Huberman LabBringing Extinct Species Back to Life | Dr. Beth Shapiro
EVERY SPOKEN WORD
140 min read · 27,599 words- 0:00 – 2:35
Beth Shapiro
- BSDr. Beth Shapiro
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.
- AHAndrew Huberman
Mm.
- BSDr. Beth Shapiro
It is the same tools. It's the same technology.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
It's the same needs, and when we excite people with the idea of mammoths-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... 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.
- AHAndrew Huberman
Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. [Instrumental music] 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.
- 2:35 – 9:13
What is a Species?, Taxonomy, Bison
- AHAndrew Huberman
Dr. Beth Shapiro, welcome.
- BSDr. Beth Shapiro
Thank you.
- AHAndrew Huberman
Longtime fan of your work.
- BSDr. Beth Shapiro
Same.
- AHAndrew Huberman
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.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
I'm a big fan of mustelids, of which ferrets are. We're gonna 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 you think people might appreciate understanding about taxonomy and, like, a... Is my dog, as a bulldog mutt, really the same as a Chihuahua? Are they really the same species?
- BSDr. Beth Shapiro
Right. 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, a human concept. We have this incredible proclivity to want to put things into boxes so that we can talk about them.
- AHAndrew Huberman
Sure.
- BSDr. Beth Shapiro
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.
- AHAndrew Huberman
Kingdom, phylum, order, genus, spec- like, this kind of thing. Clade, you know? Yeah.
- BSDr. Beth Shapiro
That, no, that's the taxonomy, right?
- AHAndrew Huberman
Right. Yep.
- BSDr. Beth Shapiro
So we have, uh, Linnaeus-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... came up with this idea of doing taxonomy, right? So here's an interesting taxonomy story. I've, I've spent a lot of my career working on bison for unfortunate reasons probably or for fun reasons or whatever, but a lot of time working on bison. And bison were called buffalo. Buffalo, right? We think of American bison as buffalo. It's the same thing. It's the, 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 buff 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.
- AHAndrew Huberman
That's the Latin name, Bison bison bison?
- BSDr. Beth Shapiro
Bison bison bison.
- AHAndrew Huberman
It's almost as humorous as, I think it's Gorilla gorilla-
- BSDr. Beth Shapiro
Yes
- AHAndrew Huberman
... for the gorilla.
- BSDr. Beth Shapiro
Gorilla gorilla, and Llama llama. That's one of my favorites, too.
- AHAndrew Huberman
Love it.
- BSDr. Beth Shapiro
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 Mayr's, is the biological species concept, which says if they can breed and their offspring are fertile- then they're the same species.
- AHAndrew Huberman
Which seems like a good place to start.
- BSDr. Beth Shapiro
It's a good place to start.
- AHAndrew Huberman
Because even w- in my understanding from my fly biologist 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 because-
- BSDr. Beth Shapiro
Well, I beg to d- disagree there. I mean, if you've seen your dog try, your dog probably tries to mate anything it comes across [laughs] .
- AHAndrew Huberman
He just hit seven months. I've not seen him hump a single time. He's still intact.
- BSDr. Beth Shapiro
Okay.
- 9:13 – 12:38
Neanderthals, Denisovans, Homo Sapiens
- AHAndrew Huberman
us on this Neanderthal piece. I know this is a, a topic very close to home.
- BSDr. Beth Shapiro
[laughs] Yes.
- AHAndrew Huberman
Given that your husband works on these issues, and we can, maybe we'll get him on here separately, but-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... uh, feel free to steal his thunder in any way that, that you feel would-
- BSDr. Beth Shapiro
Uh, my husband, Ed Green, was part of Svante Pääbo'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, w- if we start there with what's going on with Neanderthals, is w- we now know based on studying DNA, both from Neanderthals that used to be alive and a different lineage of human called a Denisovan, we, we call it this, that was first isolated again by Svante Pääbo's research group from a tiny little finger bone that they found in a cave, Denisova 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 wanna 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.
- AHAndrew Huberman
Many questions about this. First of all, and try not to laugh, the silhouette diagram that we've seen of apes gradually-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... in sort of time sequence working their way to bipedal and upright, when we see that diagram, is that substantiated by the fossil record?
- BSDr. Beth Shapiro
It is, yes. Um, we know that the, 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, it's very fragmentary. O- one thing that's really been really fun about working in ancient DNA is the field of paleoanthropology is 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.
- AHAndrew Huberman
Hmm.
- BSDr. Beth Shapiro
What's brilliant about ancient DNA is that if I can find a little pinky bone in a cave in 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. [laughs]
- 12:38 – 15:27
Sponsors: Joovv & Eight Sleep
- AHAndrew Huberman
I would like to take a quick break and acknowledge one of our sponsors, Joovv. Joovv 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. These include faster muscle recovery, improved skin health, wound healing, improvements in acne, reduced pain and inflammation, improved mitochondrial function, and even improvements in vision. Nowadays, there are a lot of red light devices out there, but what sets Joovv lights apart and why they're my preferred red light therapy device is that they use clinically proven wavelengths. Meaning they use the specific wavelengths of red light, near-infrared, and infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv whole body panel about three to four times a week, usually for about 10 to 20 minutes per session, and I use the Joovv handheld light both at home and when I travel. If you would like to try Joovv, they're offering up to $400 off select products for listeners of this podcast. To learn more, visit Joovv, spelled J-O-O-V-V, .com/huberman. Again, that's J-O-O-V-V .com/huberman. 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 Eight Sleep, go to eightsleep.com/huberman to get up to $200 off their new Pod 6. Eight Sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com/huberman to save up to $200.
- 15:27 – 20:30
Hybrid Ancestry, “Grolar” Bears
- AHAndrew Huberman
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, you know, two different species, again, it's a nomenclature to some, 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.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
But you can get breeding across species and get reproductively-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... viable offspring. That, that has to be the way this happened, right?
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
It couldn't have just been through spontaneous mutations that-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... suddenly took animals from quadrupeds to bipeds.
- BSDr. Beth Shapiro
No, 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. Uh, uh, 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's it, it's in, maybe it's, you know, 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, 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. Uh, or it could be that nothing really has happened over a really long evolutionary time and admixture can happen.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
Humans 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-
- AHAndrew Huberman
Is that right?
- BSDr. Beth Shapiro
... in habitat. Yeah. They're called Grolar Bears or Pizzly Bears, depending on which direction.
- AHAndrew Huberman
Pizzly Bears.
- BSDr. Beth Shapiro
I know, they're terrible names, right? Well, you want a different name for this really cool bear.
- AHAndrew Huberman
Yeah, especially if you're a, a bear.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Yeah.
- BSDr. Beth Shapiro
But that's been happening throughout their evolutionary history. We can see this because using ancient DNA, we were able to go back. We found, um, 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 s- at some point, or that bear's descendants had hybridized with brown bears, and that DNA got passed around. And 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.
- AHAndrew Huberman
Wow.
- BSDr. Beth Shapiro
Yeah, so in that case, 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 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-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... so the presence of a male will call them to ovulate, 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 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 when 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-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... 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.
- 20:30 – 25:53
Homo Sapiens & Neanderthal Interbreeding, Genes; Denisovans
- AHAndrew Huberman
I'm gonna 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 bull mastiff and the pug. And this was an attempt to generate an animal with a short snout so it could clamp down for bull baiting-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... which fortunately is an illegal sport now, and to clamp down and not get shaken off by the bull very easily. Uh, 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.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
Humans realized this pretty quickly, and they learned 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-ho- Homo sapien human-ish species were h- 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 have optimized for just enough space so that the large-brained humans, you know, we love to talk about how big our brains are, right, could pass through, but no larger and, and not much smaller in most cases.
- BSDr. Beth Shapiro
One of the reasons that giving birth is one of the ways that women have died in our evolutionary history.
- AHAndrew Huberman
Right, right. And ce- and cesarean sections, I, probably have changed human evolution in that sense.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
A- as has a- aseptic, you know, conditions-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... and things like that. Um-
- BSDr. Beth Shapiro
Absolutely for me. My child was cesarean birth, so yeah. [laughs]
- AHAndrew Huberman
Right, so I like to think you would have survived anyway. But the, um, 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, the mother survived as well, and then that DNA, you know, 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-
- BSDr. Beth Shapiro
Well-
- AHAndrew Huberman
... not possible?
