speaker 2 (34:56) you have to have... a well-preserved sample that you can get DNA from. Ideally, many of them, because you want to know what are the DNA changes that made a mammoth a mammoth instead of another type of elephant, right? So many of them will help you to do that, but one is good enough to get some sort of template for what you're going to do. You probably should know what caused that species to go extinct in the first place so that you don't bring something back that... becomes the first species to be de-extinct and then the first species to be re-extinct. Or Speaker 1 (35:29) bring back something really nasty. knocks out a bunch of other species. Speaker 2 (35:33) Yeah, you have to