- BSDr. Beth Shapiro
I don't know about what's known about hip size or anything like this, but, but it is true that humans and our archaic cousins, Neanderthals, interbred, and that people walking around today have Neanderthal DNA. That-
- AHAndrew Huberman
2 to 5%, you said.
- BSDr. Beth Shapiro
2 to 5%. What's interesting about that, and it touches a little bit on the adaptation component that you, you raised, is that I think most people, or a lot of people, have heard this number. We have 2 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's.
- AHAndrew Huberman
So it could be heart, liver, skeleton, and, uh, spleen for me, and it could be some other constellation for you.
- BSDr. Beth Shapiro
Could 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.
- AHAndrew Huberman
Interesting.
- BSDr. Beth Shapiro
We don't know what happened in the other direction, right? We, we see Neanderthal bones and there hasn't really been any evidence of humans admixing 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, and some of it is what makes us human, and most of it is just Not. It's just changed 'cause 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 three million to five-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 wanna 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-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... in order for that baby to survive, that's where we look to see what it is that made us human.
- 25:53 – 30:17
Neanderthal Genes, Immunity, Red Hair; Eye Color
- AHAndrew Huberman
A few years back when 23andMe and these other, uh, companies started making genomics in humans easier and more affordable, a lot of guys boast about Neanderthal DNA-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... being vigor genes.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
Uh, whereas women try and downplay the amount of Neanderthal DNA that they have when they get their results.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
I found that interesting. Is there any evidence that the Neanderthal genes are, quote-unquote, v- vigor genes, that they allow for more durability of human, male or female?
- BSDr. Beth Shapiro
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 at, 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 Neanderthals, so it's a Neanderthal-derived gene that was at something like 50% frequency, so way above the 3%-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... average frequency in Asian populations, and it, it made people more susceptible to the virus entering your lungs. It 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, you know, made them more susceptible to COVID. There was another Neanderthal-associated allele that was actually protective against COVID.
- AHAndrew Huberman
Huh.
- BSDr. Beth Shapiro
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, in ancient DNA. We can now go into graveyards in Europe and, 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-
- AHAndrew Huberman
Wow
- BSDr. Beth Shapiro
... to things like this. It's really fascinating.
- AHAndrew Huberman
Wow.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
My redhead friends like to claim that they have more Neanderthal and therefore more vigor-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... and pain resistance, so I'm guessing the study probably said more pain resistance. It-
- BSDr. Beth Shapiro
Probably. Yeah. With the red hairs, true, yeah
- AHAndrew Huberman
... we've got pain experts on here that verify that indeed, on average, that redheads tend to require more, uh, anesthesia, on average.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
So that tracks, but were Neanderthals, uh, were a lot of them gingers?
- BSDr. Beth Shapiro
Yes. This comes from studying an MC1R, a gene that's associated with the red melanin. Mammoths as well, they had, uh... 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 bleached to red, but there definitely is a, um, yeah, some evidence from their genome that they had reddish-colored hair, yeah.
- AHAndrew Huberman
Interesting. 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?
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
This almost sounds like some eugenics thing, but that's not why I'm asking. [laughs]
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Um, you also see a lot about how true green-eyed people are, are quite rare. Was there a time when the population of humans on Earth had a lot more green-eyed people?
- BSDr. Beth Shapiro
I think all of the colors, if you, if you look at, um, 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 eyes.
- 30:17 – 38:08
De-Extinction, Species Selection, Woolly Mammoths
- AHAndrew Huberman
go there. I was gonna ask you this question later, uh, but I'll ask now because it relates to what we're onto now. You know, we tend to think about our lives in, 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-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... we live for about 100 years, maybe 80, maybe, you know, if we're fortunate-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... 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 everyth- and, you know, manage your life like anybody else in, in the today, and in the week, and in the month, and in the year, but do you, do you sit back and think of all the different tens and hundreds and thousands and millions of years that you could focus on, I'm gonna focus at this time been, right? It's a, it's an interesting way to live, and I'm just curious how you picked the problems that you choose to work on. 'Cause we'll talk about de-extinction, but, you know, why the woolly mammoth? Why not, like, get the Florida Panthers rebooted-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... um, completely? Maybe you already have.
- BSDr. Beth Shapiro
Why not both?
- AHAndrew Huberman
Why not both?
- BSDr. Beth Shapiro
Yes.
- AHAndrew Huberman
Right. But in terms of just, you know, where to focus, what... Like, why bring back things from way back when, as opposed to, you know, uh, could- maybe we could name a few species that, uh, disappeared in the last 200 years.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
I'm guessing there are quite a few.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
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, what really are you trying to accomplish? 'Cause 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.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
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.
- BSDr. Beth Shapiro
Yes. Uh, this... That's a very complicated set of questions there. Um, 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 w- I wrote a book a, a long time ago now, called How to Clone a Mammoth, and the first chapter was how to pick a species. What are you gonna do? How are you gonna 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? W- 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.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
It's hard to know how old it is in that time range, 'cause 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 gonna get recoverable DNA. So-
- AHAndrew Huberman
And that's because the skeletons just don't, uh-
- BSDr. Beth Shapiro
They're fossilized. They've turned into rock, right? So-
- AHAndrew Huberman
There's, there's no shred of DNA left, so to speak.
- BSDr. Beth Shapiro
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, 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 at Colossal, very little chance you're gonna 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 Museum of Natural History. So 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 gonna 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.
- AHAndrew Huberman
Or bring back something really nasty that knocks out a bunch of other species.
- BSDr. Beth Shapiro
Yeah. You have to understand the role that that animal played in the ecosystem and whether that niche is still available. I mean, ecosystems don't live in a vacuum just waiting for something to come back, and in some cases, there's a real ecological driver. For the species that we're focusing on, we feel like there is a real ecological role for these species to play, that these ecosystems are destabilized because of extinction, and by bringing back these key ecological interactions, we can make those ecosystems more robust and more resilient in the face of all the crap that people are always throwing at our natural ecosystems.
- AHAndrew Huberman
Could you give me an example of, of that? So if you were to bring back woolly mammoths, I'm guessing that's not gonna save the Amazon forest, but what-
- BSDr. Beth Shapiro
No
- AHAndrew Huberman
... what, what probably is gonna do something useful based on what you just said?
- BSDr. Beth Shapiro
Yeah.
- 38:08 – 39:21
Sponsor: AG1
- AHAndrew Huberman
I'd like to take a quick break and acknowledge our sponsor, AG1. I'm excited to share that AG1 has just launched their newest formulation, AG1 Pro. AG1 Pro takes the clinically backed AG1 formula, which is a blend of vitamins, minerals, probiotics, and adaptogens, and adds three important new ingredients: creatine monohydrate, calcium HMB, and zinc carnosine. Each serving has five grams of creatine monohydrate to support muscle strength and performance, as well as brain health, calcium HMB to support muscle recovery and reduce muscle breakdown, and zinc carnosine to support and improve the lining of your gut. All three of these ingredients have compelling science to support them, and therefore, I love seeing them added to the existing AG1 formula. As most of you know, I've been taking AG1 every day for nearly 14 years now. I started taking it long before I even knew what a podcast was. It's a great product, and it's now made even better with the new AG1 Pro formula. If you would like to try AG1 Pro, you can go to drinkag1.com/huberman to get a special offer. AG1 is giving away a free bottle of omega-3 coenzyme Q10 with your first subscription. Again, go to drinkag1.com/huberman to get a free bottle of omega-3 coenzyme Q10 with your first AG1 subscription.
- 39:21 – 47:40
Bird De-Extinction, Dodo; Reproduction & Genes
- AHAndrew Huberman
Okay, so you're picking... Look, you don't have to pick a species, but you gotta pick something to f- you know, two or three.
- BSDr. Beth Shapiro
Right, right.
- AHAndrew Huberman
I, I can't say, like, we're gonna bring back everything from a given era. So I mean-
- BSDr. Beth Shapiro
So we did technical, ethical-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... ecological. I think the, another answer is what is going to make an impact, right?
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
When I joined Colossal, we didn't have a bird program, but I really wanted there to be a bird de-extinction program because th- all of the tools that we are developing for de-extinction are the same tools that we can use to use synthetic biology to modify the genomes of living species and help them avoid becoming extinct.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And so the kit that we're building from multiplex genome engineering to cellular rejuvenation to IPS cell technologies for wild animals to even learning the link between particular letters of the DNA sequence and what those letters actually do to cause an animal to look the way that it does, right? All of that is applicable across the board. So the stack that we're building for de-extinction, for synthetic biology stack applies to synthetic biology for conservation. So when I joined Colossal and there wasn't a bird program, they had launched the mammoth program, which is a placental mammal, and the thylacine program, or Tasmanian tiger, that's a marsupial mammal. But birds are among the most endangered species on the planet, and it is not possible to clone birds using somatic cell nuclear transfer, the process that most famously brought us Dolly the sheep, because we don't have access to the egg cells at the right stage. So while that process is really pivotal and integral to our mammoth and thylacine, any other mammalian project, it's just not possible to use it for birds. And so I wanted a program that was going to help us develop technologies for birds. So why did we pick the dodo compared to an- any other bird for the first one?
- AHAndrew Huberman
Cool beak.
- BSDr. Beth Shapiro
It comes down to that, which I also think is a really important part of talking about this project, and it's the idea of awe, of being excited about something. We get kids drawing animals that... Drawing mammoths and thylacines and dodos and sending them to us all the time. Ben has put them in frames up around... Some of them are good.
- AHAndrew Huberman
The dodo with its sort of rounded top beak also, and the way the eyes are typically drawn, it also has a kind of cartoonish, friendly, Toucan Sam type of look.
- BSDr. Beth Shapiro
Well, it was in Alice in Wonderland. Most of what we know about the dodo is from cartoonish drawings of this animal. There are some, and of course there's skeletons that we can piece together using the many, many bones in Mauritius that do not have any DNA in them, based on my very best tries.
- AHAndrew Huberman
You didn't choose to bring back, like, a 75-foot long python, thank goodness.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Oh, but there may be virtue in doing that, right?
- BSDr. Beth Shapiro
There might be, although I think there are plenty of pythons in Florida Everglades right now without doing anything.
- AHAndrew Huberman
I, I'm not a snake fan. No disrespect to the snake lovers. But c- talk about, uh, bird developmental genetics for a second. Not to scare anyone away, but hang in there. A few years ago, I saw something that, um, two female condors can reproduce.
- BSDr. Beth Shapiro
Crazy, right?
- AHAndrew Huberman
Right? And this of course for, uh-
- BSDr. Beth Shapiro
It actually wasn't two female condors reproducing. It was one female condor-
- AHAndrew Huberman
One female condor
- BSDr. Beth Shapiro
... just having an egg all on her own.
- AHAndrew Huberman
Yeah, and because of the sociopolitical implications, it's got people in where we're from-
- BSDr. Beth Shapiro
They said-
- AHAndrew Huberman
... Northern California pretty excited. They were like, "Okay, we don't need men after all," right?
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
That was the, that's always, that was the, you know-
- BSDr. Beth Shapiro
That's funny, 'cause what I heard was life finds a way.
- 47:40 – 54:49
Development Biology, Woolly Mammoth, Elephants
- AHAndrew Huberman
talk about that. And before we do that, we should probably do a brief developmental neurobiology lesson. You beautifully told us what meiosis is. You know, sperm or egg, you have 20, well, in humans it's 23 chromosomes, so you only have half so that they can meet in conception and then start to divide and, uh, create more cells that, uh, become the embryo, right?
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
And so in these other species, I guess you know how many chromosomes there are, and I w- must use the woolly mammoth or the, 'cause it's a fun one.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
And birds are complicated.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
As a developmental neurobiologist in my past, the bird stuff gets tricky, reptile stuff-
- BSDr. Beth Shapiro
Birds are tricky, and there's-
- AHAndrew Huberman
They're really tricky
- BSDr. Beth Shapiro
... some birds are trickier than others. Uh, I did not know until I joined Colossal that there are some birds that have a, what's called a germline-restricted chromosome, which doesn't exist in any of their cells except for the germline. And-
- AHAndrew Huberman
Germline are the s- uh, sperm and eggs
- BSDr. Beth Shapiro
... sperm and eggs.
- AHAndrew Huberman
Yeah.
- BSDr. Beth Shapiro
And it comes into being, this chromosome, just in the germline, and then it disappears.
- AHAndrew Huberman
Wow.
- BSDr. Beth Shapiro
I know. Biology's amazing.
- AHAndrew Huberman
Yeah. Yeah. Birds-
- BSDr. Beth Shapiro
Like birds have these, like, mini microchromosomes that are a pain to assemble, and if you're sequencing DNA from-
- AHAndrew Huberman
Yeah
- BSDr. Beth Shapiro
... an extinct species where the DNA fragments are really short and you have to do it by taking each one of those really short fragments and trying to figure out where on a whole genome it goes best, on a computer, we don't actually do it with our, with, like, uh, tweezers or anything like that. But, uh...
- AHAndrew Huberman
Yeah. The birds are really cool animals, but they, from reproductive biology standpoint, it's, it's tricky. So with the woolly mammoth was a mammal
- BSDr. Beth Shapiro
Yes
- AHAndrew Huberman
Right. Okay, and you know that because, I mean, people can say, "Well, duh," 'cause people normally think, "Oh, it has fur. It must be a mammal."
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
But that is not necessarily true, right? You have monotremes and all this other stuff. So you know it's a mammal because there's evidence of lactation? How are you deeming it a mammal?
- BSDr. Beth Shapiro
Using its genome.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
So we've been able to sequence whole genome sequences, high-quality whole genome sequence with sequences from multiple mammoths that date to the last million and a half years, and we can assemble those genome sequences using a computer, and then we compare them to other animals that are alive today, and we know that the closest living relative of a mammoth is an Asian elephant. And in fact, mammoths and Asian elephants are more closely related to each other than Asian elephants are to African elephants. So mammoths are nested within the elephant family, most closely related to Asian elephants.
- AHAndrew Huberman
Okay, so if you get the, the sequence of DNA from a mammoth, so you know, okay, this is the complete genome. And I think a lot of people probably don't realize that your complete genome is represented in most all of your cells. There are rare exceptions. It's just that not all those genes are expressed, which is why you get a hair cell versus skin cell versus heart cell and so on.
- BSDr. Beth Shapiro
That's the epigenome.
- 54:49 – 1:03:26
Dire Wolf, Synthetic Biology, Ethics
- AHAndrew Huberman
When you mentioned, um, species nomenclature gatekeeping, I have a feeling this is based on the publicity around the dire wolf.
- BSDr. Beth Shapiro
[laughs] Yes.
- AHAndrew Huberman
Okay. I just, I, I like to just address things very directly. I wanna be very clear, I'm not arguing for species gatekeeping here.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Uh, that's not what I do. I have... I own a mutt, uh, after all.
- BSDr. Beth Shapiro
It's not even that. It's, it's that, um, it somehow this idea of what we should call it based on this very specific definition of you can only call it this if it's some threshold-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... genetic similarity, is noise. It's not an important part of the conversation. I mean, it's a part of the conversation, and it's one that we can have, but if people don't wanna call it a dire wolf, just don't, right?
- AHAndrew Huberman
Yeah.
- BSDr. Beth Shapiro
Like [laughs]
- AHAndrew Huberman
Well, I think, like, like all things media and Hollywood, you know, the... I think Jurassic Park did an amazing service to science and the excitement around these concepts, but probably did a disservice as well by embedding in people's minds that the idea is to bring back the, the exact same animal.
- BSDr. Beth Shapiro
But didn't-
- AHAndrew Huberman
Yeah
- BSDr. Beth Shapiro
... we just say that these dinosaurs were some dinosaur DNA and a whole bunch of frog DNA?
- AHAndrew Huberman
Right.
- BSDr. Beth Shapiro
Nobody looks at them and goes-
- AHAndrew Huberman
Right
- BSDr. Beth Shapiro
... "No, they're not a dinosaur." [laughs]
- AHAndrew Huberman
Well, you're a scientist, and I am too. Actually, the, the... It's funny that you, you mention this because my dad's a theoretical physicist. He was involved in chaos theory. He's been a guest on the podcast. I remember when Jurassic Park came out, he didn't dislike it, but the part where he kind of rolled his eyes was there's a description of chaos theory in there and what it means, and in Hollywood, they love to use the example of, like, a butterfly flaps its wings in Patagonia, and then this thing happens in the, to the barista in, in Brooklyn, you know? And people like to bridge those concepts, and they... Oh, that's so cool. Like, so it's, it's, it's sticky-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... as we say, but that's... But he, he was rolling his eyes. He's like, "Okay, that's not how these things work."
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
And so for people that are experts in the area, it can be a little bit grading at times. But the public, I think, is open, right? In my experience in doing what I do is that the public, if they just have the knowledge in hand-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... and the way you described it, great so-
- BSDr. Beth Shapiro
So our dire wolves-
- AHAndrew Huberman
Yeah
- BSDr. Beth Shapiro
... they have 20 edits that we picked.
- AHAndrew Huberman
Okay.
- BSDr. Beth Shapiro
Um, and we w- 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. If it looks like a dire wolf and it's able to fill the niche of a dire wolf, I'm happy to call it a dire wolf.
- 1:03:26 – 1:09:22
De-Extinction, Ecology, Conservation, Ethics
- AHAndrew Huberman
So you have these three dire wolves. They're not mating. Is the plan to make more of them, to mate them? What's, what's the ultimate goal and intermediate goal?
- BSDr. Beth Shapiro
We will have another pack-
- AHAndrew Huberman
Okay
- BSDr. Beth Shapiro
... so that hopefully they will all be born more of them at the same time so that... And that's the plan eventually. It's not our priority right now. We're working on other species, but what we'd like to do is have another pack in the space where we are so we can really better understand the impact of the animals on the ecosystem.
- AHAndrew Huberman
Hmm.
- BSDr. Beth Shapiro
This is really the next rational, logical step in any de-extinction project. I often hear rumors, like, "What are you doing? You're just gonna take, get an elephant and, uh, make a mammoth and just release it into Alaska?" And you're like, "No."
- AHAndrew Huberman
No. [laughs]
- BSDr. Beth Shapiro
Um, first of all, no, 'cause it's gonna be so hard to make that first mammoth that I'm going to want to make sure that it is safe-
- AHAndrew Huberman
Right
- BSDr. Beth Shapiro
... and cared for and has access to-
- AHAndrew Huberman
Right
- BSDr. Beth Shapiro
... all the food that they need.
- AHAndrew Huberman
Well, this is the Jurassic Park thing again.
- BSDr. Beth Shapiro
[laughs] Right.
- AHAndrew Huberman
It's that they break out, right?
- BSDr. Beth Shapiro
But also, you know, you can't do that. We exist in the rel- regulatory environment of anywhere that these animals are. It's, it's not that we're some crazy scientists on an island like in Jurassic Park. You know, we, we work here. We have IACUC protocols, and, um, if you're doing anything that is releasing an animal outside, you're under the regulatory purview of a whole bunch of different agencies. I don't know if you saw, but the very first gene-edited organism created specifically for the purposes of conservation ecosystem restoration was deregulated by the USDA this week. It's the American chestnut tree.
- AHAndrew Huberman
Hmm.
- BSDr. Beth Shapiro
And a challenge with any of these genetically modified organisms that we have, which we're creating, synthetic biology uses a tool to make these things better. The chestnut tree is one of these stories, like the passenger pigeon, where the American chestnut was the most prolific tree across the eastern forests of North America, all the way through North America, until the early part of the 20th century when a disease was introduced, believed to be on an import of a Chinese chestnut tree, that caused a fungus to get into these trees, and they all died. But it took a decade, and a billion trees died.
- AHAndrew Huberman
This scares me for a variety of reasons. A few years ago, this would be 2016, '17, I got this strange envelope in the mail-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... to my residence. Do you know about this?
- BSDr. Beth Shapiro
No, [laughs] but I'm scared.
- AHAndrew Huberman
So there, there was a... So I was living in the East Bay, California, and I get this envelope, and it contains a little kind of like, looks like a small quarter-sized plastic, like, container, just thin, an envelope, and it had a little note, and it said, "Free seeds for gardening."
- BSDr. Beth Shapiro
Oh.
- AHAndrew Huberman
And I was like, "This is really odd," and I started, you know, fishing around on the Internet. Turns out the idea was that massive amounts of seeds were being shipped from China and sent here. Now, this isn't a conspiracy, right? Like, if you look at this, there are these, this sort of attempt to just kind of, like, put new populations of plants, and maybe it was all benevolent. And my friends, actually, one of whom is down at Santa Cruz, yeah, I know some plant biologists, they were like, "Whatever you do, do not put that into the ground outside because these things travel. Birds eat them. Birds poop, and then stuff gets, grows, and this is how you can decimate important populations of-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... trees and plants." It was the first time I really thought about vegetation-on-vegetation warfare. Is that what is actually what was happening? Is, was this the Chinese trying to do this? We don't know. But what is very important is that anytime you plant something, you actually want to talk to the people who understand how different ecosystems of plants coexist, in the same way that you wouldn't put your wolves out into the, you know, into the dog park.
- BSDr. Beth Shapiro
I wouldn't put the wolves out because if, if we released dire wolves, they would compete with gray wolves, and gray wolves are already having enough trouble trying to find a way to survive. And so there's no need, there's no ecological need to release gray wolves into the habitat. And so we can use them to study these. But if you think about what you just said, right? I, I think people, we as a lineage, have been messing with the evolution and, of the stuff around us for-
- AHAndrew Huberman
Oh, definitely
- BSDr. Beth Shapiro
... as long as we've existed, right?
- 1:09:22 – 1:15:45
Ecosystem Resilience, Thylacine; Preventing Extinction, Quolls
- AHAndrew Huberman
saying. It, it touches on an important theme that we've certainly never discussed on this podcast, but is very relevant to today's discussion and that people should think about, which is, you know, who gets to decide?
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
It's interesting 'cause there's both a kind of like massive ego inserted into the notion that, like, we know best about everything in-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... including the other, all the other species of plants and animals. That's obviously not true. But also that we don't have anything to contribute in terms of our own evolution that is... I mean, look, here you're a human being bringing back species of past, and some people might think scary, other people might think fantastic. I think why it's hard for people to wrap their head around these things and they default to thinking about, oh, it was better in the past, is because, A, most pe- people never experienced that.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
They have no concept. I think there's a great book that I had to read years ago called, uh, The Good Old Days Were Terrible, about we hear the good old days, and you hear about all, like, the dysentery, the lack of antibiotics. Like, but we tend to look back and say, "Oh, that was... It must have been so nice back then, everything bucolic and beautiful," and you forget all the, the, the dark side of that.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
But the other one is that we don't have a window into the future.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
And so, you know, I went to school in Santa Barbara, and one of the first things you learn there is that there are all these species of fox that are out on the, the Anacapa Island and, and Santa Rosa Island and all these islands that, that the Chumash brought out there on boats. But no one says they don't belong there. They say there's this incredible biodiversity out there, which is why it's protected, why we don't have, you know, a lot of tourists walking around out there. We wanna protect that. But humans brought those out. But the fact that it was Native Americans and it was, and it was some time ago leads to our percept like it was good, right?
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
And so the idea that we would remove them, no, we need to protect them. And that makes total sense to me, but it's a default psychology that I think is driving a lot of the, quote-unquote, "ethical conversations" around this-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... because we don't have a window into the future. So let's say these dire wolves, you make more of them. I can get totally on board the idea that then there are wild lands that they are roaming, that, that they're serving other populations of animals and plants. There's new interactions that are, that are benevolent interactions-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... that are pro-evolution as opposed to devolution. I think the challenge for people is we don't know what that looks like, the, and it feels like there m- there are too many variables to understand. So I'm just wondering how you wrap your head around that when you're talking to people about what you do and, and when you're thinking about what you do.
- BSDr. Beth Shapiro
I'm thinking in terms of helping ecosystems to become more resilient.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
We know, for example, because of what happened in Yellowstone, the impact that restoring the top predator of an ecosystem that had been removed can have. The gray wolves that were reintroduced into Yellowstone, the population of animals that they ate had become too large-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... and they had eaten away at all of the shrubbery. And so putting the gray wolves back in Yellowstone cascaded all the way down that ecosystem ladder to changing the way the rivers were flowing because the plants were growing back now along the edges of the rivers. The thylacine, which is the Tasmanian tiger, this is the second species that Colossal declared as one of our de-extinction targets, um, the thylacine was the top predator in Tasmania, and Tasmania today has problems because that top predator is missing. Have you heard about or seen the awful pictures of the Tasmanian devil facial tumor disease?
- AHAndrew Huberman
Yeah, this came up, um, on a few podcasts ago because we had Jared Rutter, who's a, another Hughes, uh, biologist. We're some mitochondria, and we're talking about there are no transmissible cancers, but these Tasmanian devils, um, have wound-induced cancer-like, uh- problems. So they fight, they scratch each other up, they get cancers, and th- that population is suffering as a consequence.
- BSDr. Beth Shapiro
And they're so closely related to each other that they can pass them between each other.
- AHAndrew Huberman
Oh, so it's the genetic similarity that-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... allows that to happen.
- BSDr. Beth Shapiro
The point is that I... Yes, this is terrible, but, uh-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... if we had had the top predators, those sick individuals would've been weeded out of that population, and we might not have this problem. So you can see restoring that ecosystem. And also, I'll get back to, 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.
- 1:15:45 – 1:17:23
Sponsor: Function
- AHAndrew Huberman
Mm-hmm. I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot of your bodily health. This snapshot gives you insights into your heart health, your hormone health, autoimmune function, nutrient levels, and much more. They've also recently added access to advanced MRI and CT scans. Function not only provides testing of over 160 biomarkers key to your physical and mental health, it also analyzes these results and provides recommendations for improving your health from top doctors. For example, in a recent test with Function, I learned that some of my blood lipids were slightly out of range. As a result, I decided to start supplementing with nattokinase, which can naturally help reduce LDL cholesterol, and it did. In a follow-up test, I could confirm that this strategy worked. My blood lipids are now back exactly where I want them. Comprehensive lab testing of the sort that Function offers is just so important for health. I mean, how else are you gonna know what's going on under the hood? And while I've been doing blood work for years, it used to be time-consuming, complicated, and expensive. In fact, I used to spend thousands of dollars per year trying to get this kind of data, and the data, frankly, were not all that good. But now with Function, it's extremely easy and affordable. A Function membership is only a dollar a day, $365 a year. And if you think about the information it provides and the health challenges it helps you avoid and the proactive things that it can do for you to enhance your health, I truly look at it as a savings. To learn more, visit functionhealth.com/huberman and use the code Huberman for a $50 credit towards your membership. Again, that's functionhealth.com/huberman.
- 1:17:23 – 1:25:50
Modeling Ecological Impact, Mosquitoes, Gene Drives; Panthers
- AHAndrew Huberman
As someone who does a lot of public science health education interaction, I... There, there are a couple things that get the public really worried and that they need reassurance on. Honestly, I think it dates back to the pandemic.
- BSDr. Beth Shapiro
Hmm.
- AHAndrew Huberman
There's a lot of distrust about scientists. There is this belief that some scientists are only concerned with themselves.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
It's an important myth, in my opinion, to dispel the idea that most scientists are not w- what I believe them to be, which is they're trying very hard to get answers right, to do good for the world, including other species, and it, they're not so careerist that they're willing to overlook that. Independent of the r- IRB boards and the thing that, the, the, the constraints that force them to, to do that, but th- that is the era we're living in, right? So I think that some people think more now in terms of, you know, scientists are, like, doing stuff 'cause they can. This has parallel conversations about AI, where people are thinking like, "Hey," like, "have we really thought this one through?" And people are sc- are scared. But I totally agree with, with what you're saying, and I wanna talk about two species to try and highlight this and how it can be done right, because I, I think it's clear that you're trying to do this right, which means for the, the best possible outcomes for humans and other species. And the first are mosquitoes.
- BSDr. Beth Shapiro
Hmm.
- AHAndrew Huberman
And the second are humans. Most people don't care about mosquitoes, but some years ago I started paying attention to mosquitoes because your very own Howard Hughes director now, I think Leslie Vosshall, works on the olfactory system of mosquitoes and other insects, and turns out bugs find mates and find things to suck blood from and et cetera by odors.
- BSDr. Beth Shapiro
Uh-huh.
- AHAndrew Huberman
And pheromones, but odors. And so there w- this idea, oh, mosquitoes have malaria. This wasn't Leslie's idea, but it was like Um, mosquitoes have malaria. Let's just get rid of all the, the mosquitoes.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
And the biologists were like, "No, you can't do that 'cause then the birds are gonna suffer-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... 'cause they eat the mosquitoes," and on and on and on. I mean, this stuff can really domino, and like, it sounds like a great idea. It's a terrible idea. Or let's just make mosquitoes that can't reproduce. That's a great way to do it, right? Or let's just do half of them, right? There were these ideas just kinda thrown out there that with genetics you can do that. You just release a few of these little suckers into the wild, and there is the potential that they mate and proliferate, and just enough to eradicate a population or half a population. It's harder to do than that. So people didn't know this was, like, being explored, but smart people put the brakes on it. So let's talk about mosquitoes. Like, it, they clearly carry pathogens that harm people, but they're also important for ecosystems, vitally important for certain ecosystems. So how do you think about plucking out a node in an ecosystem, like a species, or introducing a, a species back into an ecosystem, and thinking about the ramifications? It's hard to model behavior in one species, let alone interactions between species. How do you wrap your head around that? With the... Maybe the mosquito would be a, I hope, a simple example of this.
- BSDr. Beth Shapiro
Mosquitoes are a hard one, and I think that they do cause a lot of death and disease, but not all mosquitoes. So the, you know, only certain species of mosquitoes carry malaria and dengue and other diseases that are known to affect people. And also, those mosquitoes have much higher population density because of the way that people have built our towns than they would have had in natural ecosystems.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
So for something like a mosquito that is extremely overpopulated and carrying a devastating disease, I would think that there actually is reason to think that it is safe in an ecosystem to at least bring that population back down to a size that it would have been in a natural ecosystem. And a lot of problem with mosquitoes is because people leave, uh, just tubs of water or water that isn't circulating out, and they lay a billion eggs, and then you have many more mosquitoes. That's not true in the Arctic. In the Arctic, there's a bazillion mosquitoes and no people, and it's really miserable, but, uh, I've spent a lot of time in my life in the Arctic. [laughs]
- AHAndrew Huberman
Yeah, I heard you describing that elsewhere, and it sounds horrible. So I do not like mosquitoes. I don't like mosquito bites, and I get it. Like, at first blush, I'm like, "Get rid of all the mosquitoes," but it's a lot more complicated than that.
- BSDr. Beth Shapiro
Or maybe engineer mosquitoes that they can't carry the disease rather than engineer the mosquitoes to be dead. I mean, there are ways that I think we can use synthetic biology, and gene drives is the thing you were getting at, where you release something that is created by a synthetic drive into the wild, and then it passes on to the next generation.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
I actually think that gene drives are an incredibly powerful way that we have at our fingertips where, with the appropriate safety measures and care in place, we should think about how we might deploy these tools. You can make a gene drive so it only lasts for a fixed number of generations, and also because they tend not to make things reproduce, there is incredibly strong natural selection against them. Uh, anything that breaks a gene drive and lets something reproduce is gonna be favored in a population.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
Right? Um, so gene drives are gonna be difficult to get to persist, and there are many switches that we could build into them to make them last for a short period of time, but there are some species that have taken over. Uh, you talk about your plants that you got. In, in this part of the world there's cheatgrass everywhere, and it's highly flammable, and it grows alongside the roads, and it's Mediterranean in origin. And the only way we are ever going to get the cheatgrass down enough to be able to let the native California grasses come back is if we get rid of the cheatgrasses for a few generations. And, and-
- AHAndrew Huberman
Do you think this is one of the reasons there's so many fires?
- BSDr. Beth Shapiro
They're very flammable, and they also don't have very, um, deep roots. So in California it's very dry, right? Uh, California native grasses have much deeper roots, and so they stay green longer, so they're sequestering carbon, and they're not as flammable for longer into the season. These, these shallow-rooted Mediterranean grasses dry out super quickly, so as soon as it's fire season, like it is now, they're ready to go, right? And it's not just here. It's all across the western part of North America, and this is a problem, and it's a problem 'cause it causes, uh, huge amounts of damage to forest ecosystems, huge amounts of property damage when fires take off, and they're out-competing these grasses. This is a situation where I would say let's think about how we might safely deploy something like a gene drive that can remove something or at least tamp something down enough to allow that ecosystem to become again, once again, more robust and resilient. As far as, you know, what do we think about adding things back into an ecosystem, this is one of the reasons that every de-extinction project or every species translocation project is staged and thoughtful. When people moved Texas panthers into Florida in the mid-1990s to try to stop Florida panthers from becoming extinct, they had developed crooked tails and cowlicks and-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... cryptorchidism. Their testicles didn't descend, and they were going to become extinct. This was a inbreeding depression. There were only a few individuals, so they only bred with individuals they were related to. There was no choice. You bring in the Texas panthers, and the panthers recovered. All of these diseases disappeared for a short period. Now they're inbreeding again because the population is cut off from Texas, and so they'll have to keep doing it. We have to be the stewards of these ecosystems that we're creating, but that's in our power. We can do a ton of analyses about potential risks and rewards of what might happen when we modify an ecosystem, and we do it all the time.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
Sometimes to good ends and sometimes to bad ends.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
What we can't do, and I think this is sometimes where the conversation gets lost, is if you look around, we see habitats around the planet that are suffering because of changes that people have made. Within those habitats, there are species that are teetering at the edge of extinction, and the only strategy that they have to survive is natural selection, evolution and natural selection. The rate of change of these ecosystems is too fast for that to work. If we say These technologies that we have, whether it's translocations or assisted reproduction or genetic modification and synthetic biology and de-extinction, if we say that those technologies are too risky, we are accepting the outcome of doing nothing, which is also a decision. And I think that's where a lot of times the conversation gets lost. Doing nothing is not not deciding. Doing nothing is saying we accept the fact that we are going to have a future that is less bio diverse than the present.
- 1:25:50 – 1:29:13
Advisory Panels, Synthetic Biology Education
- AHAndrew Huberman
It's amazing how people are perfectly happy to allow the negative default outcome to emerge even though it's the consequence of humans, but they are wary of humans intervening to a potentially better outcome. I think it gets back to this issue of trust in scientists, and it also raises the question of who decides. I'm very opinionated about this when it comes to public health policy. I think what, what the pandemic taught us, regardless of where people sat on vaccines and lockdowns, if nothing else, it taught us something absolutely essential, which is you can't have one person be the spokesperson.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
People need to hear from a group, including the dissenters in that group, and why they arrived at a particular decision.
- BSDr. Beth Shapiro
I should be clear. For all of the species that we're working on, we have advisory panels that are built from local people. We have the Tasmanian advisory panel that has politicians and people who grow forests to log them and people who work with the animals and people who are scientists and conservation biologists, and we have regular meetings with all of our different advisory groups-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... to talk about what the future might look like well before we have a thylacine to be able to, to release anywhere. Our moa project is led by the Ngāi Tahu Research Centre in South Island of New Zealand, and these Maori people are the people who will be the long-term stewards of the moa, and the decision about how many to make, which moa to make, where to release them, how to release them-
- AHAndrew Huberman
Right
- BSDr. Beth Shapiro
... it's, it's their decision, um, in consultation with other people who will be impacted by this, and I think that's really important. The other thing that I think we do well is this, right? I mean, I am not a scientist hiding up in an ivory tower somewhere. I'm here talking to you and talking to as many people as I can to tell people all about what we're... We even get yelled at for this. Why is Colossal always talking about what Colossal's doing? Well, would you rather we not tell you? I mean...
- AHAndrew Huberman
I think the education piece is the critical piece. I think it's great that-
- BSDr. Beth Shapiro
But it's also hard-
- AHAndrew Huberman
... that Colossal is doing this.
- BSDr. Beth Shapiro
I mean, it is true. I, I think we are all desperate for... When the dire wolf story broke and there was a small subset of scientists who were just yelling at me that I wasn't allowed to call it a dire wolf, and there are a bunch of people who were like, "Wow, I can't believe you learned from a bone and actually used the tools of synthetic biology to engineer extinct traits into a living animal, and now you have living dire wolves," right?
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And there were people who were scared of it and people who loved it, and there were a bunch of people who said the word extinction and synthetic biology for the very first time in their lives. And I got emails from my colleagues at universities who said the undergraduates were coming into their ecology classes and their sociology classes, their anthropology classes. Some of them were mad and some of them were excited, but they were talking about it.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And they were talking about it as if they had some agency in the world that they were inheriting.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And we hear that from middle schoolers and high schoolers, and I think that is really something tremendous about what we're doing. People need to feel excited and positive, and they need to feel awe. And when I saw the dire wolves for the first time, that's what I felt is genuine awe, right? And there's something about that that just makes the world a better place. It makes people happier and healthier. And I love that I get to talk about it and do this hard science, like really hard science, with a bunch of smart people every day.
- 1:29:13 – 1:38:25
Genetic Selection in Humans, Human-Shaped World
- AHAndrew Huberman
As long as we're wading into deep water here, let's talk about the really deep water, uh, which is humans.
- BSDr. Beth Shapiro
Okay.
- AHAndrew Huberman
So we have this thing called IVF-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... where people can make embryos and select what are deemed, at this point, healthy versus unhealthy. So people are doing genetic selection in humans-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... through technology, right? People don't really stop too often and think, "Oh, yeah, you know, how is that disrupting the human ecosystem in any different number of ways?" But a few years back, there was a, a guy in China, actually who had been a postdoc at Stanford, who decided to use gene editing to modify the genome of some babies, disrupted the HIV receptor. And there are two stories about this. I don't know which one is true. The one story is that they did it for benevolent reasons to prevent these babies from getting HIV from an, either an infected parent or to just protect them against HIV.
- BSDr. Beth Shapiro
The father was HIV positive.
- AHAndrew Huberman
Mm-hmm. The other story that was running in parallel was that there was, that this, uh, modification, uh, might have some impact on hippocampal or other brain circuit function that might make them hyper intelligent in one dimension, so this was kind of more of a like a eugenics experiment.
- BSDr. Beth Shapiro
Hmm.
- AHAndrew Huberman
That was the idea. And it was very interesting how this emerged, not in the general public. Like, that was interesting in its own right, but there was this short moment of about a week where it wasn't clear if this guy was gonna win a Nobel Prize-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... and be celebrated or was going to be put in prison.
- BSDr. Beth Shapiro
Yeah, I remember this.
- AHAndrew Huberman
Okay.
- BSDr. Beth Shapiro
It was Antonio Regalado-
- AHAndrew Huberman
Yeah
- BSDr. Beth Shapiro
... broke the story about a-
- AHAndrew Huberman
Yeah
- BSDr. Beth Shapiro
... week before the big CRISPR conference.
- AHAndrew Huberman
Yeah. There were these emails that suddenly came out and, and it was very clear, like people were kind of tap dancing around this guy, like, "What's gonna happen to him? Do I want to be associated with this and glean some of the benefit? Or is he going to be demonized? In which case, I want nothing to do with this guy."
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
He's like, "He's, he's blacklisted." It turns out it was the latter, right?
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
And the Chinese government said, "Yeah, we're gonna shut down his lab. He's gonna be punished." I don't know what's happening, if he's running experiments or if he's in prison or what's happening, but, but this was so interesting, right? Because since then, there's been no fewer than four major companies launched for deep sequencing of embryos-
- BSDr. Beth Shapiro
Mm-hmm
- AHAndrew Huberman
... both from IVF, but also non-IVF babies, and I have people coming up to me Saying, "Hey, guess what? We just got to screen these embryos, and we were told which of them is gonna have the highest IQ-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... and which of them is gonna be tallest, and which of them is gonna be this, and which one and that." And so some of these companies are geared towards ruling out disease.
- BSDr. Beth Shapiro
Right.
- 1:38:25 – 1:47:05
Black-Footed Ferrets, Genetic Rescue
- AHAndrew Huberman
Can I ask you about ferrets?
- BSDr. Beth Shapiro
[laughs] You can.
- AHAndrew Huberman
And I also wanna talk about stuff that lives underwater. That ecosystem has all sorts of issues that it needs to deal with. Humans probably have to intervene really quick or-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... we're gonna be in trouble. So ferrets, they're not rats, they're carnivores. Great binocular vision, great hunters, but a few years back, the black-footed ferrets were almost ex- extinct. My understanding, this might be wrong, was that it was that the prairie dog population got out of control when the numbers of black-footed ferrets were, were diminished, and as a consequence, the grasslands were being eaten up like crazy, and that had all sorts of downstream negative consequences. So it was important to reestablish the black-footed ferrets, not just 'cause they're cute. And my understanding is that it was one ferret, Scarface, who sired, like, 300 litters-
- BSDr. Beth Shapiro
[laughs] Yes
- AHAndrew Huberman
... uh, or more, and they were able to resuscitate or at least partially resuscitate the population. So I'm curious which elements of that recollection are false, and also whether or not there's any concern about diversity, given that it was one, uh, one male siring all these, all these litters. Since you get a bunch of kits and they're mating, but-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... mating of close relatives is bad for genomes for reasons that sort of emerged earlier, is you get homozygosity. You get genes that are too similar-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... and then if you have... Most people are, are dominant alleles, uh, you know, where you only need one copy. Okay, uh, that's a separate matter. But what normally m- many mutations you need two copies, recessive alleles, but if you get genes that are very similar-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... b- between brother and sister, you're likely to have two recessive alleles, and you get bad mutations, and you can get deformities and-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... sterilities and a low IQ. It's a very interesting thing that throughout all species inbreeding is bad.
- BSDr. Beth Shapiro
To a point. The, the island foxes, the Channel Island foxes that you talked about, this is a really fascinating example of a population that was so small for such a long time and lived in a pretty steady environment with no predators that they went through that bottleneck where all of those bad mutations were expressed and purged from the population.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And they have almost identical genomes. They have almost no genetic diversity, and they are perfectly healthy.
- AHAndrew Huberman
Wow, okay.
- BSDr. Beth Shapiro
Now, I don't know if something happened to that habitat-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... if they wouldn't be able to survive 'cause there's no diversity of-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... you know, if a disease came in, they would all be susceptible rather than-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... some versus not.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
But-
- AHAndrew Huberman
And that's a very protected, uh, reach-
- BSDr. Beth Shapiro
Super protected
- 1:47:05 – 1:55:09
Dire Wolf; Ecological Modeling, New Technology & Public Fear
- BSDr. Beth Shapiro
Um-
- AHAndrew Huberman
So you pick cool animals to wear. You're like, woolly mammoth, dodo bird, pink pigeon.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
You're like, you know, you guys know how to, you know, uh, get, get-
- BSDr. Beth Shapiro
It's part of, part of it, right? We have to-
- AHAndrew Huberman
Oh, and dire wolf.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
You know. And the dire wolf thing, my understanding is that it was also on the heels of, like, the Game of Thrones popularity, so that, that was, like, a piece. If you weren't gonna make a dragon, you might as well make a, a very large wolf-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... 'cause it has these kind of connotations.
- BSDr. Beth Shapiro
When I was working on the first dire wolf genomes in, way before I was involved with Colossal, but the very first time we published dire wolf DNA, we were desperate to sync the publication with some editor in some, you know, science journal to the Game of Thrones coming out. We were like, "We can get this genome done."
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
"Surely they'll be... They'll want our paper because then they can have some press attention to the dire wolf paper." [laughs]
- AHAndrew Huberman
And?
- BSDr. Beth Shapiro
We never got the DNA finished-
- AHAndrew Huberman
Okay
- BSDr. Beth Shapiro
... in time to do that. It was the, uh, the so poorly preserved. They lived in warmer p- per- parts of the world, and so it was really hard to find samples that had high-quality DNA to be able to get. It, it was a fun project, though.
- AHAndrew Huberman
Were the babies cute?
- BSDr. Beth Shapiro
Yes.
- AHAndrew Huberman
Yeah, okay.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
They didn't come out ferocious, you know?
- BSDr. Beth Shapiro
No, they were extremely-
- AHAndrew Huberman
Just putting a plug in for the di-
- BSDr. Beth Shapiro
... adorable
- AHAndrew Huberman
... for the dire wolf here.
- BSDr. Beth Shapiro
Extremely adorable.
- AHAndrew Huberman
You know?
- BSDr. Beth Shapiro
Yes.
- AHAndrew Huberman
I bet. I bet. Everyone loves a baby animal, environment or not.
- 1:55:09 – 2:01:26
Artificial Wombs; Current Issues, Conservation & Red Wolf
- BSDr. Beth Shapiro
You know, there's a-
- AHAndrew Huberman
You have artificial wombs?
- BSDr. Beth Shapiro
We have one of our-
- AHAndrew Huberman
You realize this is gonna terrify people.
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
I'm a biologist, but okay, so describe to me an artificial womb and what that looks like.
- BSDr. Beth Shapiro
Well, right now we're thinking about, about mice, right?
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
So the idea is if we're going to have hundreds of mammoths, we're not going to get there by having 100 Asian elephants pregnant for 22 months with, with mammoths. We need a way to be able to birth multiple mammoths simultaneously-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... without using elephants. Elephants should be allowed to make elephants.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
Right? And so we'll need to build the technology to do this, but building that technology is also an opportunity to build technology that can really help people and can help other species, but really thinking mostly about people. I have a, a friend who was diagnosed with breast cancer during her pregnancy, and she had to make a decision about not starting the therapy until she gave birth or taking a giant risk with the baby. What if we could just take the baby out and be able to put it in a place and have it completely develop, and then she could start the treatment a couple of months earlier? Or if a baby needs surgery but you can't really do it inside, have a safe way to have that baby come out. These are all technologies that are, will be feasible in the future that are motivated by de-extinction. How crazy is that?
- AHAndrew Huberman
It is wild. One, one of the most incredible things that I've witnessed is a, a NICU.
- BSDr. Beth Shapiro
Wow.
- AHAndrew Huberman
It's a different form of what you're describing, but it's incredible. Like, you go in these places, and it's room upon room, and it's super quiet, and, you know, they try and keep it dark, and there's... I mean, like, these are Artificial wombs, so to speak, right? These are... So preemie babies, and some of which are very preemie. Some have issues and some don't. Some are just early, which is an issue of its own, own kind. But the NICU technology has come a long, long way. It's-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... far from perfect, but that's essentially what you're talking about, right?
- BSDr. Beth Shapiro
Yes. A, a more sophisticated NICU-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... where the, we've learned so much more because of the complementarity of understanding how genes map to phenotypes, and being able to use all of the genetic resources that are available to us from all of the people, and learning about epigenetics, and building this technology that builds on what we understand about the developmental process. I mean, it's a... We are facing a future that I think is really exciting and spectacular. Maybe a little bit scary, but I think as long as we keep talking about it and having conversations about it way before it's possible, we can get to a place that people are comfortable with and people are excited about.
- AHAndrew Huberman
There seems to be a theme lately in my life where people come on this podcast and they're talking about revolutionizing education. We had someone, uh, the principal of Alpha School come on here. Kids spend two hours a day on their iPad learning from an AI tutor that knows exactly what they need to fill every gap in their knowledge.
- BSDr. Beth Shapiro
Cool. I need that. [laughs]
- AHAndrew Huberman
Two hours a day. Then they go, like, learn how to farm, start businesses. It was interesting that public reaction is very divided on that. People either say, "Great," and then other people say, "Oh, yeah, but it costs a lot, so it's only for rich kids." And it turns out they're starting scholarship programs and... But the idea there is to figure out the best way to educate humans-
- BSDr. Beth Shapiro
Right
- AHAndrew Huberman
... and then wick it out to everybody.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
But so- but there has to be this pioneering spirit, and that's always gonna stimulate concern, and there's gonna be the haves and have-nots things in people's minds. I think thinking about your work in, in a different but similar vein where being a pioneer is hard because you have to tolerate people saying, and, and a lot sometimes the assumption that, "Oh, you're doing this just for your own self-interest. It's all financially driven, and what about the, you know, what about the starlings that, you know, need our help right now?" There's always this like what about the things that need our help right now.
- BSDr. Beth Shapiro
Right.
- AHAndrew Huberman
Why are we doing this? And I don't have any great solutions, uh, for you [laughs] on this.
- 2:01:26 – 2:04:31
Science Pioneers; Colossal Public Education
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
Yeah, there's something that I think people need to understand about scientists [laughs] and probably technologists, too, but that's not my, uh, area, which is the person matters. Like, the person doing the work has to be really, really drawn to, almost obsessed with the project. 'Cause you could sort of ask, like, for any scientist. There are a lot of scientists working on kind of pedestrian stuff in my opinion. Used to review a lot of grants for NIH, and you go like, "Eh."
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Sometimes those would get funded, sometimes not. But, but that's the kind of science that certain people do. They wanna turn a crank.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
And then there are certain scientists who really wanna be out on that, like, really cutting edge, and they have to be obsessed with the question, otherwise you get nothing. In the same way that I think Elon's pretty obsessed, I don't know him-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... but with this going to Mars thing. And I don't think he, he's got a bunch of other stuff going on, clearly.
- BSDr. Beth Shapiro
Few things.
- AHAndrew Huberman
But you can't really draw him off target by saying, "Hey, why don't, why aren't you working on curing cancer or building..." I guess he is building flying cars. So the example of musicians to me just works. Like, you, you-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... can't get Metallica to play The Grateful Dead happily. They're just not gonna do it. It's not in their spirit. It's not in their, their soul to do it that way. And so I think that, like, we, we have to accept this about people, and the people who move things forward, like Howard Hughes, the very Howard Hughes, right? He liked his aircraft, right? He liked... You, you can't convince people like, "Oh, you should be saving the coral reefs. Someone else should be saving the coral reefs-
- BSDr. Beth Shapiro
Yeah
- AHAndrew Huberman
... but they need to be obsessed with coral reefs."
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
I mean, I'm stating the obvious, but I think from the inside, it, I relate.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
Um-
- BSDr. Beth Shapiro
Also, people shouldn't feel bad about not being able to do everything. If you think about the amount of time that you have in your life, if you try to do 10 things instead of one thing, you're gonna get way less done.
- AHAndrew Huberman
Oh.
- BSDr. Beth Shapiro
You're not gonna make an impact, so.
- AHAndrew Huberman
It, it's so interesting. People love to tell other people what to do.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
But I will say there are people out there, I know this because of this podcast, th- there are people out there who are enchanted by biology, that are enchanted by what you've told us today, that are excited about these species and can imagine the positive outcome. And some of them are young and some of them are old, but God bless the young ones because they're the ones, it only takes a few of them in a certain area of science to really move things forward, as you know.
- BSDr. Beth Shapiro
Mm-hmm.
- AHAndrew Huberman
So, where are the public education efforts outside of podcasting and whatnot? Like, how many people are at Colossal?
- BSDr. Beth Shapiro
There are about, um, 120 scientists, and then there's, you know, other, other people involved. We have a huge social media team who put a lot of science bits out for the world, uh, targeting different audiences with different types of information. We work with a lot of podcasters, and we work with, um, other teams of people making documentaries and films. We publish papers using the s- traditional old school peer review process. We post some papers on the archive if we think it's important to get the information out faster before peer review. So we're trying th- lots of different methods of communicating. And of course, I go out and talk to people, and I'm a National Geographic Explorer, so I do, I take part in the National G- Geographic Live series. So I've gone and just talked-
- AHAndrew Huberman
Mm, fun
- BSDr. Beth Shapiro
... to communities about, you know, conservation and-
- AHAndrew Huberman
Mm-hmm
- 2:04:31 – 2:13:42
Beth’s Science Origin Story; Dinosaurs
- AHAndrew Huberman
So in junior high, high school, graduate school, were you sitting there thinking, "I'm in a department of zoology at Oxford University-
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
... and there's a picture of some old dude on the wall"? This is wh- how I felt when I went to Cambridge, and I'm like, "That's Darwin's house."
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Or w- it, like, there are two ways to be in that kind of environment. Like, "Whoa, that, that's so-and-so, and there's this history," or was it, "We can do this all much, much better"?
- BSDr. Beth Shapiro
[laughs]
- AHAndrew Huberman
Because I get the sense that you like to break the mold, but I don't wanna, like, kinda lead the witness here. W- so what were you like as a kid, and in graduate school? Were you thinking, "You know, this, this field, this whole zoology thing feels kinda steeped in old stuff, and I wanna break it open"? Or you know, like, maybe just tell us a little bit about your mindset in, in, uh-
- BSDr. Beth Shapiro
Ugh
- AHAndrew Huberman
... these kinds of environments.
- BSDr. Beth Shapiro
My, my origin story. I think I always disappoint people with my science origin story. I went to the University of Georgia as a broadcast journalism major. I had worked for the local TV station in the corner of northwest Georgia where I grew up. I was on air-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... in the mornings. I did local cut-ins on headline news at 24 and 54 after the hour. When I went to the University of Georgia, I was actually the news director of a local radio station that was there, which was not particularly well-aligned with being a freshman at the University of Georgia, we'll just say. I was living in a dorm that had a shared bathroom, and we would... I had to be at work at 4:00 in the morning-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... to write and cut the news so I could be on the drive time show. Do you remember these from the '90s? Like the... Yeah.
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
So I had an opportunity to take a class after my freshman year, and it was an honors program class, and it was geology and archeology. And it was a nine-week class, and we started off on the East Coast and learned about minerals, identifying minerals, and, and the, the sort of coastal dynamics on the coast. Drove across the country, sleeping in national parks, drove up the West Coast, drove back across the country, and learned about the formation of the national parks, the landscape that is the US, right?
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
And I thought to myself as I was watching this, you could see the scars on the landscape from glaciers, and y- we went to all of these archeological sites and anthropological sites and saw the impact of people on the ecosystem and the impact that we had on those people. And I thought, "This is the kind of story that I wanna tell. Maybe I wanna be a science journalist instead of just a regular journalist." The idiocy of people who think they're an expert 'cause they've done something for a few years, I was like, "I already know how to be a journalist. I'll just learn how to be a scientist," right? And so I started taking science classes. I ended up going to Panama, living on a place called Barro Colorado Island and studying parasitoid wasps, and wasn't doing anything related to genetics or really evolution. It was ecology, population ecology, and I met somebody there who was starting up a lab in Edinburgh, and I thought he was really smart and interesting. We put together this proposal of a, a project that I could do as a PhD student where we were gonna study the type of wasp that switches back and forth between inbreeding and outbreeding.
- AHAndrew Huberman
Hmm.
- BSDr. Beth Shapiro
So the question was, is the switch to inbreeding something that is intended to purge your genome of those deleterious alleles-
- AHAndrew Huberman
Mm
- BSDr. Beth Shapiro
... like the Channel Island foxes?
- AHAndrew Huberman
Mm-hmm.
- BSDr. Beth Shapiro
Like, if we inbreed, we'll get rid of all that bad stuff that's accumulated, then we can go back to outbreeding.
- AHAndrew Huberman
It's a pressure test.
- BSDr. Beth Shapiro
Yeah.
- AHAndrew Huberman
Yeah.
- BSDr. Beth Shapiro
So we designed this experiment. I went back to the University of Georgia. I was like, "I'm gonna go to Edinburgh. This is gonna be great. Help me apply for these scholarships," and they said, "Cool," 'cause I couldn't afford to go, you know, overseas for grad school. And they said, "Cool, you can, you can apply, but you have to apply for all of the scholarships that we have for our honors program people together 'cause it's just one big package." So I applied for the Marshall Scholarship-
- AHAndrew Huberman
Mm-hmm
- BSDr. Beth Shapiro
... to go to Edinburgh, and the Rhodes, and I did not get a first-round interview for the Marshall, so ended up not obviously being able to go to Edinburgh, but I got a Rhodes Scholarship, so I ended up at Oxford.
- 2:13:42 – 2:15:36
Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Social Media, Neural Network Newsletter
- AHAndrew Huberman
Thank you for joining me for today's discussion with Dr. Beth Shapiro. To learn more about her work, please see the links in the show note caption. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. And you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast, or guests or topics that you'd like me to consider for the Huberman Lab Podcast, please put those in the comments section on YouTube. I do read all the comments. And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the information on the Huberman Lab Podcast. Again, it's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the menu tab in the top right corner, scroll down to Newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Beth Shapiro. And last, but certainly not least, thank you for your interest in science. [outro music]
Episode duration: 2:15:36
Install uListen for AI-powered chat & search across the full episode — Get Full Transcript
Transcript of episode SFX8FIHFLE4
